StudyFinder
Search Results Within Category "Kidney & Urinary System"
73 Study Matches
Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Study (SAMURAI)
This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Raquibul Hannan
All
18 Years and over
Phase 2
NCT05327686
STU-2023-0448
Inclusion Criteria:
• Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
• Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:
• History/physical examination within 45 days prior to registration
• CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration
• Patients must have IMDC intermediate (1-2 factors) or poor risk disease (>= 3 factors)
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor
• Patient not recommended for or refused immediate cytoreductive nephrectomy
• Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen
• Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging
• Age >= 18
• Karnofsky performance status >= 60 within 45 days prior to registration
• Hemoglobin >= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
• Platelet count >= 50,000/mm^3 (within 45 days prior to registration)
• Absolute neutrophil count (ANC) >= 1500/mm^3 (within 45 days prior to registration)
• Calculated (Calc.) creatinine clearance >= 30 mL/min (within 45 days prior to registration)
• For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR >= 30 mL/min/1.73m^2 will be considered adequate
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) (within 45 days prior to registration)
• Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =< 3 x upper limit of normal (ULN) or < 5 x ULN if hepatic metastases present (within 45 days prior to registration)
• Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
• The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
• Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment
• Patients with untreated or unstable brain metastases or cranial epidural disease
• Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
• Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor
• Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated > 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)
• Severe, active comorbidity defined as follows:
• Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
• Active tuberculosis (purified protein derivative [PPD] response without active tuberculosis [TB] is allowed)
• Uncontrolled hypertension (systolic blood pressure [BP] > 190 mmHg or diastolic BP > 110 mmHg)
• Major surgery requiring hospital admission ≤ 28 days prior to registration.
• Any serious (requiring hospital stay or long-term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration
• Any arterial thrombotic (ST elevation myocardial infarction [STEMI], non-ST elevation myocardial infarction [NSTEMI], cerebrovascular accident [CVA], etc) events within 180 days prior to registration
• Active New York (NY) Heart Association class 3-4 heart failure symptoms
• Moderate or severe hepatic impairment (Child-Pugh B or C)
• Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis > 30 days prior to registration is allowed)
• Unstable cardiac arrhythmia within 180 days prior to registration
• History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration
• History of or active inflammatory bowel disease
• Malabsorption syndrome within 45 days prior to registration
• Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =< 45 days prior to registration
Biological: Avelumab, Drug: Axitinib, Drug: Cabozantinib, Biological: Ipilimumab, Drug: Lenvatinib, Biological: Nivolumab, Biological: Pembrolizumab, Radiation: Stereotactic Ablative Radiotherapy
Metastatic Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Kidney, Stage III Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma
UT Southwestern
A Study to Evaluate Safety, Efficacy of FF-10832 in Combo With Pembrolizumab in Urothelial & Non-small Cell Lung Cancer
To confirm a recommended Phase 2 dose (RP2D) of FF-10832 (Gemcitabine Liposome Injection) given intravenously Day 1 of a 21-day cycle, in combination with 200 mg pembrolizumab given intravenously Day 1 of the same 21-day cycle, for treatment of advanced urothelial and non-small cell lung cancer
Call 833-722-6237
canceranswerline@utsouthwestern.edu
John Lohrey
ALL
18 Years and over
PHASE2
NCT05318573
STU-2023-0065
Inclusion Criteria:
• Written informed consent is provided by patient or legally acceptable representative;
• Age ≥ 18 years;
• Patient populations:
• In the Safety Run-in, patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have disease progression after treatment with standard therapies for metastatic disease that are known to confer clinical benefit, or are intolerant to treatment or refuse standard treatment will be enrolled in therapy
• In Expansion Phase, patient must have urothelial or NSCLC, and have failed prior anti-PD-1 or anti-PD-L1
• Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
• Eastern Cooperative Oncology Group performance status of 0 to 1
• Life expectancy of ≥ 3 months
Exclusion Criteria:
• Positive urine pregnancy test within 72 hours prior to treatment
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (or 5 half-lives, whichever is shorter) prior to treatment;
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), AND was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event;
• Has received prior radiotherapy within 2 weeks of start of study treatment.
• For patients with NSCLC:
• Patients who have received radiation therapy to the lung that is \>30 Gy within 6 months of the first dose of trial treatment are excluded;
• Patients with mutations (e.g., EGFR mutations or ALK gene rearrangements) will be excluded unless they have been previously treated with all specific targeted therapies.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
• Has had an allogeneic tissue /solid organ transplant.
DRUG: Pembrolizumab, DRUG: FF-10832
Advanced Urothelial Carcinoma, Lung/Thoracic, Urinary Bladder, Advanced Non Small Cell Lung Cancer
UT Southwestern
Neoadjuvant Lenvatinib and Pembrolizumab for IVC Tumor Thrombus
This study will be evaluating safety and efficacy of the combination of lenvatinib and pembolizumab neoaadjuvant therapy prior to surgical resection of locally advanced renal cell carcinoma with IVC tumor thrombus.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vitaly Margulis
ALL
18 Years and over
PHASE2
NCT05319015
STU-2021-1240
Inclusion Criteria:
* Male/female participants who are at least 18 years of age
* Have histologically confirmed cT3-4,N0-1,M0-1 (clinical stage III-IV) diagnosis of renal cell carcinoma (any subtype) with level II-IV inferior vena cava tumor thrombus
* The primary tumor and thrombus may be assessed to be resectable or unresectable at the time of enrollment
* Male participants: A male participant must agree to use a protocol-approved contraception during the 120 day neoadjuvant treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period.
* Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the protocol-approved contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment. * The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. * Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention. * Have adequate organ function as defined in the following table. Specimens must be collected within 10 days prior to the start of study intervention. * Absolute neutrophil count (ANC): ≥1500/µL * Platelets: ≥100 000/µL * Hemoglobin: ≥9.0 g/dL or ≥ 5.6 mmol/La * Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl): ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN * Total bilirubin: ≤1.5 ×ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels \>1.5 × ULN * AST (SGOT) and ALT (SGPT): ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) * International normalized ratio (INR) OR prothrombin time (PT) OR Activated partial thromboplastin time (aPTT): ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants * ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. * Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. * Creatinine clearance (CrCl) should be calculated per institutional standard. * Note: This includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.
Exclusion Criteria:
* A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
* Has received prior systemic anti-cancer therapy including investigational agents prior to allocation.
* Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
* Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. COVID-19 vaccines are permitted provided they are not live attenuated vaccines.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Has a known additional malignancy that is progressing or has required active treatment within the past year. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer, bladder in situ) that have undergone potentially curative therapy are not excluded.
* Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
* Has more than three different sites of metastatic renal cell carcinoma.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and lenvatinib and/or any of its excipients.
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy.
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
* Has had an allogenic tissue/solid organ transplant.
* Has prolongation of QTcF interval to \>480 ms.
* Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
* Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted
* Has urine protein ≥1 g/24 hours. Note: Participants with proteinuria ≥2+\>1+ (≥100 mg/dL) on urine dipstick testing (urinalysis) will undergo 24-hour urine collection for quantitative assessment of proteinuria.
* Uncontrolled blood pressure (Systolic BP\>140 mmHg or diastolic BP \>90 mmHg) in spite of an optimized regimen of antihypertensive medication. DRUG: Neoadjuvant Lenvatinib, DRUG: Neoadjuvant Pembrolizumab, PROCEDURE: Radical nephrectomy, IVC thrombectomy, retroperitoneal lymph node dissection, DRUG: Adjuvant Pembrolizumab
Renal Cell Carcinoma, Cardiovascular, Kidney
Renal Cell Carcinoma, IVC tumor thrombus, Neoadjuvant therapy, Immunotherapy, Nephrectomy
UT Southwestern
Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
This phase I/II trial studies how well tiragolumab and atezolizumab works when given to children and adults with SMARCB1 or SMARCA4 deficient tumors that have either come back (relapsed) or do not respond to therapy (refractory). SMARCB1 or SMARCA4 deficiency means that tumor cells are missing the SMARCB1 and SMARCA4 genes, seen with some aggressive cancers that are typically hard to treat. Immunotherapy with monoclonal antibodies, such as tiragolumab and atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
12 Months and over
PHASE1
NCT05286801
STU-2022-0879
Inclusion Criteria:
* Patients must be \>= 12 months of age at the time of study enrollment. For part A, patients must be \< 18 years old at enrollment. For part B, there is no upper age limit
* The Part B (phase 2) cohorts will initially open concurrently with the part A but will only enroll patients at least 18 years of age. Patients \< 18 years of age will be included in the part B cohorts only after the tiragolumab monotherapy dose has been assessed to be safe in the part A portion
* Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional immunohistochemistry (IHC) or molecular confirmation of a pathologic SMARCB1 (INI1) or SMARCA4 loss or mutation from a Clinical Laboratory Improvement Act (CLIA) certified lab with the following disease histologies:
* Renal medullary carcinoma
* Malignant rhabdoid tumor (extra-CNS)
* Atypical teratoid rhabdoid tumor (CNS)
* Poorly differentiated chordoma
* Epithelioid sarcoma
* Other SMARCB1 or SMARCA4 deficient tumors
* Note: Molecular studies will only be used if IHC is equivocal or cannot be performed. Documentation of the institutional IHC or molecular testing must be uploaded via the RAVE system
* Part A: Patients must have either measurable or evaluable disease Part B: Patients must have either measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors
* Note: See protocol for specific exclusion for patients with CNS primary or metastatic disease
* Patients must have relapsed, refractory disease or newly diagnosed disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (Karnofsky/Lansky score of \>= 50). Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/Anticancer Agents on the COG website: https://www.cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/TableOfMyelosuppressiveAnti-CancerAgents.pdf
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell infusions (with or without total-body irradiation \[TBI\]):
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* External radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 90 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, iodine I 131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have had prior TIGIT targeting therapy
* Patients must not have received prior therapy with an anti- PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (i.e. OX-40, CD137)
* Patients must not have received live/attenuated vaccine within 30 days of first dose of treatment
* Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
* The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are acceptable
* Treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha \[TNF-alpha\] agents) must have concluded \>= 14 days prior to study enrollment
* For patients with solid tumors without known bone marrow involvement
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (must be performed within 7 days prior to enrollment)
* For patients with solid tumors without known bone marrow involvement
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (must be performed within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
* A creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment):
* Age; Maximum Serum Creatinine (mg/dL)
* 1 to \< 2 years; Male: 0.6; Female: 0.6
* 2 to \< 6 years; Male: 0.8; Female: 0.8
* 6 to \< 10 years; Male: 1; Female: 1
* 10 to \< 13 years; Male: 1.2; Female: 1.2
* 13 to \< 16 years; Male: 1.5; Female: 1.4
* \>= 16 years; Male: 1.7; Female: 1.4 OR- a 24 hour urine creatinine clearance \>= 70 mL/min/1.73 m\^2 (must be performed within 7 days prior to enrollment) OR- a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) (must be performed within 7 days prior to enrollment)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
* Patients with known Gilbert disease: Total bilirubin =\< 3 x ULN
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (must be performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
* Albumin \>= 2 g/dL (must be performed within 7 days prior to enrollment)
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] v5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* International normalized ratio (INR) =\< 1.5 (must be performed within 7 days prior to enrollment)
* Serum amylase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Serum lipase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Grade 1 or lower calcium level
* Note: can have history of hypercalcemia as long as controlled and asymptomatic
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in female patients of childbearing potential. Female patients of childbearing potential are defined as those who are past the onset of menarche and are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, complete hysterectomy) or post-menopausal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of therapy and at least 90 days after final dose of tiragolumab and 150 days after final dose of atezolizumab, whichever is later. Abstinence is an acceptable method of birth control.
* It is not known if atezolizumab or tiragolumab are present in breast milk; however, IgG immunoglobulins are found in milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during therapy and for at least 150 days after the last dose of atezolizumab and 90 days after the last dose of tiragolumab, whichever is later
* Concomitant medications:
* Corticosteroids:
* Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
* The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are acceptable
* Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
* Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible
* Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) during study treatment because these agents could potentially alter the efficacy and safety of study treatments would not be eligible
* Patients must not have a known hypersensitivity to any component of tiragolumab or atezolizumab injection
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation
* Patients who have undergone allogeneic bone marrow or allogeneic cell transplant are not eligible
* Patients with CNS metastases from non-CNS primary tumors are not eligible unless CNS metastases have been previously treated and sequential imaging shows no evidence for active disease in the CNS.
* Patients with primary CNS tumors (including ATRT) with involvement of the brainstem are not eligible. Note: Patients with ATRT with M0-M4 disease without involvement of the brain stem are allowed to participate
* Patients must not have active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are not excluded. Replacement therapy (e.g. thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and these patients are eligible
* Patients who have active immune deficiency are not eligible
* Patients who have known active tuberculosis are not eligible
* Hepatitis B or C infection:
* Patients \< 18 years old at enrollment, who have known hepatitis B or C
* Patients \>= 18 years old at enrollment with:
* Positive hepatitis B surface antigen (HBsAg), OR
* Positive total hepatitis B core antibody (HBcAb) who have a quantitative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \>= 500 IU/mL, OR
* Positive hepatitis C virus (HCV) antibody with a positive HCV ribonucleic acid (RNA) test
* Note: For adults (\>= 18 years old at enrollment), hepatitis B serology testing is required to determine eligibility. The HBV DNA test is required only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. For adults (\>= 18 years old at enrollment), hepatitis C serology testing is required to determine eligibility. The HCV RNA test is required only for patients who have a positive HCV antibody test
* Patients who have a known, recent Epstein-Barr virus (EBV) infection or known history of chronic, active infection are not eligible
* Patients who have history of or active human immunodeficiency virus (HIV) are not eligible except patients who are stable on anti-retroviral therapy, have a CD4 count \>= 200/uL, and have an undetectable viral load
* Patients who have significant cardiovascular disease (such as New York Heart Association class III or IV congestive heart failure, myocardial infarction, or cerebrovascular accident) within 3 months prior to study enrollment, unstable arrhythmia, or unstable angina are not eligible
* Patients who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to study enrollment, or the anticipation of the need for a major surgical procedure during the study are not eligible
* Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or known active pneumonitis are not eligible. History of radiation pneumonitis in the radiation field is permitted
* Patients who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) are not eligible. Patients with indwelling catheters (e.g., PleurX) are allowed
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible BIOLOGICAL: Atezolizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, OTHER: Fludeoxyglucose F-18, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Tiragolumab, PROCEDURE: X-Ray Imaging
Epithelioid Sarcoma, Recurrent Malignant Solid Neoplasm, Refractory Malignant Solid Neoplasm, Rhabdoid Tumor, Recurrent Rhabdoid Tumor, Refractory Rhabdoid Tumor, Kidney Medullary Carcinoma, Malignant Solid Neoplasm, Bones and Joints, Soft Tissue, Atypical Teratoid/Rhabdoid Tumor, Poorly Differentiated Chordoma, Recurrent Atypical Teratoid/Rhabdoid Tumor, Recurrent Chordoma, Recurrent Epithelioid Sarcoma, Recurrent Kidney Medullary Carcinoma, Refractory Atypical Teratoid/Rhabdoid Tumor, Refractory Chordoma, Refractory Epithelioid Sarcoma, Refractory Kidney Medullary Carcinoma
Children’s Health
Enfortumab Vedotin and Pembrolizumab in People With Bladder Cancer
This study will test whether enfortumab vedotin combined with pembrolizumab is an effective treatment for people with bladder cancer (urothelial carcinoma) involving the lymph nodes who are going to have surgery to remove their cancer (cystectomy). The researchers will look at whether treatment with enfortumab vedotin and pembrolizumab before surgery can get rid of cancer within the lymph nodes. They will also try to find out if this combination of drugs is effective at shrinking participants' cancer before their surgery. The researchers think that a combination of enfortumab vedotin and pembrolizumab may help people with this disease because both drugs are designed to help the immune system attack and kill cancer cells. The researchers think the drugs may be more effective if given in combination rather than on their own.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE2
NCT05239624
STU-2023-0105
Inclusion Criteria:
* Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of muscle invasive bladder cancer (previously known as transitional cell) carcinoma (i.e., cancer of the bladder, renal pelvis, ureter, or urethra)
* Clinical Stage T2-T4, N1-N3, M0 OR cT1, N2-N3, M0
* Pathology:
* Representative urothelial carcinoma FFPE tumor specimens (tumor blocks or 20 unstained slides). Patients with \< 20 slides may be enrolled after discussion with the principal investigator.
