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A Dose Escalation and Dose Expansion Study of Intratumoral ONM-501 Alone and in Combination With Cemiplimab in Patients With Advanced Solid Tumors and Lymphomas. (ON-5001)
A phase 1, multicenter, open label, non-randomized dose escalation and dose expansion study to examine the maximum tolerated dose, (MTD), minimum effective dose (MED) and/or recommended dose for expansion (RDE) of intratumoral ONM-501 as monotherapy and in combination with a PD-1 checkpoint inhibitor in patients with advanced solid tumors and lymphomas.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Heather McArthur
195731
All
18 Years and over
Phase 1
NCT06022029
STU-2023-0921
Inclusion Criteria:
• Ability to understand and willingness to sign written informed consent before performance of any study procedures
• Age ≥ 18 years
• Participants with solid tumors or lymphomas, confirmed by available histopathology records or current biopsy, that are advanced, nonresectable, or recurrent and progressing since last antitumor therapy, and for which no alternative standard therapy exists.
• Participants must have a minimum of one injectable and measurable lesion.
• Participants with prior Hepatitis B or C are eligible if they have adequate liver function
• Participants with human immunodeficiency virus (HIV) are eligible if on established HAART for a minimum of 4 weeks prior to enrollment, have an HIV viral load <400 copies/mL, and have CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
• Adequate bone marrow function:
• Adequate liver function
Exclusion Criteria:
Patients will be excluded from this study if they meet any of the
following criteria (Part 1a and Part 1b).
• Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has completed curative therapy.
• Major surgery within 4 weeks before the first dose of study drug.
• Brain metastases that are untreated or in the posterior fossa or involve the meninges. Participants with stable or previously treated progressing brain metastases (except in the posterior fossa or involving the meninges) may be permitted in a case-by-case basis at the Sponsor's discretion.
• Prolongation of corrected QT (QTc) interval to >470 millisecond (ms) for males and females when electrolytes balance is normal.
• Females who are breastfeeding or pregnant at screening or baseline
• Females of childbearing potential that refuse to use a highly effective method of contraception.
• Has uncontrolled or poorly controlled hypertension as defined by a sustained BP > 9. Has received prior investigational therapy within 5 half-lives of the agent or 4 weeks before the first administration of study drug, whichever is shorter.
• Has had any major cardiovascular event within 6 months prior to study drug 10. Has known hypersensitivity to any component in the formulation of ONM-501
• Has an active infection requiring systemic treatment
• Is participating in another therapeutic clinical trial Additional Exclusion Criteria for ONM-501 in Combination with cemiplimab (Part 1b)
• Has known hypersensitivity to any component in the formulation of cemiplimab
• Has any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (>10 mg daily prednisone equivalent)
• Has a condition requiring systemic treatment with corticosteroids
Drug: ONM-501, Drug: Cemiplimab
Multiple Myeloma, Bladder Cancer, Mycosis Fungoides, Metastatic Cancer, Lymphoma, Non-Hodgkin, Skin Cancer, Head and Neck Squamous Cell Carcinoma, Triple Negative Breast Cancer, Follicular Lymphoma, Mantle Cell Lymphoma, Diffuse Large B Cell Lymphoma, Carcinoma In Situ, Brain and Nervous System, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Kidney, Lung/Thoracic, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Skin, Rectum, Stomach, Urinary Bladder, Hodgkins Lymphoma, Kaposis sarcoma, Lymphoid Leukemia, Non-Hodgkins Lymphoma, Small Intestine, Soft Tissue, Tumor, Solid, Uveal Melanoma, Recurrent, Cervix Cancer, Tumor Recurrence
Solid tumors, Lymphoma, ONM-501, STING, Intra-tumoral, HNSCC, Breast Cancer, Melanoma, Skin Cancer, cemiplimab, Libtayo, DLBCL, bladder cancer, cervical cancer, metastases, immunotherapy, ICI, TNBC, Triple Negative, mTNBC, anti-PD-1 antibody, BRCA1, BRCA2, anti-PD-L1, uveal, NHL, Mantle Zone lymphoma, FL, stimulator of interferon genes
UT Southwestern
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder for Bladder Cancer Treatment, MODERN Study