* Muscle invasive urothelial carcinoma of the bladder histologically confirmed at the enrolling institution from TURBT. (Urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed provided the extent of disease is confirmed via imaging and/or EUA.)
* Evidence of urothelial carcinoma from FNA of lymph node OR lymphadenopathy suspicious for nodal disease on cross-sectional imaging, MRI, or u/s.
* Node positivity for eligibility will be defined as imaging read with suspicious lymph node ≥ 1.0 cm in the short axis, with biopsy, as documented by the radiologist at the treating center. While biopsy to confirm lymph node involvement is preferred, patients without biopsy proven urothelial carcinoma in lymph nodes may be enrolled if imaging shows a lymph node ≥ 1.0 cm in the short axis, and with confirmation from the study principal investigator.
* Deemed medically appropriate for radical cystectomy with treatment response achieved, as per MSK or participating site Attending Urologic Oncologist
* Platinum eligible and ineligible patients are permitted on study
* No prior treatments for muscle invasive or metastatic urothelial carcinoma
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
* Estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m2 using the CKD-EPI equation: eGFR = 141 x min(Scr/k, 1)a x max (Scr/k, 1)-1.209 x 0.993Age x 1.018 \[if female\] x 1.159 \[if black\]
°Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1
* Be willing and able to provide written informed consent for the trial
* Contraception requirements:
• Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days following the last dose of treatment, corresponding to time needed to eliminate any study treatment(s) (e.g. 5 terminal half-lives for pembrolizumab and enfortumab vedotin) plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: i. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR ii. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least \[90 days (corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and enfortumab vedotin) plus 30 days (a menstruation cycle)\] after the last dose of study treatment. * Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 14 days prior to the start of study treatment either prior to consent or at the study screening visit. * Hematological * Absolute neutrophil count (ANC) ≥1500/μL * Platelets ≥100 000/μL * Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La * Renal °Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) GFR or CrCl of ≥ 30 mL/min * Hepatic * Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN * AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN * Coagulation °International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. b eGFR as calculated by the CKD-EPI equation can be used in place of the creatinine clearance Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies
Exclusion Criteria:
* Evidence of NYHA functional class III or IV heart disease
* Any of the following within 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
* On-going cardiac dysrhythmias of NCI CTCAE Version 5.0 grade ≥ 2. However, stable atrial fibrillation controlled medically or with a device (i.e. pacemaker) or prior ablation is allowed
* Pre-existing sensory grade ≥ 2 neuropathy
* Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure aside from cystectomy during the course of the study. Transurethral resection or other urinary tract diagnostic procedures, excisional biopsy, IR-guided biopsy, or MEDIPORT placement are NOT defined as major surgical procedures.
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
* A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
* Is currently enrolled in another therapeutic trial. Patients cannot receive concurrent treatment on another clinical trial; Patients are allowed to enroll on supportive care trials or non-treatment trials (e.g. QOL, dietary survey studies) concurrently
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to allocation.
* Prior treatment with an antibody drug conjugate for bladder cancer directed therapy
* Prior systemic chemotherapy (prior intravesical therapy is allowed)
* Prior radiation therapy to the bladder
* Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
* Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. 1. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Administration of killed vaccines is allowed. COVID-19 vaccination is permitted.
°Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.
* Has receieved intravesical bacillus Calmette-Guerin (BCG) within 4 weeks before Cycle 1, Day 1 14.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Has a history of poorly controlled human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) related illness. Patients with a history of an aids-defining opportunistic infection within the last 12 months or who are on prophylactic antimicrobials related to underlying HIV are not eligible. Patients with a history of HIV and a CD4 T cell count of ≥350 are eligible to enroll in this study with the approval of the study PI.
* Subjects with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to \<8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
* Has a history of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, systemic vasculitis, or glomerulonephritis.
* Patients with history of autoimmune related hypothyroidism on stable dose of thyroid replacement hormone may be eligible for this study
* Patients with controlled Type I diabetes mellitus on a stable dose of insulin may be eligible for this study
* Has a history of idiopathic pulmonary fibrosis, pneumonitis/interstitial lung disease that requires steroids or has current pneumonitis/interstitial lung disease (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
* Patients with active hepatitis B virus (HBV, chronic or acute, defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C antibody
* Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[HBc Ab\] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to Cycle 1, Day 1 and confirmed to be negative.
* Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
* Active tuberculosis or BCG infection
* Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
* Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1. Abnormal urinalysis does not constitute signs/symptoms of infection unless urine culture obtained at screening grows ≥ 100,000 colonies of bacteria.
* Therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1
* Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
* Patients receiving antibiotics for active infection are not eligible
* Prior allogeneic stem cell or solid organ transplant
* AEs from prior anticancer therapy that have not resolved to Grade ≤ 1 except for alopecia
* Patients with a history of or active bone marrow disorders expected to interfere with study therapy (e.g. acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma)
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; and inherited liver disease
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
* Patients with active keratitis or history of corneal ulcers are excluded
* Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
* Rash must cover less than 10% of body surface area (BSA)
* Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
* No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
* Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-ofcare management (e.g. prostate cancer with Gleason score ≤ 7, and prostate-specific antigen \[PSA\] ≤ 10 mg/mL, etc). DRUG: Enfortumab vedotin, DRUG: Pembrolizumab
Urothelial Carcinoma, Gall Bladder, Urinary Bladder
Locally Advanced and/or Node Positive, Enfortumab vedotin, Pembrolizumab, Clinical Stage T2-T4, N1-N3, M0 OR cT1, N2-N3, M0, 21-316
UT Southwestern
Study of XL092 in Combination With Immuno-Oncology Agents in Subjects With Solid Tumors (STELLAR-002)
This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, PK, preliminary antitumor activity, and effect of biomarkers of XL092 administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) in subjects with advanced solid tumors. In the Expansion Stage, the safety and efficacy of XL092 as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
All
18 Years and over
Phase 1
NCT05176483
STU-2022-0177
Inclusion Criteria:
• Cytologically or histologically confirmed solid tumor that is unresectable, locally advanced or metastatic.
• Dose-Escalation Cohorts: Subjects with a solid tumor that is unresectable or metastatic and for which life-prolonging therapies do not exist or available therapies are intolerable or no longer effective.
• Expansion Cohort 1 (ccRCC): Subjects with unresectable advanced or metastatic RCC with a clear cell component who have not received prior systemic therapy.
• Note: Prior non-VEGF targeted adjuvant or neoadjuvant is allowed if disease recurrence occurred 6 months after the last dose.
• Expansion Cohort 2 (ccRCC): Subjects with unresectable advanced or metastatic RCC with a clear cell component.
• Must have radiographically progressed after a combination therapy consisting of a PD-1/PD-L1 targeting mAb with a VEGFR-TKI or a PD-1 targeting mAb with a CTLA-4 mAb as the preceding line of therapy.
• Must have received no more than one prior systemic anticancer therapy for unresectable advanced or metastatic renal cell carcinoma.
• Expansion Cohort 3 (mCRPC): Men with metastatic adenocarcinoma of the prostate.
• Must have progressed during or after one NHT given for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (CSPC), M0 CRPC, or mCRPC.
• Expansion Cohort 4 (UC, ICI-naive): Subjects with histologically confirmed unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).
• Must have progressed during or after prior first-line platinum-based combination therapy, including subjects who received prior neoadjuvant or adjuvant platinum-containing therapy with disease recurrence < 12 months from the end of last therapy.
• Must have received no more than 1 prior line of systemic anticancer therapy for unresectable, locally advanced or metastatic disease.
• Expansion Cohort 5 (UC, ICI-experienced): Subjects with histologically confirmed unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including the renal pelvis, ureter, urinary bladder, or urethra).
• Must have progressed during or after prior PD-1/PD-L1 targeting ICI therapy given as monotherapy, combination therapy, maintenance therapy or adjuvant therapy.
• Must have received no more than 2 prior lines of systemic anticancer therapy for unresectable advanced or metastatic disease.
• Expansion Cohort 6 (nccRCC): Subjects with unresectable advanced or metastatic nccRCC of the following subtypes: Papillary RCC (any type), unclassified RCC, and translocation-associated. Among the eligible histologic subtypes, sarcomatoid features are allowed.
• No prior systemic anticancer therapy is allowed except adjuvant or neoadjuvant therapy if disease recurrence occurred at least 6 months after the last dose.
• Expansion Cohort 7 (HCC): Subjects with inoperable locally advanced, recurrent, or metastatic HCC that is not amenable to curative treatment or locoregional therapy.
• Expansion Cohort 8 (NSCLC): Subjects with Stage IV non-squamous NSCLC with positive PD-L1 expression (tumor proportion score [TPS] 1-49%) and without prior systemic anticancer therapy for metastatic disease.
• Expansion Cohort 9 (NSCLC): Subjects with Stage IV non-squamous NSCLC who have radiologically progressed following treatment with one prior immune checkpoint inhibitor (anti-PD-1 or anti-PD-L1) for metastatic disease.
• Expansion Cohort 10 (CRC): Subjects with histologically confirmed unresectable, locally advanced, or metastatic adenocarcinoma of the colon or rectum.
• Expansion Cohort 11 (HNSCC): Subject with inoperable, refractory, recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx. PD-L1 combined positive score (CPS) ≥1.
• For all Expansion Cohorts except Cohort 3: Measurable disease per RECIST 1.1 as determined by the Investigator.
• For expansion cohorts only: Archival tumor tissue material, if available, or fresh tumor tissue if it can be safely obtained.
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from AE(s) related to any prior treatments unless AE(s) are deemed clinically nonsignificant by the Investigator and/or stable on supportive therapy.
• Karnofsky Performance Status (KPS) ≥ 70%.
• Adequate organ and marrow function.
• Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception.
• Female subjects of childbearing potential must not be pregnant at screening.
Exclusion Criteria:
• For all Dose-Escalation cohorts: Prior treatment with XL092. For all Expansion Cohorts: Prior treatment with XL092, nivolumab, ipilimumab or relatlimab with the following exceptions: Prior PD-1/PD-L1, LAG-3 and CTLA-4 targeting therapy for locally advanced or metastatic disease is allowed for Cohort 2 (ccRCC), Cohort 5 (UC), Cohort 9 (NSCLC).
• For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• For Cohort 3 (mCRPC): Receipt of abiraterone within 1 week; cyproterone within 10 days; or receipt of flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen receptor inhibitors within 2 weeks before first dose of study treatment.
• For all Dose-Escalation Cohorts and Expansion Cohort 2 (ccRCC), Cohort 3 (mCRPC), Cohort 5 (UC), Cohort 9 (NSCLC) and Cohort 10 (CRC): Receipt of any type of anticancer antibody or systemic chemotherapy within 4 weeks before first dose of study treatment.
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
• Prior external radiation therapy for bone metastasis within 2 weeks, for other tumor sites within 4 weeks, and prior radium-223 therapy within 6 weeks before first dose of study treatment, unless otherwise specified.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy (including radiosurgery) or surgically removed and stable for at least 4 weeks before first dose of study treatment.
• Concomitant anticoagulation with oral anticoagulants and platelet inhibitors.
• Administration of a live, attenuated vaccine within 30 days prior to enrollment.
• Uncontrolled, significant intercurrent or recent illness.
• Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment.
• Subjects with inadequately treated adrenal insufficiency.
• Pregnant or lactating females.
• Any other active malignancy within two years before first dose of study treatment, except for locally curable cancers that have been apparently cured such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• For Cohort 2 (ccRCC, 2L): Receipt of a prior triplet therapy including a VEGFR-TKI, a PD1 targeting mAb, and a CTLA-4 mAb.
• For Cohort 3 (mCRPC): Receipt of a taxane-based chemotherapy for mCRPC.
• For Cohort 4 (UC, ICI-naïve): Subjects who have had recurrence within the 6 months of completing adjuvant anti-PD-(L)1 treatment.
• For Cohort 6 (nccRCC, 1L): Subjects with chromophobe, renal medullary carcinoma, or pure collecting duct nccRCC.
• For Cohort 7 (HCC):
• Documented hepatic encephalopathy (HE) within 6 months before randomization (see Section 6.5.2 for a case definition of HE).
• Clinically meaningful ascites (ie, ascites requiring paracentesis or escalation in diuretics) within 6 months before randomization.
• Subjects who have received any local anticancer therapy including surgery, PEI, RFA, MWA, transarterial chemoembolization (TACE), or transarterial radioembolization (TARE) within 28 days prior to randomization.
• Subjects with known fibrolamellar carcinoma, sarcomatoid HCC, or mixed hepatocellular cholangiocarcinoma
• For Cohort 10 (CRC, 2L+): Receipt of prior therapy with regorafenib and/or TAS-102.
• For Cohort 11 (HNSCC): Primary tumor site of the nasopharyngeal area.
• For Cohorts 1 (ccRCC, 1L), 2 (ccRCC, 2L), 4, 5 (UC), 7 (HCC), 8 (NSCLC 1L PD-L1 low), 9 (NSCLC, 2L+), 10 (CRC, MSS, 2L+), and 11 (HNSCC):
• Troponin T (TnT) or I (TnI) > 2 × institutional ULN. Note: Additional Inclusion and Exclusion criteria may apply.
Drug: XL092, Drug: Nivolumab, Drug: Ipilimumab, Drug: Nivolumab, Drug: Nivolumab, Drug: Nivolumab + Relatlimab
Non-Small Cell Lung Cancer, Hepatocellular Carcinoma, Colorectal Cancer, Renal Cell Carcinoma, Head and Neck Squamous Cell Carcinoma, Urothelial Carcinoma, Solid Tumor, Kidney, Prostate, Urinary Bladder, Metastatic Castration-resistant Prostate Cancer
UT Southwestern
Pediatric Radiation Oncology With Movie Induced Sedation Effect (PROMISE)
PROMISE (Pediatric Radiation Oncology with Movie Induced Sedation Effect) is an interactive incentive-based movie system that integrates with a video surveillance gating module (VisionRT) as an alternative sedation solution for pediatric patients undergoing radiation treatment (RT). This single-arm, open label, single-center phase II clinical trial is to implement PROMISE for all children ages 3-11 who are planned to undergo RT at the institution. The primary goal is to decrease the total number of pediatric patients who require general anesthesia through the use of PROMISE, with secondary goals being to assess the impact that PROMISE has on patient/family anxiety and quality of life, treatment time and clinical efficiency, and overall cost. The investigators hypothesize that PROMISE will lead to a reduction in the percentage of patients ages 3-7 who require general anesthesia use from 70% (historical control) to 30%.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Kiran Kumar
ALL
3 Years to 11 Years old
PHASE2
NCT05148078
STU-2021-1005
Inclusion Criteria:
• Planned to undergo radiation treatment
• Age 3-11 years
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at screening
• Parents or guardians with the ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Subjects with documented medical behavior conditions or other conditions necessitating anesthesia use
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
• Subjects whose parents opt to not include them (the subject) in the clinical trial.
OTHER: PROMISE (Pediatric Radiation Oncology with Movie Induced Sedation Effect)
Multiple Myeloma, Pediatric Cancer, Brain and Nervous System, Eye and Orbit, Bones and Joints, Kidney, Lip, Oral Cavity and Pharynx, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Rectum, Thyroid, Leukemia, Other, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Soft Tissue
radiotherapy
UT Southwestern; Children’s Health
Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung
This phase II/III trial compares the effect of immunotherapy with atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone for the treatment of poorly differentiated extrapulmonary (originated outside the lung) neuroendocrine cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). The other aim of this trial is to compare using atezolizumab just at the beginning of treatment versus continuing it beyond the initial treatment. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. Giving atezolizumab in combination with a platinum drug (cisplatin or carboplatin) and etoposide may work better in treating patients with poorly differentiated extrapulmonary neuroendocrine cancer compared to standard therapy with a platinum drug (cisplatin or carboplatin) and etoposide alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
ALL
18 Years and over
PHASE2
NCT05058651
STU-2023-0750
Inclusion Criteria:
* Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC)
* Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator
* Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and non-measurable lesions must be assessed by CT scan with IV contrast of the chest/abdomen/and pelvis (or CT chest without contrast and MRI abdomen/pelvis with gadolinium contrast, if contraindication to CT iodinated contrast) within 28 days prior to registration. While may be used for routine clinical evaluation, PET scans and bone scans alone are not acceptable for disease assessment while participating in this study. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) if clinically indicated within 28 days prior to registration. Note: Brain imaging is not required in participants without known and/or clinical concern for brain metastases. Participants with asymptomatic central nervous system (CNS) metastases are eligible if one or more of the following apply:
* Participants who have received treatment for brain metastases must have:
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* Discontinued all corticosteroids at least 14 days prior to registration
* Participants with treatment-naive brain lesions must have:
* No lesion measuring \> 2.0 cm in size in any axis
* MRI brain or CT head with contrast (if there is contraindication to MRI brain) demonstrating no evidence for mass effect, edema, or other impending neurological compromise within 28 days prior to registration
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* No need for \> 2 mg of dexamethasone (or equivalent of \> 10 mg prednisone) per day at time of registration
* Participants must not have symptomatic central nervous system (CNS) metastases
* Participants must not have known or suspected leptomeningeal disease
* Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinum-based therapy +/- radiation +/- surgery provided that all therapy was completed \>= 6 months prior to registration
* Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study
* Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed \>= 24 weeks prior to registration and participants have recovered from all prior toxicities to =\< grade 1.
* Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least 12 months prior to study registration
* Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 \[IL-2\] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to registration
* Participants must not have had history of known severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, including to Chinese hamster ovary cell products or to any component of the atezolizumab formulation, cisplatin, carboplatin, or etoposide
* Participants must not be on active systemic therapy for another cancer with the exception of hormonal therapy including androgen deprivation therapy (e.g., gonadotropin-releasing hormone \[GnRH\] agonists or antagonists), which can be continued while participants are receiving protocol therapy. Use of enzalutamide or apalutamide is permitted after completion of chemotherapy and must be held during chemotherapy for participants receiving prior to enrollment. Use of darolutamide is permitted during chemotherapy. Glucocorticoid-containing regimens, including abiraterone, are not permitted.
* Participants must be \>= 18 years of age
* Participants must have a Zubrod performance status of =\< 2 within 28 days prior to registration
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9 /L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Hemoglobin \>= 9.0 g/dl (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Platelet count \>= 100 x 10\^9/L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum total bilirubin =\< 1.5 x ULN (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Adequate renal function as defined by any 1 of the following: 1) Measured creatinine clearance (CL) \> 50 mL/min OR 2) Calculated creatinine CL \> 50 mL/min by the Cockcroft-Gault formula OR by 24-hour urine collection for determination of creatinine clearance (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Participants must not have uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN) within 14 days prior to registration. Participants who have asymptomatic hypercalcemia are eligible provided that medical therapy to treat the hypercalcemia is planned
* Participants must not have a diagnosis of immunodeficiency nor be receiving systemic steroid therapy (equivalent of \> 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 14 days prior to registration
* Participants must not have active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:
* Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
* Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* Rash must cover \< 10% of body surface area
* Disease is well controlled at baseline and requires only low-potency topical corticosteroids
* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
* Participants must not have history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Participants must not have significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction within 3 months prior to registration, unstable arrythmias, or unstable angina
* Participants must not have had a major surgical procedure other than for diagnosis within 28 days prior to registration. Participant must not plan to receive a major surgical procedure during the course of protocol treatment. NOTE: Patient port placement is not considered a major surgery
* Participants must not have severe infections (i.e., Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>= 2) at time of registration, including but not limited to hospitalization for complications for infection, bacteremia, or severe pneumonia
* Participants must not have known active tuberculosis
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load, with testing performed as clinically indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load, with testing performed as clinically indicated
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months of registration
* Participants must not have prior allogeneic bone marrow transplantation or solid organ transplant
* Participants must not have received administration of a live, attenuated vaccine (e.g., FluMist \[registered trademark\]) within 28 days prior to initiation of study treatment, during treatment with atezolizumab, and not plan to receive for 5 months after the last dose of atezolizumab
* Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method (with details provided as a part of the consent process) during the treatment period and for 5 months after the final dose of atezolizumab. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines BIOLOGICAL: Atezolizumab, PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Etoposide, PROCEDURE: Magnetic Resonance Imaging, OTHER: Patient Observation
Brain and Nervous System, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Thyroid, Urinary Bladder, Other Hematopoietic, Small Intestine, Soft Tissue, Advanced Extrapulmonary Neuroendocrine Carcinoma, Metastatic Extrapulmonary Neuroendocrine Carcinoma, Recurrent Extrapulmonary Neuroendocrine Carcinoma, Unresectable Extrapulmonary Neuroendocrine Carcinoma
UT Southwestern
Effect of SGLT2i on Cardiovascular Biomarkers in Patients With Type 2 Diabetes and CKD Stage 3b-4
This is a prospective, observational study to assess the effect of SGLT2 inhibitors on surrogate markers of kidney and cardiovascular health in patients with stage 3b and 4 chronic kidney disease (CKD). This study includes three clinic in person visits and weekly telephone visits for 12 weeks. 1. Recruit 28 patients with CKD stages 3b-4 and follow up for 12 weeks 2. Determine the effect of interventions on the primary outcome variable serum klotho measured by immunoprecipitation-immunoblot
Call 214-648-5005
studyfinder@utsouthwestern.edu, ZHENGNAN.WANG@UTSouthwestern.edu
Robert Toto
All
18 Years to 80 Years old
Phase 1
NCT05033054
STU-2021-0492
Inclusion Criteria:
• 18-80 years of age
• All races and ethnicities
• All genders
• Type 2 diabetes mellitus
• History of hypertension defined as > 130 or > 80 mmHg or normotensive on pharmacologic therapy
• Estimated glomerular filtration rate (GFR) (CKD Epi equation) of 15-44 ml/min/1.73 m2 (Stages 3b-4 CKD)
• Urinary albumin creatinine ratio of > 200 mg/g <5000mg/g
• Ability of study participant or legally authorized representative to provide informed written consent
• Able to maintain stable dose of any vitamin D and any calcium supplements for 180 days post randomization.
Exclusion Criteria:
• Autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
• Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
• History of organ transplantation
• Receiving therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
• Type 1 diabetes (T1D)
• Active use of SGLT2 inhibitor
• History of persistent hypercalcemia (serum total Calcium > 10.5 mg/dl)
• Body mass index > 45 kg/m2
• Active on kidney transplant list
• Inability to provide informed consent
• Any condition outside the renal and cardiovascular disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator´s clinical judgement
• Active malignancy requiring treatment at the time of screening (with the exception of successfully treated basal cell or treated squamous cell carcinoma).
• Hepatic impairment (aspartate transaminase [AST] or alanine transaminase [ALT] >3x the upper limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment)
• Women of child-bearing potential (ie, those who are not chemically or surgically sterilized or who are not post-menopausal) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator or women who have a positive pregnancy test at enrolment or randomization or women who are breast-feeding
• Participation in another clinical study with an investigational product (IP) during the last month prior to Enrolment
• Inability of the patient, in the opinion of the investigator, to understand and/or comply with procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study. Patients who cannot complete the patient reported outcome (PRO) assessments can still participate in the study
Drug: SGLT2 inhibitor
Diabetes, Kidney Disease, Chronic
UT Southwestern; Parkland Health & Hospital System
A Study of Intravesical Enfortumab Vedotin For Treatment of Patients With Non-muscle Invasive Bladder Cancer (NMIBC)
This study will test a drug called enfortumab vedotin in participants with a type of bladder cancer called non-muscle invasive bladder cancer (NMIBC). This study will also evaluate what the side effects are and if the drug works to treat NMIBC. A side effect is anything a drug does to your body besides treating your disease. In this study enfortumab vedotin will be put into the bladder using a catheter. A catheter is a thin tube that can be put into your bladder.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
ALL
18 Years and over
PHASE1
NCT05014139
STU-2021-0778
Inclusion Criteria:
* Histologically confirmed, non-muscle invasive urothelial carcinoma with carcinoma in situ (CIS) (with or without papillary disease)
* Predominant histologic component (\>50 percent) must be urothelial (transitional cell) carcinoma
* Participants must have high-risk Bacillus Calmette-Guerin (BCG) - unresponsive disease, defined as (where adequate BCG therapy is defined as one of the following: 5 of 6 doses of an initial induction course + at least 2 of 3 doses maintenance therapy or 5 of 6 doses of an initial induction course + at least 2 of 6 doses of a second induction course):
* Persistent or recurrent CIS alone or with recurrent Ta/T1 (noninvasive papillary disease/tumor invades the subepithelial connective tissue) disease within 12 months of completion of adequate BCG therapy.
* Recurrent high-grade Ta/T1 disease within 6 months of completion of adequate BCG therapy, or
* T1 high-grade disease at the first evaluation following an induction BCG course (at least 5 or 6 doses)
* Participant must be ineligible for or refusing a radical cystectomy
* All visible papillary Ta/T1 tumors must be completely resected within 60 days prior to enrollment.
* Eastern Cooperative Oncology Group Performance Status score of 0, 1, or 2.
Exclusion Criteria:
* Current or prior history of muscle-invasive urothelial carcinoma or metastatic disease.
* Nodal or metastatic disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) within 3 months prior to study treatment
* Concomitant upper tract urothelial carcinoma as noted on CT or MRI urogram performed within 3 months prior to study treatment
* Prior or concomitant urothelial carcinoma of the prostatic urethra within 6 months prior to study treatment
* Participants with tumor-related hydronephrosis
* Participant has received other systemic anticancer therapy including chemotherapy, biologic therapy, immunotherapy, targeted therapy, endocrine therapy, and/or investigational agent within 4 weeks or intravesical therapy within 6 weeks of first dose of study treatment
* Participant has had any prior radiation to the bladder for urothelial cancer DRUG: Enfortumab vedotin
Urinary Bladder Neoplasms, Carcinoma In Situ, Urinary Bladder, Non-muscle Invasive Bladder Cancer, Carcinoma Transitional Cell, NMIBC
Bladder Cancer, Urothelial Cancer, Enfortumab vedotin, PADCEV, Pharmacokinetics
UT Southwestern
[18F]PT2385 PET/CT in Patients with Renal Cell Carcinoma
This is an exploratory study to assess \[18F\]PT2385 Positron Emission Tomography/Computed Tomography (PET/CT) in patients with renal cell carcinoma (RCC). This is an open-label, nontherapeutic trial. The main objective is to correlate hypoxia-inducible factor-2alpha (HIF2α) levels as determined by an investigational \[18F\]PT2385 PET/CT scan with the levels on subsequently obtained tissue by HIF2α immunohistochemistry (IHC). There will be three cohorts. The first pre-surgical cohort will have \[18F\]PT2385 PET/CT prior to nephrectomy. The uptake and retention on Positron Emission Tomography (PET), quantified as standardized uptake value (SUV) max and mean, abbreviated SUV henceforth will be correlated with HIF2α levels by IHC on the primary tumor. The second cohort will comprise patients with metastatic clear cell renal carcinoma (ccRCC). SUV will be correlated with HIF2α levels measured by IHC on a biopsy sample from a metastasis. Both low- and high-avidity sites will be biopsied and tracer uptake correlated with HIF2α IHC. A third cohort will include patients with Von Hippel-Lindau (VHL) syndrome and any of the following disease manifestations - RCC, central nervous system (CNS) hemangioblastoma, and/or pancreatic neuroendocrine tumor(s). Investigational imaging will evaluate HIF2α expression within a tumor type and across different tumor types. A biopsy is encouraged but not mandatory for this cohort.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
James Brugarolas
ALL
18 Years and over
PHASE1
NCT04989959
STU-2021-0592
Inclusion Criteria:
* Ability to understand and the willingness to sign a written informed consent that includes study interventions (PET/CT and, if cohort 2, mandatory biopsy).
* Ability to lie still for a 30- to 60-minute PET/CT scan.
* One of the following:
• Cohort 1. Patients with suspected RCC planned for surgery.
• Cohort 2. Patients with metastatic ccRCC or VHL syndrome and RCC. Biopsy is required (planned resection for treatment reasons of a metastatic site is acceptable in lieu of the biopsy).
• Cohort 3. Patients with VHL syndrome with RCC, CNS hemangioblastoma, and/or pancreatic neuroendocrine tumor(s) planning to start belzutifan. * Patients with liver dysfunction will be considered "patients of special interest," and enrollment is allowed with or without criteria outlined for Cohorts 1-3. Liver dysfunction is defined clinically and is typically supported by abnormalities in imaging or laboratory studies (alanine / aspartate amino-transferase, bilirubin, alkaline phosphatase, or international normalized range (INR) for prothrombin time). * Women of child-bearing potential must agree to undergo and have documented a negative pregnancy test on the day of \[18F\]PT2385 administration. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
* Uncontrolled severe and irreversible intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
* Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
* Claustrophobia or other contraindications to PET/CT.
* Subjects must not weigh more than the maximum weight limit for the table for the PET/CT scanner where the study is being performed (\>200 kilograms or 440 pounds).