This phase II/III trial examines whether patients who have undergone surgical removal of bladder, but require an additional treatment called immunotherapy to help prevent their bladder cancer from coming back, can be identified by a blood test. Many types of tumors tend to lose cells or release different types of cellular products including their DNA which is referred to as circulating tumor DNA (ctDNA) into the bloodstream before changes can be seen on scans. Health care providers can measure the level of ctDNA in blood or other bodily fluids to determine which patients are at higher risk for disease progression or relapse. In this study, a blood test is used to measure ctDNA and see if there is still cancer somewhere in the body after surgery and if giving a treatment will help eliminate the cancer. Immunotherapy with monoclonal antibodies, such as nivolumab and relatlimab, can help the body's immune system to attack the cancer, and can interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine if ctDNA measurement in blood can better identify patients that need additional treatment, if treatment with nivolumab prolongs patients' life and whether the additional immunotherapy treatment with relatlimab extends time without disease progression or prolongs life of bladder cancer patients who have undergone surgical removal of their bladder.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
206021
All
18 Years and over
Phase 3
NCT05987241
STU-2024-0089
Inclusion Criteria:
• PRE-REGISTRATION: Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. Variant histology, including neuroendocrine differentiation, is allowed if urothelial cancer is predominant histology (any amount of squamous differentiation is allowed provided the tumor is not a pure squamous cell cancer)
• PRE-REGISTRATION: Patient must have had radical cystectomy and lymph node dissection >= 3 weeks, but =< 12 weeks prior to pre-registration. Patients who have had a partial cystectomy as definitive therapy are not eligible
• PRE-REGISTRATION: No gross cancer at the surgical margins. Microscopic invasive urothelial carcinoma at the surgical margins (i.e., "positive margins") are allowed. Carcinoma in situ (CIS) at margins is considered negative margins
• PRE-REGISTRATION: No evidence of residual cancer or metastasis after cystectomy (imaging is not required prior to pre-registration but is required prior to registration)
• PRE-REGISTRATION: Have undergone a radical cystectomy with pathological evidence of urothelial carcinoma of the bladder at high risk of recurrence as described in one of the two scenarios below (i or ii). The 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized.:
• (i) Patients who have not received neoadjuvant cisplatin-based chemotherapy: pT3-pT4* or pT0/x-pT4/N+ on cystectomy and are not eligible for adjuvant cisplatin chemotherapy
• (i) Patients ineligible for cisplatin due to at least one of the following criteria and reason for ineligibility should be documented:
• (i) Creatinine Clearance (using Cockcroft-Gault): < 60 mL/min
• (i) Common Terminology Criteria for Adverse Events (CTCAE) version 5, grade >= 2 audiometric hearing loss
• (i) CTCAE version 5, grade >= 2 or above peripheral neuropathy
• New York Heart Association Class III heart failure
• (i) Eastern Cooperative Oncology Group (ECOG) performance status = 2
• (i) Patients who are eligible for cisplatin may be candidates if they refuse available adjuvant chemotherapy, despite being informed by the investigator about the treatment options. The patient's refusal must be documented.
• (i) Patients with pT2N0 urothelial cancer on cystectomy (without prior neoadjuvant chemotherapy) with ctDNA(+) Signatera results based on an assay performed post-cystectomy as part of routine care outside of the study may proceed with pre-registration but require confirmation of ctDNA(+) Signatera testing on repeat "central testing" in the context of A032103 testing. Patients with pT2N0 with central testing not confirming ctDNA(+) will not be eligible for A032103 (Note: this is distinct from patients with ypT2N0 who are eligible based on ii).
• (ii) Patients who received cisplatin-based neoadjuvant chemotherapy: ypT2-ypT4 or ypT0/x-pT4/N+ on cystectomy
• PRE-REGISTRATION: Available tumor tissue for central Signatera testing to be submitted after pre-registration. Central testing is defined as testing performed as part of the A032103 study prior to registration and is provided by the study and not routine standard commercial testing. Patients who have already had Signatera testing performed as part of routine care will require repeat central testing as part of the A032103 study to be eligible for registration/randomization. Tumor tissue from the cystectomy is preferred over tissue from prior transurethral resection
• PRE-REGISTRATION: Age >= 18 years
• PRE-REGISTRATION: ECOG Performance Status 0-2
• PRE-REGISTRATION: Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects
• PRE-REGISTRATION: No postoperative/adjuvant systemic therapy after cystectomy
• PRE-REGISTRATION: No adjuvant radiation after cystectomy
• PRE-REGISTRATION: No treatment with any other type of investigational agent =< 4 weeks before pre-registration
• PRE-REGISTRATION: Not have ever received prior treatment with PD-1/PD-L1 blockade.
• PRE-REGISTRATION: Not have ever received prior treatment with LAG-3 blockade.