* For cohort 2 patients, lack of suitable sites for mandatory biopsy. For example, patients with metastatic disease restricted to the lungs that would require percutaneous biopsies with associated risk of bleeding and pneumothorax will be excluded. DRUG: [18F]PT2385, PROCEDURE: Positron Emission Tomography/Computed Tomography, PROCEDURE: Biopsy
Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma, Kidney
UT Southwestern; Parkland Health & Hospital System
Testing Combination Erdafitinib and Enfortumab Vedotin in Metastatic Bladder Cancer After Treatment With Chemotherapy and Immunotherapy
This phase Ib trial evaluates the best dose, potential benefits, and/or side effects of erdafitinib in combination with enfortumab vedotin in treating patients with bladder cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and possesses genetic alterations in FGFR2/3 genes. Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals cancer cells to multiply. This may help keep cancer cells from growing and may kill them. Enfortumab vedotin is a monoclonal antibody, enfortumab, linked to an anticancer drug called vedotin. It works by helping the immune system to slow or stop the growth of cancer cells. Enfortumab attaches to a protein called nectin-4 on cancer cells in a targeted way and delivers vedotin to kill them. It is a type of antibody-drug conjugate. Giving erdafitinib in combination with enfortumab vedotin may shrink or stabilize metastatic bladder cancer with alterations in FGFR 2/3 genes.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Waddah Arafat
ALL
18 Years and over
PHASE1
NCT04963153
STU-2023-0272
Inclusion Criteria:
* Patients must have histologically or cytologically documented locally advanced (T4b, any N; or any T, N 2-3) or metastatic (M1, Stage IV; or metastatic recurrence after locoregional treatment) urothelial carcinoma (including renal pelvis, ureters, urinary bladder, urethra). Patients with mixed histologies are required to have a dominant transitional cell pattern
* Patients who had disease progression during or following treatment with at least one platinum-containing regimen (e.g., gemcitabine and cisplatin \[GC\], methotrexate, vinblastine, doxorubicin and cisplatin \[MVAC\], carboplatin and gemcitabine \[Carbo-Gem\]) and an immune checkpoint inhibitor (PD-1/ PD-L1 inhibitor including but not limited to: atezolizumab, pembrolizumab, durvalumab, avelumab, and nivolumab)
* Received a first-line platinum-containing regimen in the metastatic setting or for inoperable locally advanced disease
* Or received neo/adjuvant platinum-containing therapy for localized muscle-invasive UC, with recurrence/progression =\< 12 months following completion of therapy
* Patients who received immune checkpoint inhibitor therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 12 months of therapy completion are eligible. This criterion does not apply if the checkpoint inhibitor is contraindicated
* Patients with metastatic urothelial carcinoma who are cisplatin-ineligible and progressed on upfront immune checkpoint inhibitor; or ineligible/refused immune checkpoint inhibitor therapy will be eligible for this trial
* Patient who received prior antibody drug conjugate such as sacituzumab govitecan are allowed
* Patients must have measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Previously irradiated lesions cannot be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy and no other lesions are available for selection as target lesions
* Patients must have FGFR2/3 activating alterations identified by tumor tissue or plasma ctDNA profiling using a Clinical Laboratory Improvement Act (CLIA) certified College of American Pathologists (CAP) accredited platform
* Age \>= 18 years, for ability to comply with protocol
* Because no dosing or adverse event data are currently available on the use of erdafitinib in combination with enfortumab vedotin in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Absolute neutrophil count \>= 1,500/mcL (within 14 days prior to beginning trial treatment)
* Platelets \>= 100,000/mcL (within 14 days prior to beginning trial treatment)
* Hemoglobin \>= 9 g/dL (within 14 days prior to beginning trial treatment)
* Measured or calculated creatine clearance (CrCl) \>= 30 ml/min (glomerular filtration rate \[GFR\] can also be used in place of creatinine CrCl) (within 14 days prior to beginning trial treatment)
* Total bilirubin =\< 1.5 x ULN (institutional upper limit of normal) OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 x ULN (within 14 days prior to beginning trial treatment)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x institutional ULN (=\< 5 x ULN for subjects with liver metastasis) (within 14 days prior to beginning trial treatment)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression (CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis)
* Patients with a history of prostate cancer (T2NXMX or lower with Gleason score =\< 7) treated with definitive intent (surgically or with radiation therapy) at least 1 year prior to study entry are eligible, provided that the subject is considered prostate cancer-free and the following criteria are met:
* Patients who have undergone radical prostatectomy must have undetectable prostate specific antigen (PSA) for \> 1 year and at screening
* Patients who have had radiation must have a PSA doubling time \> 1 year (based on at least 3 values determined \>1 month apart) and a total PSA value that does not meet Phoenix criteria for biochemical recurrence (i.e., \< 2.0 ng/mL above nadir)
* Patients with untreated low-risk prostate cancer (Gleason score =\< 6) on active surveillance with PSA doubling time \>1 year (based on at least 3 values determined \> 1 month apart) are also eligible
* Patients who have undergone an ophthalmologic examination and have no active eye disease which would be likely to increase the risk of eye toxicity
* The effects of erdafitinib and enfortumab vedotin on the developing human fetus are unknown. For this reason and because FGFR inhibitors and humanized antibody-drug conjugate (ADC) agents are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 3 months after completion of erdafitinib and enfortumab vedotin administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 5 months after completion of erdafitinib and enfortumab vedotin administration
* Ability to understand and willingness to sign a written informed consent document
Exclusion Criteria:
* Patients who have had chemotherapy, targeted therapies, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
* Patients who have not recovered from adverse events due to prior anti-cancer therapy (including ongoing sensory or motor neuropathy of grade 2 or higher) (i.e., have residual toxicities \> grade 1 or returned to baseline) with the exception of alopecia. Subjects with =\< grade 2 immunotherapy- related hypothyroidism or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of hormone replacement therapy (if indicated). Subjects with ongoing \>= grade 3 immunotherapy-related hypothyroidism or panhypopituitarism are excluded. Subjects with ongoing immunotherapy related colitis, uveitis, myocarditis, or pneumonitis or subjects with other immunotherapy related adverse events (AEs) requiring high doses of steroids (\> 20 mg/day of prednisone or equivalent) are excluded
* Patients who have previously received enfortumab vedotin or other MMAE-based ADCs
* Patients who have had prior treatment with an FGFR inhibitor
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to erdafitinib and enfortumab vedotin
* Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
* Patients with a history of any corneal or retinal abnormality likely to increase the risk of eye toxicity
* Patients with uncontrolled intercurrent illness and currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of starting treatment. Routine antimicrobial prophylaxis is permitted
* Patients with psychiatric illness/social situations that would limit compliance with study requirements
* Subjects who have received radiotherapy within 2 weeks prior to start of treatment. Subject must have recovered adequately from the toxicity from the intervention prior to starting study treatment
* Patients with uncontrolled diabetes. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) \>= 8% or HbA1c 7% to \< 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained
* Subjects who have received major surgery within 4 weeks prior to start of treatment. Subject must have recovered adequately from complications from the intervention prior to starting study treatment
* Subjects who have received a prior allogeneic stem cell or solid organ transplant
* Has persistent phosphate level \> ULN during screening (within 14 days of treatment and prior to cycle 1 day 1) and despite medical management
* Has a history of or current uncontrolled cardiovascular disease including:
* Unstable angina, myocardial infarction, or known congestive heart failure class II-IV within the preceding 12 months; cerebrovascular accident or transient ischemic attack within the preceding 3 months
* Any of the following: sustained ventricular tachycardia, ventricular fibrillation, Torsades de Pointes, cardiac arrest, Mobitz II second degree heart block or third degree heart block; known presence of dilated, hypertrophic, or restrictive cardiomyopathy
* QTc prolongation as confirmed by triplicate assessment at screening (Fridericia;QTc \> 480 milliseconds)
* Subjects with a history of another invasive malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Subjects with nonmelanoma skin cancer or carcinoma in situ of any type (if complete resection was performed) are allowed PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography, DRUG: Enfortumab Vedotin, DRUG: Erdafitinib, PROCEDURE: Multigated Acquisition Scan
Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Stage IV Bladder Cancer AJCC v8, Locally Advanced Bladder Urothelial Carcinoma, Locally Advanced Ureter Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Gall Bladder, Other Urinary, Urinary Bladder, Stage IV Urethral Cancer AJCC v8, Locally Advanced Renal Pelvis Urothelial Carcinoma, Locally Advanced Urethral Urothelial Carcinoma, Stage IV Renal Pelvis Cancer AJCC v8, Stage IV Ureter Cancer AJCC v8, Recurrent Bladder Urothelial Carcinoma, Recurrent Renal Pelvis Urothelial Carcinoma, Recurrent Ureter Urothelial Carcinoma, Recurrent Urethral Urothelial Carcinoma, Recurrent Urothelial Carcinoma, Stage IIIB Bladder Cancer AJCC v8
UT Southwestern
Olanzapine Versus Megestrol Acetate for the Treatment of Loss of Appetite Among Advanced Cancer Patients
This phase III trial compares the effects of olanzapine versus megestrol acetate in treating loss of appetite in patients with cancer that has spread to other places in the body (advanced). Olanzapine may stimulate and increase appetite. This study aims to find out if olanzapine is better than the usual approach (megestrol acetate) for stimulating appetite and preventing weight loss.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
ALL
18 Years and over
PHASE3
NCT04939090
STU-2021-1170
Inclusion Criteria:
* Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives or double barrier method (diaphragm plus condom)
* Diagnosis of advanced cancer
* Patient-reported 2-month weight loss of at least 5 pounds (2.3 kilograms) and/or physician-estimated caloric intake of less than 20 calories/kilogram of body weight per day
* The patient must perceive loss of appetite and/or weight as a problem; and have an appetite score of 4 or worse on the "Please rate your appetite...." question that requires a patient response on a 0-10 numeric rating scale
* Not receiving ongoing tube feedings or parenteral nutrition at the time of registration
* Not currently using systemic adrenal steroids (with the exception of short-term dexamethasone within 3 days of chemotherapy for control of chemotherapy side effects)
* No use of androgens, progesterone analogs, or other appetite stimulants within the past month
* Patient should not have poorly controlled hypertension or congestive heart failure at registration
* Patient should not have an obstruction of the alimentary canal, malabsorption, or intractable vomiting (defined as vomiting more than 3 times per day over the preceding week)
* Not currently using olanzapine for another medical condition or had previously used olanzapine for chronic nausea or for any pre-existing psychotic disorder
* Patient should not have had a previous blood clot at any time in the past
* No history of poorly controlled diabetes
* No symptomatic leptomeningeal disease or known brain metastases as these patients may have difficulty taking oral medications
* No history of hypersensitivity to olanzapine or megestrol acetate
* No COVID-19 infection in the past that, in the opinion of the treating physician, had left patients with compromised taste, which has not resolved at the time of registration
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative urine or serum pregnancy test done =\< 14 days prior to registration is required
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Estimated life expectancy of 3 months or longer
* Serum creatinine =\< 2.0 mg/dL
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x upper limit of normal (ULN)
* Fasting glucose \< 140 mg/dL
* Granulocytes \> 1000/hpf
* No treatment with another antipsychotic agent, such as risperidone, quetiapine, clozapine, butyrophenone within 30 days of enrollment
* In order to complete the mandatory patient-completed measures, participants must be able to speak and/or read English or Spanish. Sites seeking to enroll Spanish-speaking patients should have access to Spanish speaking staff on site or through the use of a translation service to be able to conduct the informed consent discussion in Spanish, and to conduct the weekly phone calls
Exclusion Criteria:
* Psychiatric illness which would prevent the patient from giving informed consent
* Medical condition such as uncontrolled infection (including human immunodeficiency virus \[HIV\]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
* Patients who cannot swallow oral formulations of the agents
* Patients with impaired decision-making capacity (such as with a diagnosis of dementia or memory loss) are not eligible for this study
* No presence of a hormone-sensitive tumor, such as breast, endometrial, or prostate cancer (this exclusion criterion is intended to circumvent any confounding antineoplastic effects of megestrol acetate) DRUG: Olanzapine, DRUG: Megestrol Acetate, OTHER: Questionnaire Administration
Lymphoma, Sarcoma, Anorexia, Multiple Myeloma, Mycosis Fungoides, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, Carcinoid Tumor, Cardiovascular, Cervix, Colon, Corpus Uteri, Ear, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Nose, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Leukemia, Other, Hodgkins Lymphoma, Heart, Kaposis sarcoma, Leukemia, Not Otherwise Specified, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Non-Hodgkins Lymphoma, Other Hematopoietic, Psychiatric Disorders, Small Intestine, Soft Tissue, Unknown Sites, Ill - Defined Sites
UT Southwestern
Gemcitabine Versus Water Irrigation in Upper Tract Urothelial Carcinoma
There is a high rate of intravesical (bladder) recurrence following extirpative surgery for upper tract urothelial carcinoma. There is no single established standard of care for prevention of intravesical recurrence; however, one protocol in common use involves the use of intravesical gemcitabine instilled into the bladder during surgery and prior to entry into the bladder. There are barriers to the use of gemcitabine, especially at lower volume centers. Some evidence suggests that intravesical irrigation with sterile water has equivalent efficacy to intravesical chemotherapy in prevention of recurrent bladder cancer following transurethral resection of bladder tumors (TURBT). This study is intended to compare recurrence rates using intravesical gemcitabine (as a pseudo-standard of care) and continuous bladder irrigation with sterile water.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
All
18 Years to 90 Years old
Phase 3
NCT04865939
STU-2021-0402
Inclusion Criteria:
• Biopsy proven UTUC with plan for excisional surgery (distal ureterectomy or nephroureterectomy) with curative intent
• Age 18 - 90 years
• Life expectancy > 1 year
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Female participants who become pregnant or who suspect that they are pregnant should notify the treating investigator immediately.
• Ability to understand and the willingness to sign a written informed consent.
Exclusion Criteria:
• Concurrent or prior diagnosis of bladder cancer with a disease-free interval of less than three years.
• Synchronous bilateral upper tract urothelial carcinoma (prior history of contralateral UTUC is permissible with a disease-free interval of more than three years).
• Plan for radical cystectomy.
• 3.2.4 Suspicion for small bladder capacity (< 100 mL) based on treating urologist's clinical judgment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or other agents used in study.
Procedure: sterile water irrigation, Drug: Gemcitabine
Urinary Bladder, Urothelial Cancer of Renal Pelvis, Urothelial Carcinoma Ureter
UT Southwestern
Use of DNA Testing to Help Transition Kidney Transplant Recipients to Belatacept-only Immunosuppression
The purpose of the study is to identify kidney transplant patients that can be transitioned from multi-drug immunosuppression therapy to Belatacept monotherapy, using cell free DNA and gene expression as markers of immune quiescence. The primary objective will be to determine if donor derived-cell free DNA (AlloSure) can be utilized to facilitate Belatacept monotherapy, and to determine if Belatacept is safe and effective as immunosuppression in kidney transplant recipients. The secondary objective is to determine the utility of AlloMap as a predictor of immune quiescence and tolerance of immunosuppressive de-escalation to Belatacept monotherapy, and to evaluate the performance of iBox in predicting adverse outcomes in patients transitioned to Belatacept monotherapy
Call 214-648-5005
studyfinder@utsouthwestern.edu, Morgan.Marsh@UTSouthwestern.edu
David Wojciechowski
All
18 Years and over
Phase 4
NCT04786067
STU-2020-1339
Inclusion Criteria:
• Adult (>18 years) recipients of a kidney-only transplant, including re-transplants
• Non-HLA identical Living or Deceased Donor Grafts
• Able to provide informed consent
• Absence of donor specific antigens
• Stable renal function (eGFR>40mL/min for 3 months prior to enrollment)
• Patients treated with Belatacept as part of de novo immunosuppression or converted to Belatacept with stable kidney function for 3 months (as stated above)
• Patients who underwent kidney transplantation at least 9 months prior to study entry
Exclusion Criteria:
• Prior or concurrent non-kidney organ transplants
• Presence of BK nephropathy in current graft
• Recipient on any other investigational drug in the 12 weeks prior to inclusion
• Patient with history of recent (<3mo), recurrent, or severe (Banff Grade 2 or greater or unable to be treated with steroids) acute rejection episodes
• Female participant who is pregnant, lactating or planning pregnancy during the course of the trial
• Significant hepatic impairment
• Bilateral kidney transplantation
• Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial
Drug: Belatacept
Kidney, Kidney Transplant Immunosuppression
UT Southwestern
A Phase 1 Study With ABBV-CLS-484 in Subjects With Locally Advanced or Metastatic Tumors
The study will assess the safety, PK, PD, and preliminary efficacy of ABBV-CLS-484 as monotherapy and in combination with a PD-1 targeting agent or with a or a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). The trial aims to establish a safe, tolerable, and efficacious dose of ABBV-CLS-484 as monotherapy and in combination. The study will be conducted in three parts. Part 1 Monotherapy Dose Escalation, Part 2 Combination Dose Escalation and Part 3 Dose Expansion (Monotherapy and Combination therapy). Part 1, ABBV-CLS-484 will be administered alone in escalating dose levels to eligible subjects who have advanced solid tumors. Part 2, ABBV-CLS-484 will be administered at escalating dose levels in combination with a PD-1 targeting agent or with a VEGFR TKI to eligible subjects who have advanced solid tumors. Part 3, ABBV-CLS-484 will be administered alone as a monotherapy at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC). ABBV-CLS-484 will also be administered at the determined recommended dose in combination with a PD-1 targeting or with a VEGFR TKI agent in subjects with locally advanced or metastatic, HNSCC, NSCLC, MSI-H tumors refractory to PD-1/PD-L1, and advanced ccRCC.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years and over
PHASE1
NCT04777994
STU-2023-0762
Inclusion Criteria:
* Must weigh at least 35 kilograms (kg).
* An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Life expectancy of ≥ 12 weeks.
* Laboratory values meeting protocol criteria.