• PRE-REGISTRATION: 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
• PRE-REGISTRATION: Absolute Neutrophil Count (ANC) >= 1,200/mm^3
• PRE-REGISTRATION: Platelet count >= 100,000/mm^3
• PRE-REGISTRATION: Hemoglobin >= 8 g/dL
• PRE-REGISTRATION: Creatinine =< 1.5 x upper limit of normal (ULN) or calculated (calc.) creatinine clearance > 30 mL/min (using either Cockcroft-Gault formula or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
• PRE-REGISTRATION: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x ULN
• PRE-REGISTRATION: Total bilirubin =< 1.5 x upper limit of normal (ULN) (except in patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
• PRE-REGISTRATION: For women of childbearing potential only: A negative urine or serum pregnancy test done =< 14 days prior to pre-registration is required
• PRE-REGISTRATION: Not currently requiring hemodialysis
• PRE-REGISTRATION: No current or prior history of myocarditis
• PRE-REGISTRATION: No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens- Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease.
• PRE-REGISTRATION: Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.
• PRE-REGISTRATION: Patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
• PRE-REGISTRATION: No current pneumonitis or prior history of non-infectious pneumonitis that required steroids within the previous 5 years.
• PRE-REGISTRATION: No known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected).
• PRE-REGISTRATION: 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.
• PRE-REGISTRATION: Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible.
• PRE-REGISTRATION: No concurrent antineoplastic therapy.
• PRE-REGISTRATION: No current immunosuppressive agents (with the exception of corticosteroids as described below).
• PRE-REGISTRATION: No condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of pre-registration (with the exception of steroid pre-medications for contrast allergies). Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• REGISTRATION: Patient must have had radical cystectomy and lymph node dissection =< 18 weeks prior to registration.
• REGISTRATION: Must have evaluable ctDNA Signatera assay result (i.e., ctDNA[+]or ctDNA[-]) based on test performed as part of central testing after pre-registration to A032103. Central testing is defined as testing performed as part of the A032103. Local/commercial testing results may not be used for registration to A032103
• Cisplatin-ineligible (or cisplatin-declining) patients with a pT2N0 urothelial cancer on cystectomy who were pre-registered based on routine standard care ctDNA(+) Signatera testing must have confirmed ctDNA(+) Signatera testing on central testing. If central Signatera testing yields a ctDNA(-) result, these patients are ineligible. NOTE: This is a distinct consideration from patients with ypT2-4 and/or ypN+ urothelial cancer (i.e., patients who had received neoadjuvant cisplatin-based chemotherapy) who are eligible with either ctDNA(+) or ctDNA(-) central Signatera testing
• REGISTRATION: All patients must have confirmed disease-free status defined as no measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or definitive non-measurable radiographic metastatic disease, within 60 days prior to registration. Patients with equivocal nodes less than 15 mm in short axis, or < 10 mm in long axis for non-lymph node lesions, not considered by the investigator to represent malignant disease will be eligible. Attempts should be made to resolve the etiology of equivocal lesions with complementary imaging (e.g., PET scan) or biopsy.
• REGISTRATION: No major surgery =< 3 weeks before registration.
• REGISTRATION: No live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette- Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist [registered trademark]) are live attenuated vaccines and are not allowed. Coronavirus disease 2019 (COVID-19) vaccines are not live vaccines and are allowed
• COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
• Patient must have converted to ctDNA(+) during serial monitoring performed centrally in the setting of the A032103 study
• COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
• No evidence of metastatic disease on the most recent scheduled imaging assessment as outlined in the study calendar (no repeat imaging is necessary specifically at the time of the conversion from ctDNA[-] to ctDNA[+]).
• COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
• No change in clinical condition and/or laboratory tests that would impact the safety of nivolumab in the opinion of the treating investigator
• COHORT B, ARM 4 PATIENTS INITIATING NIVOLUMAB AFTER CONVERSION OF ctDNA ASSAY FROM ctDNA(-) to ctDNA (+):
• =< 6 weeks from reporting of ctDNA(+) result by Natera.
Procedure: Biospecimen Collection, Other: cfDNA or ctDNA Measurement, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Biological: Nivolumab, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Biological: Relatlimab
Stage IV Bladder Urothelial Carcinoma AJCC v7, Stage II Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Muscle Invasive Bladder Urothelial Carcinoma
UT Southwestern
Study of PULSAR-ICI +/- IMSA101 in Patients With Oligoprogressive Solid Tumor Malignancies
Phase 2, open-label, multicenter, randomized study comparing the safety and efficacy of personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) combined with immune checkpoint inhibitor (ICI) immunotherapy (PULSAR-ICI) + IMSA101 and PULSAR-ICI alone in patients with oligoprogressive solid tumor malignancies after prior anti-cancer therapy.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Mona Arbab
212798
All
18 Years and over
Phase 2
NCT05846659
STU-2023-0837
Inclusion Criteria:
• Male or female patients ≥ 18 years of age
• Signed informed consent and mental capability to understand the informed consent
• Histologically or cytologically documented solid tumor malignancies demonstrating new progression through prior anti-cancer therapy, with a prior 2 months of clinical stability (with at least Stable Disease), with radiographically documented presence of ≤ 6 metastatic lesions consistent with the diagnosis of "oligoprogressive" disease that are technically amenable to PULSAR
• Patient's disease must be evaluable per RECIST Version 1.1
• All metastatic lesions amenable to administration of radiotherapy, at the discretion of the investigator
• Must have at least one single pre-defined progressing lesion/lesion site (longest diameter ≥ 10 mm and ≤ 50 mm) suitable for intra-tumoral injection
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
• Electrocardiogram (ECG) without evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the investigator
• Acceptable organ and marrow function as defined below:
• Absolute neutrophil count (ANC) > 1,500 cells/μL
• Platelets > 50,000 cells/μL
• Total bilirubin ≤ 1.5 times (×) the upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransaminase (ALT) ≤ 2.5 × ULN. If liver metastases are present, AST/ALT < 5 × ULN
• Serum creatinine < 1.5 mg/dL and a measured creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula
• Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 × ULN
• Women of child-bearing potential (defined as a female who has experienced menarche and who has not undergone successful surgical sterilization [hysterectomy, bilateral salpingectomy, or bilateral oophorectomy]) or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months with an appropriate clinical profile at the appropriate age, eg, greater than 45 years) must have a negative serum pregnancy test prior to first dose of study treatment
• Male and female patients with reproductive potential must agree to use two forms of highly effective contraception throughout the study
Exclusion Criteria:
• Prior receipt of stimulator of interferon genes (STING) agonist
• Prior receipt of therapeutic radiotherapy to all progressive lesions intended for PULSAR treatment
• Anti-cancer therapy, except pembrolizumab and nivolumab, within 4 weeks or < 5 half-lives of the first dose of study treatment
• Existence of primary tumor that requires therapeutic treatment beyond the provided immune checkpoint inhibitor drug
• Failure to recover, to Grade 1 or less, from clinically significant AEs due to prior anti-cancer therapy, as judged by the investigator
• Previous life-threatening (Grade 4) immune-related adverse event (irAE)
• Known untreated brain metastases or treated brain metastases that have not been stable (scan showing no worsening of central nervous system [CNS] lesion[s] and no requirement of corticosteroids) ≥ 4 weeks prior to study enrollment
• Existence of actionable mutations that are eligible for a mutation-targeting drug that represents standard-of-care
• Baseline prolongation of QT/corrected QT (QTc) interval (QTc interval > 470)
• 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
• Women who are pregnant or breastfeeding
• Sponsor reserves the right to exclude any patient from the study on the basis of pre-study medical histories, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria
Drug: IMSA101, Drug: Immune checkpoint inhibitor, Radiation: PULSAR
Other, Eye and Orbit, Anus, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Gall Bladder, Head and Neck, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Melanoma, skin, Ovary, Pancreas, Prostate, Rectum, Stomach, Throat, Thyroid, Urinary Bladder, Uterine (Endometrial), Vulva, Small Intestine, Unknown Sites, Oligoprogressive
Oligoprogressive solid tumor malignancies, Adult
UT Southwestern
Replacing Invasive Cystoscopy With Urine Testing for Non-muscle Invasive Bladder Cancer Surveillance (ReplaceCysto)
The purpose of this research is to determine whether bladder cancer monitoring can be improved by replacing some cystoscopy procedures with urine testing. Specifically, this study examines whether there are any differences in urinary symptoms, discomfort, number of invasive procedures, anxiety, complications, cancer recurrence or cancer progression when some cystoscopy procedures are replaced with urine testing.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
59883
All
18 Years and over
N/A
NCT05796375
STU-2023-0996
Inclusion Criteria:
• Aged 18 years or older
• History of low grade intermediate-risk non-muscle invasive bladder cancer, defined as most recent pathology report showing any of the following:
• multifocal low grade non-invasive urothelial carcinoma of any size
• solitary low grade non-invasive urothelial carcinoma greater than 3cm in size
• recurrent low grade non-invasive urothelial carcinoma
• Stated willingness to comply with all study procedures and availability for the duration of the study
• No evidence for recurrence at cystoscopy ≤4 months after most recent tumor resection
• Ability to consent in English or Spanish
Exclusion Criteria:
• History of total cystectomy of the bladder.
• History of urinary diversion (e.g., neo-bladder, colon pouch, or ileal conduit).
• History of muscle-invasive bladder tumor.
• Pregnancy or lactation.