* QT interval corrected for heart rate \< 470 msec (using Fridericia's correction), and no clinically significant electrocardiographic findings.
* Measurable disease defined by RECIST 1.1 criteria.
For Monotherapy and Combination Dose Escalation:
• Subjects with histologically or cytologically proven metastatic or locally advanced tumors, for which no effective standard therapy exists, or where standard therapy has failed. Subjects must have received at least 1 prior systemic anticancer therapy for the indication being considered.
For Monotherapy Dose Expansion only:
* Subjects must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with a best response by RECIST v1.1 of CR/PR/stable (any duration) or stable disease (for greater than 6 months); AND
* Must have been previously treated with 1 or more prior lines of therapy in the locally advanced or metastatic setting with the following tumor types:
* Relapsed/refractory HNSCC
* Relapsed/refractory NSCLC
* Advanced ccRCC
For PD-1 Targeting Agent Combination Dose Expansion only:
* For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy with response by RECIST v1.1 of CR/PR (any duration) or stable disease (for greater than 6 months):
* Relapsed HNSCC
* Relapsed NSCLC
* Relapsed Advanced ccRCC
* For the following tumor types, subject must have received at least 1 prior line containing PD-1/PD-L1 targeted therapy and have had disease progression with PD-1/PD-L1 targeted therapy:
* Locally Advanced or metastatic MSI-H tumors
For VEGFR TKI Combination Dose Expansion only:
* Relapsed advance ccRCC with no more than 1 prior VEGFR TKI
* Subjects no recent history of hemorrhage, including hemoptysis, hematemesis, or melena
* Subjects with poorly controlled hypertension are excluded
Exclusion Criteria:
* Untreated brain or meningeal metastases (i.e., subjects with history of metastases are eligible provided they do not require ongoing steroid treatment and have shown clinical and radiographic stability for at least 28 days after definitive therapy)
* Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except alopecia.
* Unresolved Grade 2 or higher peripheral neuropathy.
* History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
* Recent history (within 6 months) of congestive heart failure (defined as New York Heart Association, Class 2 or higher), ischemic cardiovascular event, pericarditis, or clinically significant pericardial effusion or arrythmia.
* Recent history (within 6 months) of Childs-Pugh B or C classification of liver disease.
* History of clinically significant medical and/or psychiatric conditions or any other reason that, in the opinion of the investigator, would interfere with the subject's participation in this study or would make the subject an unsuitable candidate to receive study drug.
* History of uncontrolled, clinically significant endocrinopathy.
* Known gastrointestinal disorders making absorption of oral medications problematic; subject must be able to swallow capsules.
* If treated with a PD-1/aPD-L1 targeting or other immune-oncology agents in the past, excluded if had prior pneumonitis, prior Grade 3 or higher immune mediated toxicity, hypersensitivity to administered drug or drug related toxicity requiring discontinuation.
* Active autoimmune disease requiring systemic treatment in past 2-years (exceptions for endocrinopathies, vitiligo or atopic conditions).
* History of solid organ transplant or allogeneic stem cell transplant.
* History of other malignancy, with the following exceptions:
* No known active disease present within ≥ 3 years before first dose of study treatment and felt to be at low recurrence by investigator.
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
* Adequately treated carcinoma in situ without evidence of disease.
* History of interstitial lung disease or pneumonitis.
* Major surgery ≤ 28 days prior to first dose of study drug
* Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local testing practices. DRUG: ABBV-CLS-484, DRUG: Programmed Cell Death-1 (PD-1) Inhibitor, DRUG: Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
Cervix, Colon, Kidney, Lung/Thoracic, Ovary, Advanced Solid Tumor Cancer
Cancer, Tumor, anti-PD-1, ABBV-CLS-484, clear cell renal cell carcinoma (ccRCC), head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), relapsed or refractory (R/R), Microsatellite instability - high tumors (MSI-H), Vascular Endothelial Growth Factor Receptor (VEGFR) Tyrosine Kinase Inhibitor (TKI)
UT Southwestern
Diuretic Tuner Clinical Decision Support
This purpose of this study is to determine the effectiveness of a mobile phone application in helping to control body swelling in patients with kidney problems. The application will help in the day to day adjustments in diuretic medication dosing. Participants in this study will have an application loaded on to their mobile phone by the study team and be taught how to use it over a 2 hour visit. Participants will need to check their blood pressure and weight daily and enter this information into the mobile phone application every day. Participants will need to follow daily instructions in their medication dosing provided by the application. There will be periodic blood testing. This will happen at 2 weeks, 90 days, and up to 4 other times if necessary. At the end of the study there is a 2 hour study visit during which participants will answer a survey. The total length of the study is 90 days.
Call 214-648-5005
studyfinder@utsouthwestern.edu, KSAMBANDAM@UTSouthwestern.edu
Kamalanathan Sambandam
All
18 Years and over
N/A
NCT04759274
STU-2020-1124
Inclusion Criteria:
• The presence of nephrotic range proteinuria (> 3 g/d proteinuria by 24hr urine protein, 24hr urine albumin, spot urine protein/creatinine ratio, or spot urine albumin/creatinine ratio) or stage 4 or 5 chronic kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73 m2 by Modification of Diet in Renal Disease equation) PLUS
• Clinical signs of hypervolemia present (lower extremity edema, ascites, or pleural effusions) with an estimated dry weight (defined as edema-free weight without orthostatic hypotension) 5 lbs less than enrollment body weight
Exclusion Criteria:
• Weight < 100 lbs or > 300 lbs.
• Autonomic insufficiency resulting in orthostatic hypotension at screening
• Hypokalemia at enrollment (defined as serum potassium < 3.5 mmol/L)
• Moderate to severe hyponatremia at enrollment (defined as serum sodium < 130 mmol/L)
• Serum creatinine > 6 mg/dL or > 1.5 times baseline
• Patients who are unable or unwilling to measure their home blood pressures and weights
• Patients without a working phone number and smart phone device
• Expectation that the patient will require dialysis initiation within < 3 months
• Expected lifespan of < 6 months
• The presence of a medical condition that would interfere with effectively using the Diuretic Tuner (dementia, illiteracy, or blindness)
• Pregnant patients
• Prisoners
Device: Diuretic Tuner
Nephrotic Syndrome, Chronic Kidney Diseases, Kidney, Edema, Hypervolemia
UT Southwestern; Parkland Health & Hospital System
Ferric Citrate and Chronic Kidney Disease in Children (FIT4KID)
We will conduct a 12-month, double-blind, randomized, placebo-controlled trial to assess the effects of therapy with ferric citrate (FC) on changes in intact FGF23 levels (iFGF23, primary endpoint) in 160 pediatric patients (80 in each of the two arms) aged 6-18 years of either sex with chronic kidney disease (CKD) stages 3-4 and age-appropriate normal serum phosphate levels. Participants will be randomized to one of the two groups: 1) FC or 2) FC placebo. Participants will be recruited from 12 core clinical sites.
Call 214-648-5005
studyfinder@utsouthwestern.edu, melaku.lemma@childrens.com
Raymond Quigley
All
6 Years to 18 Years old
Phase 2
NCT04741646
STU-2020-1055
Inclusion Criteria:
• Ages 6 to 18 years (inclusive);
• Estimated Glomerular Filtration Rate (GFR) of 15-59 ml/min per 1.73 m2 by modified Chronic Kidney disease in Children (CKiD) formula;56
• Serum phosphate within age appropriate normal levels;
• Serum ferritin <500 ng/ml and TSAT <50%;
• For those patients treated with growth hormone, calcitriol, nutritional vitamin D, iron, and/or erythropoiesis-stimulating agents (ESAs) such treatments must have stable dosing for at least 2 weeks prior to screening;
• Able to swallow tablets;
• Able to eat at least two meals a day;
• In the opinion of the investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations.
Exclusion Criteria:
• Patients currently treated with phosphate binders.
• History of allergy to all ingredients (including non-medical ingredients) in both products (i.e. investigational product and placebo)
• Current intestinal malabsorption, documented in the medical record; significant GI disorders including GI bleeding or active inflammatory bowel disease, inflammatory bowel syndrome, and/or Crohn's Disease
• Anticipated initiation of dialysis or kidney transplantation within 6 months
• Current or planned future systemic immunosuppressive therapy
• Prior solid organ transplantation
• Receipt of bone marrow transplant within two years of screening
• Current pregnancy, lactation or female subjects who have reached menarche, unless using highly-effective contraception as outlined in section 7.1.1 of Protocol
• Patients participating in other interventional study (observational study participation permitted)
• Poor adherence to medical treatments in the opinion of the investigator
• Hemochromatosis or laboratory tests indicating possible hemochromatosis or other iron overload (primary or secondary) syndrome
• Cystinosis
• Fanconi syndrome
Drug: Ferric Citrate, Drug: Placebo
Chronic Kidney Diseases, Kidney
Pediatric, CKD, Phosphate Binder
Children’s Health
LEGEND Study: EG-70 in NMIBC Patients BCG-Unresponsive and High-Risk NMIBC Incompletely Treated With BCG or BCG-Naïve
This study will evaluate the safety and efficacy of intravesical administration of EG-70 in the bladder and its effect on bladder tumors in patients with NMIBC. This study study consists of two phases; a Phase 1 dose-escalation to establish safety and recommended the phase 2 dose, followed by a Phase 2 study to establish how effective the treatment is. The Study will include patients with NMIBC with Cis for whom BCG therapy is unresponsive and patients with NMIBC with Cis who are BCG-naïve or inadequately treated.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
ALL
18 Years and over
PHASE1
NCT04752722
STU-2021-0254
Inclusion Criteria:
BCG-unresponsive Patients:
• BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without coexisting papillary Ta/T1 tumors who are ineligible for or have elected not to undergo cystectomy, and have experienced 1) persistent disease within 12 months of treatment or 2) a recurrence within 6 months of completion of adequate BCG therapy, where: adequate BCG regimen consists of at least 2 courses of BCG where the first course (induction) must have included at least 5 or 6 doses and the second course may have included a re-induction (at least 2 treatments) or maintenance (at least 2 doses), and Cis must be documented or indicated by pathology BCG-Naïve or BCG-incompletely treated Patients (Phase 2 Only):
• NMIBC with current Cis of the bladder, with or without coexisting papillary Ta/T1 NMIBC tumor(s), who are ineligible for or have elected not to undergo cystectomy, where: either: a) incomplete BCG (at least 1 dose) treatment or b) no treatment with BCG but who have previously been treated with at least 1 dose of intravesical chemotherapy following transurethral resection of bladder tumor (TURBT), and Cis must be documented or indicated by pathology All Patients:
• Patients who have previously been treated with an investigational or approved checkpoint inhibitor (e.g., pembrolizumab) and failed treatment are eligible for inclusion 30 days post-treatment (Phase 1) or 3 months post-treatment (Phase 2).
• Male or non-pregnant, non-lactating female, 18 years or older.
• Women of childbearing potential must have a negative pregnancy test at Screening.
• Female patients of childbearing potential must be willing to consent to using highly effective birth control methods while on treatment and for 3 months (or longer in accordance with local regulatory requirements) after their participation in the study ends; Male patients are required to utilize a condom for the duration of the study treatment through 3 months post-dose.
• In Phase 2, for patients with T1 lesions, Screening biopsy must be considered adequate (contain the muscularis layer).
• Performance Status: Eastern Cooperative Oncology Group 0, 1, and 2.
• Hematologic inclusion:
• Absolute neutrophil count \>1,500/mm3.
• Hemoglobin \>9.0 g/dL.
• Platelet count \>100,000/mm3.
• Hepatic inclusion:
• Total bilirubin must be ≤1.5 x the upper limit of normal (ULN).
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase ≤2.5 x ULN.
• Adequate renal function with creatinine clearance \>30 mL/min
• Prothrombin time and partial thromboplastin time ≤1.25 x ULN or within the therapeutic range if on anticoagulation therapy.
• Must have satisfactory bladder function with ability to retain study drug for a minimum of 60 minutes.
• Patient or legally authorized representative must be willing and able to comply with all protocol requirements.
• Must be willing and able to give informed consent.
Exclusion Criteria:
• Any malignancy (other than NMIBC) diagnosed within 1 year of study entry (except basal or squamous cell skin cancers or noninvasive cancer of the cervix) ), or any malignancy that has required therapy for active disease within the last 12 months.
• Concurrent treatment with any chemotherapeutic agent.
• History of partial cystectomy.
• Treatment with pembrolizumab within 30 days (Phase 1) or 3 months (Phase 2) prior to Screening.
• Treatment with last therapeutic agent (including intravesical chemotherapy post-TURBT) within 30 days of Screening.
• Evidence of persistent or ongoing renal failure.
• History of unresolved vesicoureteral reflux or an indwelling urinary stent.
• History of unresolved hydronephrosis due to ureteral obstruction.
• Participation in any other research protocol involving administration of an investigational agent within 30 Days prior to screening or any prior treatment of NMIBC with any investigational gene or immunotherapy agent.
• History of external beam radiation to the pelvis at any time or prostate brachytherapy within the last 12 months.
• History of interstitial lung disease and/or pneumonitis in patients who have previously received a PD-1 or PD-L1 inhibitor therapy.
• Evidence of metastatic disease.
• History of difficult catheterization that in the opinion of the Investigator will prevent administration of EG-70.
• Active interstitial cystitis on cystoscopy or biopsy.
• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Known human immunodeficiency virus, Hepatitis B, or Hepatitis C infection.
• Significant cardiovascular risk (e.g., coronary stenting within 8 weeks, myocardial infarction within 6 months).
• Hypersensitivity to any of the excipients of the study drug.
• Consideration by the Investigator that the patient is an unsuitable candidate for the study.