• History of urothelial carcinoma of the ureter or renal pelvis status post endoscopic treatment or with evidence of recurrent upper tract disease (inclusion allowed if status post nephroureterectomy and recurrence free at time of inclusion)
• Anatomic constraints making cystoscopy impossible (e.g., history of urethrectomy, obliterated urethra secondary to stricture).
• Inability to provide a voided urine sample.
Procedure: Cystoscopy, Diagnostic Test: Bladder EpiCheck urine test, Diagnostic Test: Xpert Bladder Cancer Monitor urine test
Urinary Bladder, Non-muscle-invasive Bladder Cancer
Bladder, Cancer, Urology, Cystoscopy, Xpert, EpiCheck, Urine test
UT Southwestern
A Study of LSTA1 When Added to Standard of Care Versus Standard of Care Alone in Patients With Advanced Solid Tumors (BOLSTER)
The goal of this clinical trial is to test a new drug plus standard treatment compared with standard treatment alone in patients with advanced head and neck squamous cell carcinoma and cholangiocarcinoma. The main questions it aims to answer are: - is the new drug plus standard treatment safe and tolerable - is the new drug plus standard treatment more effective than standard treatment
Call 833-722-6237
canceranswerline@utsouthwestern.edu
David Hsieh
171069
All
18 Years and over
Phase 2
NCT05712356
STU-2023-0740
Inclusion Criteria:
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy ≥ 3 months
• At least one measurable metastatic lesion as assessed by RECIST 1.1
• Adequate organ and marrow function
• Adequate contraception
• Patients with any of the following:
• Histologically confirmed recurrent or metastatic HNSCC that is unresectable or considered incurable by local therapies and that has progressed after first-line immunotherapy. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Patients may not have primary tumor sites of the skin, paranasal sinuses, or the nasopharynx (any histology).
• Pathologically confirmed metastatic or unresectable cholangiocarcinoma or gallbladder carcinoma (GBC), with no prior systemic chemotherapy or targeted therapy or loco-regional therapy (including but not limited to transarterial chemoembolization, transarterial embolization, transarterial chemotherapy or transarterial radioembolization). Patients with recurrent disease more than 6 months after completion of adjuvant chemotherapy following curative resection are eligible.
Exclusion Criteria:
• Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, including but not limited to:
• Any major surgery or irradiation less than 4 weeks prior to baseline disease assessment
• Active infection (viral, fungal, or bacterial) requiring systemic therapy
• Known active hepatitis B virus, hepatitis C virus, or HIV infection
• Active tuberculosis as defined per local guidance
• History of allogeneic tissue/solid organ transplant
• Prior malignancy requiring active treatment within the previous 3 years 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
• Pregnant or breastfeeding
• Clinically significant or symptomatic cardiovascular/cerebrovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within 6 months before randomization
• History or clinical evidence of symptomatic central nervous system (CNS) metastases
• Has known allergies to taxanes or their standard pretreatments for unresectable or metastatic HNSCC
• For cholangiocarcinoma, active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with Type 1 diabetes, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
Drug: LSTA1, Drug: Paclitaxel, Drug: Durvalumab, Drug: Cisplatin, Drug: Gemcitabine, Drug: Placebo
Squamous Cell Carcinoma of the Larynx, Head and Neck Cancer, Cholangiocarcinoma, Head and Neck Squamous Cell Carcinoma, Gallbladder Cancer, Intrahepatic Cholangiocarcinoma, Bile Duct Cancer, Gallbladder Carcinoma, Esophagus, Lip, Oral Cavity and Pharynx, Other Digestive Organ, Squamous Cell Carcinoma of Head and Neck, HNSCC, Squamous Cell Carcinoma of the Head and Neck, Advanced Head and Neck Squamous Cell Carcinoma, Extrahepatic Cholangiocarcinoma, Cancer of the Head and Neck, Oropharynx Cancer, Oral Cavity Cancer, Hypopharynx Cancer, Larynx Cancer, Oral Cavity Squamous Cell Carcinoma, Squamous Cell Carcinoma of the Hypopharynx, Squamous Cell Carcinoma of the Oral Cavity, Squamous Cell Carcinoma of the Oropharynx, Gall Bladder Cancer, Gall Bladder Carcinoma, Oropharynx Squamous Cell Carcinoma, Hypopharynx Squamous Cell Carcinoma, Larynx Squamous Cell Carcinoma
immunotherapy, chemo, chemotherapy
UT Southwestern
A Study of STM-416 Administered to Patients Undergoing TURBT for Recurrent Bladder Cancer
This is a first-in-human (FIH), Phase 1/2a, multi center, open-label, single treatment, dose escalation and expansion study designed to determine the safety and tolerability of STM-416 in patients with bladder cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
59883
All
18 Years and over
Phase 1/Phase 2
NCT05710848
STU-2022-1032
Inclusion Criteria:
• Are aged 18 years or older;
• Have a history of pathologically confirmed high-grade Ta or T1 NMIBC without CIS who have completed SOC previously, with recurrent papillary disease seen on cystoscopy, and who are undergoing TURBT without perioperative intravesical chemotherapy;
• Are considered high risk for recurrence;
• Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2;
• Have adequate organ and marrow function as defined below:
• Hemoglobin 9.0 g/dL;
• Absolute neutrophil count 1.5 × 109/L (1500 per mm3);
• Platelet count 75 × 109/L (75,000 per mm3);
• Serum bilirubin 1.5 × institutional upper limit of normal (ULN);
• AST (serum glutamic-oxaloacetic transaminase)/ALT (serum glutamic-pyruvic transaminase) 2.5 × institutional ULN; and
• Creatinine CL 60 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine CL: Males: Creatinine CL (mL/min) = Weight (kg) × (140 - Age)/72 × serum creatinine (mg/dL); or Females: Creatinine CL (mL/min) = Weight (kg) × (140 - Age) × 0.85/72 × serum creatinine (mg/dL).