DRUG: EG-70 (phase 1), DRUG: EG-70 (phase 2)
Superficial Bladder Cancer, Urinary Bladder, Non-muscle Invasive Bladder Cancer With Carcinoma in Situ
Non-muscle invasive bladder cancer (NMIBC), Bacillus calmette- guerin (BCG) failure, BCG unresponsive, NMIBC, Bladder Cancer, LEGEND Study, EG-70, High-risk NMIBC, BCG-naïve, Incomplete BCG treatment, Carcinoma in situ (Cis)
UT Southwestern
Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy Before Surgery for Patients With High-Grade Upper Urinary Tract Cancer
This phase II/III trial compares the effect of adding durvalumab to chemotherapy versus chemotherapy alone before surgery in treating patients with upper urinary tract cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as methotrexate, vinblastine, doxorubicin, cisplatin, and gemcitabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Durvalumab in combination with chemotherapy before surgery may enhance the shrinking of the tumor compared to chemotherapy alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vitaly Margulis
ALL
18 Years and over
PHASE2
NCT04628767
STU-2021-0698
Inclusion Criteria:
* STEP 1 REGISTRATION AND RANDOMIZATION
* Patients must be \>= 18 years of age
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Patient must have a diagnosis of high grade upper tract urothelial carcinoma proven by biopsy within 12 weeks (84 days) prior to registration/randomization with one of the following:
* Upper urinary tract mass on cross-sectional imaging or
* Tumor directly visualized during upper urinary tract endoscopy before referral to medical oncology
* NOTE: Biopsy is standard of care (SOC) and required for enrollment to study. This is vital for best practice
* Leukocytes \>= 3,000/mcL (obtained =\< 14 days prior to registration/randomization)
* Platelets \>= 100,000/mcL (obtained =\< 14 days prior to registration/randomization)
* Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (or =\< 2.5 x ULN for patients with Gilbert's disease) (obtained =\< 14 days prior to registration/randomization)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (obtained =\< 14 days prior to registration/randomization)
* Hemoglobin (Hgb) \>= 9 g/dL (obtained =\< 14 days prior to registration/randomization)
* NOTE: Packed red blood transfusion is allowed to achieve this parameter as per treating investigator
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration/randomization are eligible for this trial
* NOTE: These patients must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks. They must have a CD4 count of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression. They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months
* NOTE: For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy. They must have an undetectable viral load and a CD4 count \>= 250 cells/mcL within 7 days of registration/randomization
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* NOTE: Testing for HIV, hepatitis B or hepatitis C is not required unless clinically indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patient must have a body weight of \> 30 kg
* Patient must have life expectancy of \>= 12 weeks
* Patient must have creatinine clearance \> 15 ml/min as by Crockroft-Gault formula or 24-hour creatinine clearance within 28 days prior to registration/randomization
* NOTE: Patients will be assigned to cisplatin-ineligible and cisplatin-eligible cohorts based on their creatinine clearance, Eastern Cooperative Oncology Group (ECOG) performance status, and grade (if any) of peripheral neuropathy and/or hearing loss in keeping with SOC cisplatin contraindications. Patients that are cisplatin-eligible will be randomized to either Arm A or Arm B
* Patients that meet any of the following criteria will be registered and assigned to the cisplatin-ineligible Arm C if they meet other eligibility criteria:
* Creatinine clearance \> 15 ml/min and =\< 50 ml/min or hearing loss grade \>= 3, or neuropathy \>= 2, or ECOG PS 2
* Patient must have an absolute neutrophil count (ANC) \>= 1,000/mcL obtained =\< 14 days prior to registration
* Patient must have ECOG performance status 0-2
* Patients that meet the following criteria will be randomized to the cisplatin-eligible Arm A or Arm B:
* Patient must have creatinine clearance of \> 50ml/min, PS ECOG 0-1, absence of hearing loss grade \>= 3, and/or neuropathy \>= 2
* Patient must have an absolute neutrophil count (ANC) \>= 1,500/mcL obtained =\< 14 days prior to randomization
* Patient must have left ventricular ejection fraction (LVEF) \>= 50% by (either multigated acquisition scan \[MUGA\] or 2-D echocardiogram) obtained within obtained within 28 days prior to randomization
Exclusion Criteria:
* Patients must not have any component of small cell/neuroendocrine carcinoma. Other variant histologic types are permitted provided the predominant (\>= 50%) subtype is urothelial carcinoma
* Patients must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any patient, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients of childbearing potential and sexually active patients must not expect to conceive or father children, either by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse from the time of registration, while on study treatment and for at least 6 months after the last dose of protocol treatment
* Patients must have no evidence of metastatic disease or clinically enlarged regional lymph nodes (\>= 1.5 cm short axis) on imaging required within 28 days prior to registration (Non-regional findings \>=1.5 cm short axis that in the opinion of the investigator are not concerning for involvement based on radiographic characteristics, chronicity, avidity on positron emission tomography (PET) or other imaging or other criteria can be eligible based on investigator discretion).
* NOTE: Patients with elevated alkaline phosphatase, calcium or suspicious bone pain/tenderness can also undergo baseline bone scans to evaluate for bone metastasis at the discretion of local provider.
* Patient must meet below criteria for prior/current malignancy history:
* Non-urothelial cancer malignancy history:
* Patient must not have another active (or within two years) second malignancy other than resected non-melanoma skin cancers, resected in situ breast, cervical or other in situ carcinoma, and either clinically insignificant per the investigator (e.g. =\< Gleason 3+4) on active surveillance (or watchful waiting) or previously treated prostate cancer with no rising prostate specific antigen (PSA) and no plan to treat
* NOTE: Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients in whom concomitant or prior bladder/urethra predominant (\>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only non-invasive cancer (\< cT1N0) are eligible regardless of time elapsed
* Urothelial cancer malignancy history:
* Patient may have a history of resectable urothelial cancer as long as patients meet one of the following:
* T0, Ta or Tis at any time
* T1-4a N0 and no evidence of disease (NED) for more than 2 years from the latest therapy \[e.g., radical surgery, transurethral resection of bladder tumor (TURBT), radiation, chemotherapy (neoadjuvant or adjuvant, or with radiation)\]. Prior immune checkpoint inhibitor is not allowed.
* Patient with history of \>= pT4b, N+, and/or M1 is not eligible.
* NOTE: Patients in whom concomitant or prior bladder/urethra predominant (\>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only Ta or carcinoma in situ (CIS) (\< cT1 N0) are eligible regardless of time elapsed
* Patient must not have any uncontrolled illness including, but not limited to, ongoing or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis \[TB\] testing in line with local practice), symptomatic congestive heart failure (CHF), myocardial infarction (MI) in last three months, or unstable angina pectoris, significant uncontrolled cardiac arrhythmia, clinically relevant liver cirrhosis, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirements
* Patient must not have received prior radiation therapy to \>= 25% of the bone marrow for other diseases
* Patient must not have received prior systemic anthracycline therapy
* NOTE: Patients who have received prior intravesical chemotherapy at any time for non-muscle invasive urothelial carcinoma of the bladder are eligible
* Patient must not have either history of or active autoimmune disease requiring immunosuppressive therapy within 2 years prior to registration/randomization or any history of inflammatory bowel disease (inflammatory bowel disease \[IBD\], colitis, or Crohn's disease), neuromuscular autoimmune condition, immune-related pneumonitis or interstitial lung disease. Patients with well-controlled hyper/hypothyroidism, celiac controlled by diet alone, diabetes mellitus type I, vitiligo, alopecia, psoriasis, eczema, lichen planus, or similar skin/mucosa condition are eligible
* Patient must not be on or have used immunosuppressive medication within 14 days prior to the first dose of durvalumab. The following are exceptions to this criterion:
* Intranasal, inhaled, intra-auricular, topical steroids, or local steroid injections (e.g. intra-articular injection
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent at the time of enrollment
* Steroids as premedications for hypersensitivity reactions (e.g. computed tomography \[CT\] scan premedication)
* Patient must not have received live attenuated vaccine within 30 days prior to the first dose of durvalumab, while on protocol treatment and within 30 days after the last dose of durvalumab
* Patient must not have had a major surgical procedure within 28 days prior to registration/randomization
* NOTE: Cystoscopy/ureteroscopy, stent placement or nephrostomy tube is not considered major surgery
* Patient must not have history of allogenic organ transplantation PROCEDURE: Biopsy, PROCEDURE: Biospecimen Collection, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Doxorubicin Hydrochloride, BIOLOGICAL: Durvalumab, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, BIOLOGICAL: Pegfilgrastim, PROCEDURE: Therapeutic Conventional Surgery, DRUG: Vinblastine Sulfate
Urinary Bladder, Renal Pelvis and Ureter Urothelial Carcinoma
UT Southwestern; Parkland Health & Hospital System
Comparing the New Anti-cancer Drug Eribulin With Chemotherapy Against the Usual Chemotherapy Alone in Metastatic Urothelial Cancer
This phase III trial compares the usual chemotherapy treatment to eribulin plus gemcitabine in treating patients with urothelial cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as eribulin, gemcitabine, docetaxel, paclitaxel, and sacituzumab govitecan work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial aims to see whether adding eribulin to standard of care chemotherapy may work better in treating patients with metastatic urothelial cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE3
NCT04579224
STU-2023-0199
Inclusion Criteria:
* Participant must have predominant histologically and cytologically proven urothelial carcinoma in a metastatic site
* Participant must have evidence of metastatic urothelial carcinoma based on CT or MRI within 28 days prior to registration
* Participant must have had progression of disease following prior therapy at the discretion of the treating investigator
* Participants must not require immediate central nervous system (CNS)-specific treatment, in the opinion of the treating investigator if they have active brain metastases (defined as new or progressive brain metastases) or leptomeningeal disease
* Participant must have had prior systemic therapy in metastatic setting that:
* Included enfortumab vedotin
* Included a PD1/PDL1 antibody
* NOTE: Under the discretion of the treating physician, participants who are not candidates for PD1/PDL1 antibody systemic therapy are allowed
* Any systemic therapy provided in adjuvant, neoadjuvant, or chemoradiation settings for urothelial carcinoma can be considered to be in metastatic setting, if the last day of treatment was within 12 months prior to the diagnosis of metastatic disease
* Participant must have completed any planned surgery or radiation therapy prior to registration
* Participant must not have unresolved toxicities from prior surgeries or radiation therapy \> grade 1 at the time of registration
* Participant must be ≥ 18 years of age
* Participant must have Zubrod performance status 0-2
* Participant must have history and physical examination within 28 days prior to registration
* Participant must have complete blood count (CBC), complete metabolic panel including liver function tests, and lactate dehydrogenase (LDH) obtained with 28 days prior to registration
* Participant must have adequate kidney function as evidenced by measured or calculated creatinine clearance \>= 20 mL/min within 28 days prior to registration
* Participant must have adequate hepatic function documented by either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =\< 3 x institutional upper limit of normal (IULN) within 28 days prior to registration. If both AST and ALT are performed, both must be =\< 3 x IULN. For participants with liver metastases, AST or ALT must be =\< 5 x IULN
* Participant must be on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to registration if they are known to have human immunodeficiency virus (HIV)-infection
* Participants must have undetectable hepatitis B virus (HBV) viral load within 28 days prior to registration if participant has known chronic hepatitis B virus (HBV) infection
* Participants with a known history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load within 28 days prior to registration
* Participants may have a prior or concurrent malignancy provided the natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen per the opinion of the treating investigator
* Participants must not be planning to take strong or moderate CYP3A or CYP2C8 inhibitors or inducers if randomized to Arm 1 and standard of care (SOC) regimen chosen is paclitaxel or docetaxel. Participants receiving strong or moderate CYP3A- or CYP2C8 inducers must discontinue use at least 2 weeks prior to randomization
* Participant must not have a known history of corrected QT (QTc) prolongation
* Participants must not be pregnant or nursing due to the risk of harm to a fetus or nursing infant. Women and men of reproductive potential must have agreed to use an effective contraceptive method for the course of the study and 6 months (females) or 3.5 months (males) after the last dose. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
* Participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Docetaxel, DRUG: Eribulin Mesylate, DRUG: Gemcitabine Hydrochloride, PROCEDURE: Magnetic Resonance Imaging, DRUG: Paclitaxel, BIOLOGICAL: Sacituzumab Govitecan
Metastatic Bladder Urothelial Carcinoma, Metastatic Renal Pelvis Urothelial Carcinoma, Metastatic Ureter Urothelial Carcinoma, Metastatic Urethral Urothelial Carcinoma, Metastatic Urothelial Carcinoma, Stage IV Bladder Cancer AJCC v8, Stage IVA Bladder Cancer AJCC v8, Stage IVB Bladder Cancer AJCC v8, Gall Bladder, Urinary Bladder, Stage IV Urethral Cancer AJCC v8, Refractory Bladder Urothelial Carcinoma, Refractory Renal Pelvis Urothelial Carcinoma, Refractory Ureter Urothelial Carcinoma, Refractory Urethral Urothelial Carcinoma, Refractory Urothelial Carcinoma, Stage IV Renal Pelvis and Ureter Cancer AJCC v8, Stage IV Renal Pelvis Cancer AJCC v8, Stage IV Ureter Cancer AJCC v8
UT Southwestern; Parkland Health & Hospital System
Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial (PROBE)
This phase III trial compares the effect of adding surgery to a standard of care immunotherapy-based drug combination versus a standard of care immunotherapy-based drug combination alone in treating patients with kidney cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, pembrolizumab, and avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Surgery to remove the kidney, called a nephrectomy, is also considered standard of care; however, doctors who treat kidney cancer do not agree on its benefits. It is not yet known if the addition of surgery to an immunotherapy-based drug combination works better than an immunotherapy-based drug combination alone in treating patients with kidney cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE3
NCT04510597
STU-2021-0266
Inclusion Criteria:
* STEP 1 REGISTRATION: Participants must have a histologically proven diagnosis of clear cell or non-clear cell renal cell carcinoma. Participants with collecting duct carcinoma histology are not eligible. Participants with multifocal or bilateral tumors are eligible
* STEP 1 REGISTRATION: Participants must have primary tumor in place
* STEP 1 REGISTRATION: Participants must have the following scans performed, showing clinical evidence of measurable or non-measurable metastatic disease:
* Computed tomography (CT) scan of the chest (can be performed without contrast if CT contrast cannot be given)
* CT of abdomen and pelvis with contrast OR magnetic resonance imaging (MRI) of the abdomen and pelvis with or without contrast
Scans must be performed within the following timeframes:
* Treatment naive participants must have scans documenting metastatic disease completed within 90 days prior to study registration
* Previously treated participants must have scans documenting metastatic disease completed within 90 days prior to first dose of systemic treatment
* STEP 1 REGISTRATION: Participants with symptomatic metastases may have received palliative radiotherapy or receive palliative radiotherapy after registration
* STEP 1 REGISTRATION: Participants must have no clear contraindications to nephrectomy
* STEP 1 REGISTRATION: Participants must be offered the opportunity to participate in specimen bank. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* STEP 1 REGISTRATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* STEP 1 REGISTRATION: As part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
* STEP 2 REGISTRATION: Participants must have at least one of the following scans performed 12 weeks (+/- 2 weeks) after starting pre-randomization treatment
* CT scan of the chest (can be performed without contrast if CT contrast cannot be given)
* CT of abdomen and pelvis with contrast OR MRI of the abdomen and pelvis with or without contrast Scans must be performed within 28 days prior to randomization. Response should be assessed by comparing with a CT or MRI of the chest, abdomen and pelvis obtained prior to starting pre-randomization treatment. Participants with complete response in all metastatic sites are not eligible to randomize to Step 2
• STEP 2 REGISTRATION: Participants must have one of the following objective statuses after 12 weeks of pre-randomization treatment
* Stable disease
* Partial response
* The treating investigator believes the patient is deriving clinical benefit from systemic therapy AND have Zubrod performance status 0-1
* STEP 2 REGISTRATION: Participants must plan to continue the immune-based therapy received during pre-randomization treatment
* STEP 2 REGISTRATION: Participants must be randomized on or between the 11th and 14th week of protocol-directed pre-randomization treatment therapy
* STEP 2 REGISTRATION: Participants must have received at least one of the minimum amounts of immunotherapy:
* 2 infusions of nivolumab + 1 infusion of ipilimumab
* 2 infusions of pembrolizumab
* 2 infusions of avelumab
* STEP 2 REGISTRATION: Participants must have a planned surgery date within 42 days of randomization
* STEP 2 REGISTRATION: Participants must be a surgical candidate as determined by study urologist. The urology consult should be done within 42 days prior to randomization
* STEP 2 REGISTRATION: Participants must have a complete physical examination and medical history within 28 days prior to randomization
* STEP 2 REGISTRATION: Participants must have a Zubrod performance status of 0-1 within 28 days prior to randomization
* STEP 2 REGISTRATION: Total bilirubin =\< institutional upper limit of normal (ULN) (within 28 days prior to randomization)
* STEP 2 REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 3 x institutional upper limit of normal (ULN) (within 28 days prior to randomization)
* STEP 2 REGISTRATION: Serum creatinine =\< 1.5 x the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance \>= 50 mL/min using the Cockcroft-Gault Formula) (must have been drawn and processed within 28 days prior to randomization)
Exclusion Criteria:
* STEP 1 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
* STEP 1 REGISTRATION: Participants must not have received the following prior treatment of metastatic renal cell carcinoma:
* Treatment naive participants must not have received any prior lines of systemic therapy for metastatic renal cell carcinoma beyond the line intended as part of protocol therapy
* Previously treated participants must not have received any systemic therapy for metastatic renal cell carcinoma beyond the one regimen received off protocol as specified in Step 1 pre-randomization treatment
* STEP 1 REGISTRATION: Participants must not have received more than the following amounts protocol-directed pre-randomization treatment:
* Treatment naive participants must not have received any pre-randomization treatment.