Exclusion Criteria:
• Have a history of CIS or MIBC;
• Are receiving any other investigational agents;
• Have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to resiquimod (R848), or excipients used in STM-416 including poloxamer 407 and sodium hyaluronate;
• Have an 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 would limit compliance with study requirements. Urinary tract infections are not exclusionary unless they are NCI-CTCAE Grade 3 or higher;
• Are a woman of childbearing potential regardless of contraceptive use; Note: Women of childbearing potential are only to be excluded in Phase 1 and Phase 2a to avoid bias due to the low prevalence of NMIBC in this population. However, they will be included in subsequent Phase 2/3 studies.
Drug: STM-416
Urinary Bladder, Non-muscle-invasive Bladder Cancer
Open-label, Dose escalation, STM-416, Resiquimod, Toll-like receptor 7/8, Non-Muscle Invasive Bladder Cancer, TURBT, Immunotherapy, BCG
UT Southwestern
Evaluating Safety and Biomarkers Using DK210 (EGFR) for Locally Advanced or Metastatic EGFR+ Tumors
This study will evaluate safety, pharmacodynamics and biomarkers of subcutaneous (SC) DK210(EGFR) given as monotherapy and in combination with immunotherapy, chemotherapy or radiation.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
177531
All
18 Years and over
Phase 1
NCT05704985
STU-2023-0521
Inclusion Criteria:
• ECOG performance status of 0-1
• Life expectancy of >3 months according to the investigator's judgment
• Solid tumors known for response on Il-2 or Il-10 and/or high expression of EGFR like all Non-small cell Lung, Skin, Head and Neck, Colon, Kidney, Bladder, Pancreatic cancers and all squamous cell carcinoma of other organs can be included with a classical histology report, specific EGFR expression or amplification reports are needed for other solid tumor types like gynecologic, prostate or triple negative breast cancer
• Measurable disease, defined as at least one (non-irradiated) lesion measurable on CT/MRI or bone scan as defined by RECIST 1.1.
• Progressive disease (PD) at study entry defined as one or more of the following criteria:
• Clinical PD with performance decline, clinical symptoms and/or observed tumor growth
• PD documented with imaging showing at least 20% growth (largest diameter) and/or new lesions
• Adequate cardiovascular, hematological, liver, and renal function.
• Subjects have failed one or more lines of systemic therapy and have not been operated on or receiving anti-cancer medication for at least 4 weeks.