* Previously treated participants must not be planning to receive any additional treatment prior to Step 2 randomization, and must not have received more than the following amounts of pre-randomization treatment:
* 4 infusions of nivolumab
* 4 infusions of ipilimumab
* 4 infusions of pembrolizumab
* 7 infusions of avelumab
* STEP 1 REGISTRATION: Participants must not have received immunotherapy for any cancer within the following timeframes:
* Treatment naive participants must not have received any immunotherapy within a year of registration
* Previously treated participants must not have received any other immunotherapy within a year of the start of off protocol specified pre-randomization treatment
* STEP 1 REGISTRATION: Participants must not have a solitary kidney and not have a transplanted kidney
* STEP 1 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, any in situ or T1 cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for at least two years
* STEP 1 REGISTRATION: Participants must not have been previously diagnosed with a medical condition that makes them ineligible for immune based combination therapy or nephrectomy
* STEP 2 REGISTRATION: Participants must not show progression in the primary tumor. Participants who are considered to have pseudo progression are allowed
* STEP 2 REGISTRATION: Participants must not have known active brain metastases. Participants with previously treated brain metastases are eligible if participant has no neurologic signs or symptoms suggestive of brain metastasis. Brain imaging studies are not required. If brain imaging studies are performed, they must be negative for disease
* STEP 2 REGISTRATION: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years PROCEDURE: Cytoreductive Nephrectomy, DRUG: Active Comparator
Metastatic Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Kidney
UT Southwestern
Combination of Novel Therapies for CKD Comorbid Depression (CONCORD)
The overall goal of the study is to determine if treatment of a Major Depressive Disorder (MDD) improves the outcomes of patients with chronic kidney disease (CKD). We showed that MDD is present in 25% of CKD patients and independently associated with progression to End-Stage Kidney Disease, hospitalization, and death. Depression is also associated with lower quality of life (QOL), fatigue, poor sleep, and non-adherence to diet and medications. However, evidence for efficacy and tolerability of commonly-used antidepressant medications or nonpharmacologic treatments are limited in CKD patients. Our group was the first to conduct a double-blind randomized controlled trial for MDD treatment in 201 patients with non-dialysis CKD, and showed that sertraline, a commonly used selective serotonin reuptake inhibitor (SSRI), was no more efficacious than placebo for improving depressive symptoms. It becomes imperative to test novel strategies to treat MDD in CKD. We propose to compare with a control group, the efficacy and tolerability of two novel treatment strategies - (1) Behavioral Activation Teletherapy (BAT) for 16 weeks, with the addition of bupropion, a non-SSRI antidepressant, at 8 weeks for patients whose depression has not remitted (non-remitters); and (2) bupropion for 16 weeks, with the addition of BAT at 8 weeks for non-remitters. In Aim 1, we will investigate the efficacy and tolerability of these 2 strategies vs. control for improvement in a primary endpoint of depressive symptoms in 201 patients (67 per group) with non-dialysis CKD stages 3b-5 and MDD at 2 sites, randomized 1:1:1 to either strategy or a control group of Clinical Management plus placebo. We hypothesize that either approach vs. control will result in a minimal clinically important difference of 2 points improvement in depressive symptoms, as ascertained blindly by the Quick Inventory of Depressive Symptomatology. In Aim 2 we will investigate the efficacy and tolerability of 8 weeks of (1) single-blind BAT plus placebo or (2) double-blind bupropion plus Clinical Management vs. control for improvement in depressive symptoms. In Aim 3, we will compare the efficacy of these 2 treatments strategies vs. control for improvement in CKD patient-centered outcomes including a. adherence to medications and healthcare visits; b. fatigue; c. sleep; and d. overall functioning. A clinical trial is urgently needed to address the evidence gap that exists for MDD treatment in CKD patients.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Ana.Arroyo@UTSouthwestern.edu
Meredith McAdams
All
18 Years and over
Phase 2
NCT04422652
STU-2020-0046
Inclusion Criteria:
• Male or female adults aged 18 years or greater. There will be no upper age limit.
• Presence of CKD stages 3b, 4 or non-dialysis stage 5, with an estimated glomerular filtration rate (GFR) of <45 mL/min/1.73 m2 for a period of at least 3 months, as defined by the National Kidney Foundation and determined using the four-variable Modification of Diet for Renal Diseases Study formula.
• Presence of a current Major Depressive Disorder (MDD) based on MINI DSM IV-based criteria
• Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR) score of ≥11 at enrollment and ≥11 on QIDS-Clinician Rated (QIDS-C) at randomization.
• Able to understand and sign informed consent after the nature of the study has been fully explained
• Kidney transplant patients that are at least 6 month post-transplantation (3 months post-transplant, with at least another 3 months to confirm eGFR <45)
Exclusion Criteria:
• Unable to understand or give informed consent.
• Unwilling or unable to participate in the protocol or comply with any of its components
• Receiving chronic dialysis
• Significant hepatic dysfunction or liver enzyme abnormalities 3 times or greater than the upper limit of normal
• Terminal chronic obstructive pulmonary disease or cancer
• Presence of seizure disorder
• Current use of class I anti-arrhythmic medications (such as 1C propafenone and flecanide), pimozide, MAO inhibitors, reserpine, guanethidine, cimetidine, or methyldopa; tri-cyclic anti-depressants, neuroleptics, or anti-convulsants
• Use of serotonergic drugs or supplements such as triptans, tramadol, linezolid, tryptophan, and St. John's Wort.
• Use of medications known to cause QT prolongation on EKG
• Ongoing use of antidepressant medications for depression treatment
• Past treatment failure on bupropion
• Initiation of depression-focused psychotherapy in the 3 months prior to study entry
• Active alcohol or substance abuse or dependence that requires acute detoxification at study entry
• Present or past psychosis or Bipolar I or II disorder
• Dementia or a Mini-Mental State Examination score <23
• Active suicidal intent
• Pregnancy, lactation, or women of childbearing potential not willing to use adequate contraception
Drug: Bupropion, Behavioral: Behavioral activation therapy, Drug: Placebo, Other: Clinical Management
Major Depressive Disorder, Chronic Kidney Diseases, Kidney
UT Southwestern; Parkland Health & Hospital System
Pathogenesis of Uric Acid Nephrolithiasis: Role of Pioglitazone/Weight Loss
The investigators will randomize overweight and obese iuan patients to Pio (45 mg/day, highest approved dose or placebo), WL (10% of body weight, following the established program used in the Diabetes Prevention Program), or Pio+WL. Participants will be evaluated at baseline and after 24 weeks of intervention while on a fixed metabolic diet to exclude the confounding effects of diet and perspiration. The primary endpoint will be change in upH, and multiple additional endpoints (serum, urine, imaging) will be assessed.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Sudeepa.Bhattacharya@UTSouthwestern.edu
Khashayar Sakhaee
ALL
21 Years to 99 Years old
PHASE4
NCT04370093
STU-2019-0907
Inclusion Criteria:
Idiopathic uric acid nephrolithiasis, with last stone analysis showing that stone has \>90% uric acid in composition Age \>21 years Any gender, race/ethnicity (from weight loss), but weight \<165 Kg (to fit into MR instrument); eGFR\>60ml/min/1.73 m2
Exclusion Criteria:
Bariatric surgery, chronic diarrhea, recurrent UTIs current insulin use use of a thiazolidinedione in past 2 years contraindication to thiazolidinedione use (liver dz, pedal edema, CHF NYHA class III/IV, no contraception) Bladder cancer Use of SGLT2-i, GLP-1 analogs, gemfibrozil, topiramate, rifampin Hba1c \> 8.5% DRUG: Pioglitazone 45 mg, BEHAVIORAL: Weight Loss, OTHER: Pioglitazone + Weight Loss
Nephrolithiasis, Uric Acid
Biomedical Sciences
Parkland Health & Hospital System
A Study of Combination Chemotherapy for Patients With Newly Diagnosed DAWT and Relapsed FHWT
This phase II trial studies how well combination chemotherapy works in treating patients with newly diagnosed stage II-IV diffuse anaplastic Wilms tumors (DAWT) or favorable histology Wilms tumors (FHWT) that have come back (relapsed). Drugs used in chemotherapy regimens such as UH-3 (vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan) and ICE/Cyclo/Topo (ifosfamide, carboplatin, etoposide, cyclophosphamide, and topotecan) work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help doctors find out what effects, good and/or bad, regimen UH-3 has on patients with newly diagnosed DAWT and standard risk relapsed FHWT (those treated with only 2 drugs for the initial WT) and regimen ICE/Cyclo/Topo has on patients with high and very high risk relapsed FHWT (those treated with 3 or more drugs for the initial WT).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Jonathan Wickiser
ALL
up to 30 Years old
PHASE2
NCT04322318
STU-2020-1103
Inclusion Criteria:
* Patients with newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN03B2 and have received an initial risk assignment showing DAWT (if anaplasia first identified at diagnostic, pre-treatment nephrectomy or biopsy) or a delayed nephrectomy classification showing DAWT (if anaplasia first noted at delayed nephrectomy) prior to enrollment on AREN1921. Prior enrollment on AREN03B2 is not an eligibility requirement for patients with relapsed favorable histology Wilms tumor.
* Patients must be =\< 30 years old at study enrollment
* Patients with the following diagnoses are eligible for this study:
* Newly diagnosed stages 2 - 4 diffuse anaplastic Wilms tumor as confirmed by central review
* Favorable histology Wilms tumor at first relapse. Relapsed FHWT patients must have previously achieved remission for their initial FHWT diagnosis to be eligible for this study. The relapse risk groups are defined as follows, regardless of radiation therapy:
* Standard-Risk relapse: Patients who received two chemotherapy agents for frontline therapy; primarily actinomycin D and vincristine
* High-Risk relapse: Patients who received three chemotherapy agents for frontline therapy; primarily vincristine, actinomycin D and doxorubicin or vincristine, actinomycin D and irinotecan
* Very High-Risk relapse: Patients who received four or more chemotherapy agents as part of initial therapy; primarily regimen M or its variations
* Patients with newly diagnosed DAWT must have had histologic verification of the malignancy. For relapsed FHWT patients, biopsy to prove recurrence is encouraged, but not required
* Note: For relapsed FHWT patients, an institutional pathology report confirming favorable histology Wilms tumor (from relapse, if available, or from original diagnosis) must be available for upload prior to initiation of protocol therapy
* Patients with newly diagnosed Stages 2 - 4 diffuse anaplastic Wilms tumor must be enrolled on AREN1921 within 2 weeks of the tumor-directed surgery or biopsy procedure that first confirms a diagnosis of DAWT, whether at initial diagnostic procedure or delayed nephrectomy (such surgery/biopsy is day 0). For patients who received prior therapy for presumed favorable histology Wilms tumor, later confirmed to have diffuse anaplastic Wilms tumor at subsequent review of the initial biopsy
* Patients with newly diagnosed DAWT who undergo upfront nephrectomy must have at least 1 lymph node sampled prior to study enrollment
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have a life expectancy of \>= 8 weeks
* Diffuse Anaplastic Wilms Tumor: Patients with diffuse anaplastic histology must have had no prior systemic therapy, except in the following situations:
* Patients with diffuse anaplastic Wilms tumor who received no more than 12 weeks of pre nephrectomy chemotherapy for what was originally presumed to be favorable histology Wilms tumor, subsequently confirmed to be diffuse anaplastic Wilms tumor at delayed nephrectomy
* Patients with diffuse anaplastic Wilms tumor who received no more than 6 weeks of chemotherapy following upfront biopsy, initiated within 14 days of biopsy, for presumed favorable histology Wilms tumor based on institutional review, but subsequently corrected to diffuse anaplastic Wilms tumor based on the AREN03B2 initial risk assignment results (if available per current version of AREN03B2)
* Treatment consisting of vincristine/doxorubicin/cyclophosphamide initiated on an emergent basis and within allowed timing as described
* Note: Patients who received prior therapy for presumed favorable histology Wilms tumor, later identified to have diffuse anaplastic Wilms tumor as per above, must begin study treatment starting at cycle 3 (week 7) of regimen UH 3. Patients who received emergency radiation to preserve organ function are eligible as noted. Patients who received radiation as part of standard of care for presumed newly diagnosed favorable histology Wilms tumor, along with chemotherapy as noted above, prior to identification of diffuse anaplasia, are also eligible
* Relapsed Favorable Histology Wilms Tumor: Patients must not have received prior chemotherapy for their relapsed favorable histology Wilms tumor diagnosis. In addition, patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
* Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study
* Radiation therapy (RT): \>= 2 weeks (wks) must have elapsed for local palliative RT (small port); \>= 6 months must have elapsed if prior craniospinal RT or if \>= 50% radiation of pelvis; \>= 6 wks must have elapsed if other substantial bone marrow (BM) radiation. Patients with relapsed favorable histology Wilms tumor who received emergency radiation to preserve organ function are eligible and do not need to washout with the above criteria
* Patients may not be receiving any other investigational agents (within 4 weeks prior to study enrollment)
* Peripheral absolute neutrophil count (ANC) \>= 750/uL (performed within 7 days prior to enrollment)
* Platelet count \>= 75,000/uL (transfusion independent) (performed within 7 days prior to enrollment)
* Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions) (performed within 7 days prior to enrollment)
* Patients with high-risk or very high-risk relapsed FHWT who will be treated with regimen ICE/Cyclo/Topo, must have renal function assessed by creatinine clearance or radioisotope glomerular filtration rate (GFR) and meet the following requirement:
* Creatinine clearance or radioisotope GFR \>= 60 mL/min/1.73 m\^2 (performed within 7 days prior to enrollment)
* Patients diagnosed with stage 2-4 DAWT or standard risk relapsed FHWT, who will be treated with regimen UH 3, may either obtain a creatinine clearance, radioisotope GFR (meeting the above criteria of GFR \>= 60 mL/min/1.73 m\^2), or an adequate serum creatinine as per the following table:
* Age: Maximum Serum Creatinine (mg/dL)
* 1 month to \< 6 months: 0.4 (male and female)
* 6 months to \< 1 year: 0.5 (male and female)
* 1 to \< 2 years: 0.6 (male and female)
* 2 to \< 6 years: 0.8 (male and female)
* 6 to \< 10 years: 1 (male and female)
* 10 to \< 13 years: 1.2 (male and female)
* 13 to \< 16 years: 1.5 (male), 1.4 (female)
* \>= 16 years: 1.7 (male), 1.4 (female)
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) for age or direct bilirubin =\< ULN for patients whose total bilirubin \> 1.5 x ULN (performed within 7 days prior to enrollment)
* Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 x upper limit of normal (ULN) for age or =\< 5 x ULN for patients with liver metastases (performed within 7 days prior to enrollment)
* Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by radionuclide angiogram (obtained within 21 days prior to enrollment and start of protocol therapy)
Exclusion Criteria:
* Patients with a history of bilateral Wilms tumor (synchronous or metachronous)
* Patients with any uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, or symptomatic congestive heart failure (defined as grade 2 or higher heart failure per Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0)
* Relapsed FHWT patients who did not receive frontline chemotherapy (e.g., very low risk FHWT initially observed without chemotherapy) or received only one chemotherapy agent for frontline therapy
* For patients with high-risk or very high-risk relapsed FHWT:
* Patients with renal tubular acidosis (RTA) as evidenced by serum bicarbonate \< 16 mmol/L and serum phosphate =\< 2 mg/dL (or \< 0.8 mmol/L) without supplementation
* For stages 2-4 DAWT and standard-risk relapsed FHWT patients:
* Chronic inflammatory bowel disease and/or bowel obstruction
* Concomitant use of St. John's wort, which cannot be stopped prior to the start of trial treatment
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation PROCEDURE: Biopsy, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Carboplatin, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Doxorubicin, DRUG: Etoposide, DRUG: Ifosfamide, DRUG: Irinotecan, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, RADIATION: Radiation Therapy, PROCEDURE: Surgical Procedure, DRUG: Topotecan, PROCEDURE: Transabdominal Ultrasound, DRUG: Vincristine, PROCEDURE: X-Ray Imaging
Stage II Kidney Wilms Tumor, Stage III Kidney Wilms Tumor, Stage IV Kidney Wilms Tumor, Recurrent Kidney Wilms Tumor, Anaplastic Kidney Wilms Tumor, Kidney
Children’s Health
Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Standard of Care (POPS) (POPS or POP02)
The study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Aruna.Ayalasomayajula@UTSouthwestern.edu
Mia Maamari
ALL
0 Years to 20 Years old
NCT04278404
STU-2021-0176
Inclusion Criteria:
• Participant is \< 21 years of age
• Parent/ Legal Guardian/ Adult Participant can understand the consent process and is willing to provide informed consent/HIPAA:
• (a) Participant is receiving one or more of the study drugs of interest at the time of enrollment or (b) Participant is NOT receiving one or more of the study drugs of interest but is SARS-COV-2 positive within 60 days prior to enrollment
Exclusion Criteria:
• Participant has a known pregnancy Below exclusion criteria apply only to: Participants receiving one or more of the study drugs of interest at the time of enrollment, DOI administration or PK sampling: (Refer to DOI specific appendices for details on enrollment cohort specifications and additional eligibility criteria)
• Has had intermittent dialysis within previous 24 hours
• Has had a kidney transplant within previous 30 days
• Has had a liver transplant within previous 1 year
• Has had a stem cell transplant within previous 1 year
• Has had therapeutic hypothermia within previous 24 hours
• Has had plasmapheresis within the previous 24 hours
• Has a Ventricular Assist Device
• Has any condition which would make the participant, in the opinion of the investigator, unsuitable for the study
DRUG: The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care:
Bronchopulmonary Dysplasia, Heart Failure, Pulmonary Arterial Hypertension, Hypertension, Hyperphosphatemia, Pain, Pneumonia, Insomnia, Menorrhagia, Down Syndrome, Hemophilia, Fibrinolysis, Hemorrhage, Coronavirus Infection (COVID-19), Urinary Tract Infections in Children, Primary Hyperaldosteronism, Edema, Hypokalemia, Skin Infection, Arrythmia, Asthma in Children, Adrenal Insufficiency, Attention Deficit Hyperactivity Disorder, Multisystem Inflammatory Syndrome in Children (MIS-C), Kawasaki Disease, Coagulation Disorder
Children’s Health
A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
Phase 1 will evaluate the safety and tolerability at different dose levels of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring anaplastic lymphoma kinase (ALK), receptor tyrosine kinase encoded by the gene ROS1 (ROS1), or neurotrophic receptor kinase genes encoding TRK kinase family (NTRK1-3) alterations to estimate the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) and select the Pediatric Recommended Phase 2 Dose (RP2D). Phase 2 will determine the anti-tumor activity of repotrectinib in pediatric and young adult subjects with advanced or metastatic malignancies harboring ROS1 or NTRK1-3 alterations.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tanya Watt
ALL
up to 25 Years old
PHASE1
NCT04094610
STU-2019-1268
Key
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
• Cohort Specific
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
Inclusion Criteria:
• Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• Phase 1: Age \<12 years; Phase 2: Age 12- 25 years
• Prior cytotoxic chemotherapy is allowed.