• Males and females of childbearing potential must agree to use effective contraception starting prior to the first day of treatment and continuing during treatment
• Additional criteria may apply
Exclusion Criteria:
• Subjects with documented diffuse peritoneal disease or persistent abundant ascites
• Subjects with known prolonged QtC interval
• Concomitant or recent (<4 weeks or 5 half-lives of the last treatment, whichever is shorter) treatment with agents with anti-tumor activity, including immunotherapies, or experimental therapies. Bone treatments and supportive care can be continued
• Major surgery within 4 weeks, Radiation therapy for the treatment of metastases within less than 3 weeks (if single fraction of radiotherapy, then within 2 weeks) and radionuclide therapy for the treatment of metastases within 4 weeks prior to screening
• Uncontrolled intercurrent illness including, but not limited to, ongoing and uncontrolled infection (TBC, COVID or HIV patients treated with at least two anti-retroviral drugs and control of their infection with at least 500 /mm3 CD4+ T-cells in their blood and patients cured from Hepatitis B or C (i.e negativity of PCR) and liver function compatible with eligibility criteria are allowed to participate), multiple myeloma, multiple sclerosis, myasthenia gravis, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirement
• Any other conditions that, in the investigator's opinion, might indicate the subject to be unsuitable for the study
• Additional criteria may apply
Biological: DK210 (EGFR), Radiation: Radiation therapy, Biological: Immune checkpoint blockers, Drug: Chemotherapy
Kidney Cancer, Cancer, Colorectal Cancer, Head and Neck Cancer, Non Small Cell Lung Cancer, Gynecologic Cancer, Skin Cancer, Solid Tumor, Breast - Female, Breast - Male, Cervix, Colon, Kidney, Lung/Thoracic, Melanoma, skin, Other Urinary, Pancreas, Urinary Bladder, Pancreas Cancer
Cytokine, IL-2, Interleukin 2, IL-10, Interleukin 10, Oncology, Immuno-oncology, DK210(EGFR), Immunotherapy, DEKA, DEKA Biosciences
UT Southwestern
A Study of LOXO-435 in Participants With Cancer With a Change in a Gene Called FGFR3
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435. LOXO-435 may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Participation could last up to 30 months (2.5 years) and possibly longer if the disease does not get worse.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
206021
All
18 Years and over
Phase 1
NCT05614739
STU-2023-0080
Inclusion Criteria:
• Have solid tumor cancer with an FGFR3 pathway alteration on molecular testing in tumor or blood sample that is deemed as actionable.
• Cohort A1 (Dose Escalation): Presence of an alteration in FGFR3 or its ligands.
• Cohort A2 (Dose Optimization): Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 alteration.
• Cohorts B1, B2 and B3 (Dose Expansion): Histological diagnosis of urothelial cancer that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
• Cohort C (Dose Expansion): Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a prespecified activating FGFR3 alteration.
• Measurability of disease:
• Cohort A1: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
• Cohorts A2, B1, B2, B3, and C1: Measurable disease required as defined by RECIST v1.1
• Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country-specific regulations.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Prior Systemic Therapy Criteria:
• Cohort A1/C1: Participant has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating Investigator; OR the participant is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies.
• Cohort A2/B1/B2/B3: Participants must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
• FGFR inhibitor specific requirements:
• Cohort A1/A2: Prior FGFR inhibitor treatment is permitted, but not required.
• Cohort B1: Participants must have been previously treated with a FGFR inhibitor.
• Cohort B2, B3, C1: Participants must be FGFR inhibitor naïve.
Exclusion Criteria:
• Participants with primary central nervous system (CNS) malignancy.
• Known or suspected history of uncontrolled CNS metastases.
• Current evidence of corneal keratopathy or retinal disorder.
• Have a history and/or current evidence of extensive tissue calcification.
• Any serious unresolved toxicities from prior therapy.
• Significant cardiovascular disease.
• Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF).
• Active uncontrolled systemic infection or other clinically significant medical conditions.
• Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled.
Drug: LOXO-435, Drug: Pembrolizumab
Neoplasm Metastasis, Urinary Bladder Neoplasms, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, 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, Kaposis sarcoma, Small Intestine, Soft Tissue, Unknown Sites, Ureteral Neoplasms
Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer, Ureter Cancer
UT Southwestern; Parkland Health & Hospital System
A Study of Evorpacept (ALX148) With Enfortumab Vedotin for Subjects With Urothelial Carcinoma (ASPEN-07)
AT148007 is a Phase 1, open-label, multicenter, safety, pharmacokinetic, pharmacodynamic study of ALX148 in combination with enfortumab vedotin and/or other anticancer therapies in subjects with urothelial carcinoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
206021
All
18 Years and over
Phase 1
NCT05524545
STU-2022-1097
Inclusion Criteria:
• Histologically confirmed, unresectable locally advanced or metastatic urothelial carcinoma.
• Must have received prior treatment with an immune checkpoint inhibitor (CPI).
• Subjects must have received prior treatment with platinum-containing chemotherapy.
• Subjects must have had progression or recurrence of urothelial cancer.
• Subjects must have measurable disease according to RECIST (Version 1.1).
• Adequate bone marrow function.
• Adequate renal function.
• Adequate liver function.
• Adequate Eastern Cooperative Oncology Group (ECOG) performance status.
Exclusion Criteria:
• Preexisting sensory or motor neuropathy Grade ≥2.
• Presence of symptomatic or uncontrolled central nervous system (CNS) metastases.
• Prior treatment with enfortumab vedotin or other monomethylauristatin (MMAE)-based antibody-drug conjugate (ADCs)
• Prior treatment with any anti-CD47 or anti-signal regulatory protein-α (SIRPα) agent.
• Known active keratitis or corneal ulcerations. Subjects with superficial punctate keratitis are allowed if the disorder is being adequately treated.