• Prior immunotherapy is allowed.
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollment.
• Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
Inclusion Criteria:
• Cohort Specific
Inclusion Criteria:
* Cohort 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
* Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
* Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable disease.
• Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment. Key Exclusion Criteria (Phase 1 and Phase 2):
• Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.
• Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• Any of the following cardiac criteria: * Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screening clinic ECG machine-derived QTc value * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \> 250 msec) * Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• Peripheral neuropathy of CTCAE ≥grade 2.
• Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• Any potential allergies to repotrectinib and/or its excipients.
DRUG: Oral repotrectinib (TPX-0005)
Lymphoma, Locally Advanced Solid Tumors, Metastatic Solid Tumors, Primary CNS Tumors, Breast - Female, Breast - Male, Colon, Kidney, Lung/Thoracic, Rectum, Thyroid, Urinary Bladder, Soft Tissue
ALK, ROS1, NTRK1-3, Primary CNS tumor, anaplastic large cell lymphoma, metastatic solid tumor, advanced solid tumor, sarcoma, infantile fibrosarcoma, glioblastoma, soft tissue schwannoma, solitary fibrous tumor, glioma, inflammatory myofibroblastic tumor, pediatric
Children’s Health
Testing the Addition of a New Anti-cancer Drug, Radium-223 Dichloride, to the Usual Treatment (Cabozantinib) for Advanced Renal Cell Cancer That Has Spread to the Bone, RadiCaL Study
This phase II trial studies whether adding radium-223 dichloride to the usual treatment, cabozantinib, improves outcomes in patients with renal cell cancer that has spread to the bone. Radioactive drugs such as radium-223 dichloride may directly target radiation to cancer cells and minimize harm to normal cells. Cabozantinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving radium-223 dichloride and cabozantinib may help lessen the pain and symptoms from renal cell cancer that has spread to the bone, compared to cabozantinib alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE2
NCT04071223
STU-2020-0639
Inclusion Criteria:
* Documented histologic or cytologic diagnosis of renal cell cancer (RCC). All subtypes of RCC are eligible including but not limited to clear cell, papillary, chromophobe, translocation, collecting duct carcinoma, medullary carcinoma, and unclassified categories. Enrollment of non-clear cell patients will be limited to 20% of the total sample size (\~ 42 patients). Once this goal is met, accrual of non-clear cell patients will be discontinued (a notice will be sent out 2 weeks in advance). Sarcomatoid and rhabdoid differentiation are allowed
* Presence of at least 1 metastatic bone lesion not treated with prior radiation is required.
* The presence of bone metastases can be detected by computed tomography (CT), magnetic resonance imaging (MRI), Tc-99m bone scan or positron emission tomography (PET) (fludeoxyglucose F-18 \[FDG\] or sodium fluoride \[NaF\]) imaging. Patients with non-measurable bone-only disease are allowed. Patients may have received prior radiation therapy for bone metastases or other external radiation \>= 7 days prior to registration, as long as they still have at least 1 metastatic bone lesion not treated with radiation. Patients with visceral metastases are allowed, as long as they have at least one untreated bone metastases
* No prior treatment with cabozantinib
* No treatment with any type of small molecular kinase inhibitor (including investigational kinase inhibitors) within 2 weeks or 5 half-lives (whichever is shorter) of registration or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of registration
* No prior hemibody external radiotherapy
* No prior therapy with radium-223 dichloride or systemic radiotherapy (such as samarium, strontium)
* No major surgery within 6 weeks of randomization. Procedures such as thoracentesis, paracentesis, percutaneous biopsy, Moh's or other topical skin surgery, Lasik eye surgery are not considered major surgery. Patients who have had a nephrectomy may be registered \>= 3 weeks after surgery, providing there are no wound-healing complications. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
* Recovery to baseline or =\< grade 1 CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy
* The use of osteoclast targeted therapy including either bisphosphonates or denosumab is mandated on this study except in patients with contraindications as determined by the treating investigator, including:
* Hypocalcemia
* Hypophosphatemia
* Renal impairment including those with a glomerular filtration rate (GFR) \< 35 mL/min using the Cockcroft-Gault equation or acute renal impairment
* Hypersensitivity to drug formulation
* Dental condition or need for dental intervention that per the investigator would increase the risk of osteonecrosis of jaw (ONJ).
* Use of osteoclast targeted therapy or reason against use needs to be recorded in the electronic case report form (eCRF). Additionally, reason for discontinuation of osteoclast targeted therapy need to be appropriately documented in the eCRF
* Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown.
* Therefore, for women of childbearing potential only, a negative urine pregnancy test done =\< 28 days prior to registration is required. A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
* Age \>= 18 years
* Karnofsky performance status \>= 60%
* No brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
* No imminent or established spinal cord compression based on clinical symptoms and/or imaging. In patients with untreated imminent or established spinal cord compression, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
* No imminent or impending pathologic fracture based on clinical symptoms and/or imaging. In patients with untreated imminent or impending pathologic fracture, treatment with standard of care as clinically indicated should be completed at least 2 weeks before registration
* No significant, uncontrolled intercurrent or recent illness, including but not limited to the following conditions:
* Cardiovascular disorders: Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia; uncontrolled hypertension defined as sustained blood pressure \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment; stroke (including transient ischemic attack), myocardial infarction, or other ischemic event, within 6 months before randomization; thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 1 month before randomization
* Gastrointestinal disorders: Disorders associated with a high risk of perforation or fistula formation: active inflammatory bowel disease, active diverticulitis, active cholecystitis, active symptomatic cholangitis or active appendicitis, active acute pancreatitis or active acute obstruction of the pancreatic or biliary duct, or active gastric outlet obstruction; abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 3 months before randomization. Note: Complete healing of an intra-abdominal abscess must be confirmed before randomization
* No clinically significant hematuria, hematemesis, or hemoptysis, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 3 months before randomization
* No lesions invading major pulmonary blood vessels
* No other clinically significant disorders:
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]) with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy (with no medications prohibited by this protocol \[e.g. drug-drug interactions\]), if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load (with no medications prohibited by this protocol \[e.g. drug-drug interactions\])
* No serious non-healing wound or ulcer
* No malabsorption syndrome
* No uncompensated/symptomatic hypothyroidism
* No moderate to severe hepatic impairment (Child-Pugh B or C)
* No requirements for hemodialysis or peritoneal dialysis
* No history of solid organ transplantation
* No chronic concomitant treatment with strong CYP3A4 inducers or inhibitors. Because the list of these agents is constantly changing, it is important to regularly consult a frequently updated medical reference. Patients may not have received a strong CYP3A4 inducer within 12 days prior to registration nor a strong CYP3A4 inhibitor within 7 days prior to registration
* No concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants include:
* Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
* Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
* Absolute neutrophil count (ANC) \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 9 g/dl (transfusions allowed)
* Calculated (calc.) creatinine clearance \>= 30 mL/min using the Cockcroft-Gault equation
* Total bilirubin =\< 1.5 x upper limit of normal (ULN), for patients with Gilberts disease =\< 3.0 x ULN
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 x ULN
* Urine protein to creatinine (UPC) ratio =\< 2 mg/mg OR 24-hr urine protein \< 2 g PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabozantinib S-malate, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, OTHER: Questionnaire Administration, RADIATION: Radium Ra 223 Dichloride
Advanced Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma, Papillary Renal Cell Carcinoma, Metastatic Malignant Neoplasm in the Bone, Unclassified Renal Cell Carcinoma, Chromophobe Renal Cell Carcinoma, Kidney Medullary Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Kidney, Collecting Duct Carcinoma
UT Southwestern
A Study to Evaluate Safety, Efficacy and Pharmacokinetics of Paricalcitol For Treatment of Secondary Hyperparathyroidism (SHPT) in Pediatric Participants With Stage 5 Chronic Kidney Disease (CKD)
The main objective of this study is to evaluate the safety, efficacy and pharmacokinetics of paricalcitol oral solution in pediatric participants of ages 0 to 9 years with SHPT associated with stage 5 CKD receiving Peritoneal Dialysis (PD) or Hemodialysis (HD). The 24-week study is divided into two 12-week dosing periods (Dosing Period 1 followed by Dosing Period 2).
Call 214-648-5005
studyfinder@utsouthwestern.edu, melaku.lemma@childrens.com
Raymond Quigley
ALL
0 Years to 9 Years old
PHASE3
NCT04064827
STU-2019-1512
Inclusion Criteria:
* Participant is currently diagnosed with and/or being treated for secondary hyperparathyroidism (SHPT).
* Participant must be diagnosed with chronic kidney disease (CKD) stage 5 receiving peritoneal dialysis (PD) or hemodialysis (HD) for at least 30 days prior to initial Screening.
* For entry into the Washout Period (for vitamin D receptor activator \[VDRA\] non-naive participants), the participant must meet the appropriate laboratory criteria based upon the participant's age as described in the protocol.
* For entry into the Dosing Period (for VDRA-naive participants or VDRA non-naive participants who have completed the Washout Period), the participant must meet the appropriate laboratory criteria based upon the participant's age as described in the protocol.
Exclusion Criteria:
* Participant is scheduled to receive a living donor kidney transplant within 3 months of Screening or is a kidney transplant recipient.
* Participant is expected to discontinue peritoneal dialysis (PD) or hemodialysis (HD) within 3 months of the initial Screening visit.
* Participant has had a parathyroidectomy within 12 weeks prior to Screening.
* Participant is taking maintenance calcitonin, bisphosphonates, glucocorticoids (in a dose equivalent to more than \> 0.16 mg/kg/day or 5 mg prednisone/day, whichever is lower), 4 weeks prior to Dosing.
* Participant is receiving calcimimetics at the time of Screening or is expected to initiate calcimimetics at any time throughout the study.
* Participant is unable to take oral medications. DRUG: Paricalcitol
Chronic Kidney Disease (CKD), Secondary Hyperparathyroidism (SHPT), Thyroid
Chronic Kidney Disease, Paricalcitol, Hyperparathyroidism, Pediatric Subjects, Peritoneal Dialysis (PD), Hemodialysis (HD), Intact parathyroid hormone (iPTH)
Children’s Health
89Zr-DFO-Atezolizumab ImmunoPET/CT in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma
This is an exploratory clinical trial to assess the potential of 89Zr-DFO-Atezolizumab Positron Emission Tomography/Computed Tomography (PET/CT) scans in patients with locally advanced or metastatic renal cell carcinoma (RCC). This open label, nontherapeutic trial will test the correlation of 89Zr-DFO-Atezolizumab immunoPET/CT with programmed death-ligand 1 (PD-L1) expression and the response to immune checkpoint inhibitor therapy in patients with RCC. There will be two cohorts, one made up of patients with localized RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to nephrectomy and a second cohort of patients with metastatic RCC who will undergo 89Zr-DFO-Atezolizumab PET/CT prior to treatment with an immune checkpoint inhibitor.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
James Brugarolas
ALL
18 Years and over
PHASE2
NCT04006522
STU-2019-0714
Inclusion Criteria:
* Patients with suspected renal cell carcinoma with planned surgery or patients with metastatic RCC and a tissue diagnosis. (In standard clinical practice, biopsy is not routinely performed in patients who will be having surgery).
* Ability to understand and the willingness to sign a written informed consent.
* Patient must be able to lie still for a 30 to 60 minute PET/CT scan.
* One of the following:
• Patients with locally advanced RCC planned for surgery determined to be a high risk of recurrence, defined by presence of at least clinical T2 or TxN1, OR patients with metastatic RCC for whom treatment with cytoreductive nephrectomy and/or metastasectomy is planned by the treating physician.
• Patients with metastatic RCC for whom immuno-oncology (IO) therapy is planned. * Women of child-bearing potential must agree to undergo and have documented a negative pregnancy test on the day of 89Zr-DFO-Atezolizumab administration. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: * Has not undergone a hysterectomy or bilateral oophorectomy; or * Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
* History of severe allergic, anaphylactic, or other hypersensitivity reactions to atezolizumab or any other chimeric or humanized antibodies.
* Uncontrolled severe and irreversible intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
* Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
* Significant autoimmune disease requiring treatment with either prednisone (or steroid equivalent) at a dose \> 10 mg/day or other immunosuppressive agents. (Replacement steroid therapy is acceptable).
* Any patient for whom ICI therapy would be contraindicated for other reasons. Patients with adverse reactions to ICI therapy may undergo second 89Zr-DFO-Atezolizumab injection and PET/CT at the discretion of the treating physician considering that the dose of antibody represents 1% of a single therapeutic dose and therefore unlikely to cause adverse events.
* Subjects unable to provide informed consent.
* Subjects who are claustrophobic or have other contraindications to PET/CT.
* Subjects must not weigh more than the maximum weight limit for the table for the PET/CT scanner where the study is being performed. (\>200 kg or 440 lbs). DRUG: 89Zr-DFO-Atezolizumab, PROCEDURE: Positron Emission Tomography/Computed Tomography
Renal Cell Carcinoma, Kidney
renal cell carcinoma, atezolizumab, PET/CT
UT Southwestern; Parkland Health & Hospital System