• History of uncontrolled diabetes mellitus within 3 months of the first dose of study drug.
Drug: Evorpacept, Drug: Enfortumab Vedotin
Bladder Cancer, Urothelial Carcinoma, Urinary Bladder
UT Southwestern
Reduced-dose Botox for Urgency Incontinence Among Elder Females (RELIEF)
The purpose of this study is to study the treatment of urgency urinary incontinence (UUI), specifically among women 70 years and older, by comparing reduced versus standard dose of onabotulinumtoxinA (BTX; trade name BOTOX(c)) injection in the bladder.
Call 214-648-5005
studyfinder@utsouthwestern.edu, JOSE.SANTOYO@UTSouthwestern.edu
Ramy Goueli
189632
Female
70 Years and over
Phase 1/Phase 2
NCT05512039
STU-2022-0938
Inclusion Criteria:
• Adult female at least 70 years old at date of enrollment
• Urge-predominant mixed urinary incontinence (urge>stress per the MESA questionnaire)
• On average 2 or more urgency or insensible incontinence episodes per day per patient report
• Refractory urinary urgency incontinence, defined as
• Persistent symptoms despite trial of one or more conservative treatments (e.g. behavioral therapy, physical therapy, home Kegel exercises); participants not required to have attempted first line therapies if deemed not feasible or appropriate by provider with input of participant/caregiver.
• Persistent symptoms despite the use of anticholinergic and/or beta-3 agonist medication; or inability to tolerate medication due to side effects, or has a contraindication to taking medication, or is unable to afford the cost of the medication.
• Currently not on an anticholinergic or beta-3 agonist medication or is willing to stop medication for 3 weeks prior to completing baseline bladder tally, with plan to remain off medication through duration of the study. Currently not actively using sacral neuromodulation therapy (either has not tried, or unit has been off for 4 weeks prior to baseline bladder tally and will remain turned off for the duration of the study). It is permissible for participants to continue self-led conservative therapies during participation in the study, including Kegel exercises, avoidance of bladder irritants, and urge suppression.
• Willing and able to complete all study-related items, with assistance of caregiver(s) if needed.
• Demonstrates awareness of possible need for catheterization in event of post-injection urinary retention & acknowledges risks of catheterization. Participant does not need to demonstrate ability to perform self-catheterization.
• Grossly neurologically normal on exam and no gross systemic neurologic conditions believed to affect urinary function. Patients with a diagnosis of Parkinson's disease or diabetes may be eligible provided they have a grossly normal neurologic exam and otherwise fulfill the inclusion/exclusion criteria.
Exclusion Criteria:
• Lack of capacity to provide consent. Will be assessed if needed per judgment of the site PI and study staff, with use of optional questionnaire.
• Baseline persistently elevated post-void residual [PVR] (>150mL on 2 occasions in the 6 weeks prior to enrollment). If the PVR was obtained via bladder scanner with measurements differing by more than 100mL, or if there is concern about the accuracy of the scanner, it will be confirmed via catheterization which will be considered the gold standard.
• Need for BTX injection to take place in the Operating Room or under sedation. (Of note, for repeat injection under the protocol, patients may have OR injection if indicated due to pain with initial BTX injection.)
• Previous treatment with intravesical BTX in the last 12 months or use of sacral neuromodulation therapy within the past 4 weeks (unit may remain implanted, but should remain off for duration of the study).
• Untreated symptomatic urinary tract infection (UTI). Eligible once UTI treatment complete and symptoms resolved.
• Known bladder abnormality, including current or prior bladder malignancy, carcinoma in situ or untreatable cystitis (e.g. eosinophilic cystitis); prior major bladder surgery that would alter the detrusor muscle, such as augmentation cystoplasty; or hematuria that has not been evaluated.
• Neurogenic detrusor overactivity or neurologic disease that may impact bladder function, including stroke, multiple sclerosis, peripheral neuropathy, spinal cord injury. Conditions such as Parkinson's disease and diabetes are acceptable provided normal bladder emptying and grossly normal neurologic function.
• Concurrent BTX use for other indication, participants cannot exceed 300 units BTX in a 3 month period. Participants who may have conflict between study BTX administration and administration for other purposes may be excluded from participation if there is concern that study drug administration will be compromised. Concurrent use of BTX for another indication that would not exceed 300 units in a 3 month period, or that can have time of administration of the other BTX adjusted to avoid excessive dose, is acceptable; for instance, for migraines.
• Greater than stage 2 pelvic floor prolapse, uncorrected or persistent despite pessary use (leading edge of prolapse not greater than 1cm beyond the hymen). Ongoing pessary use is permissible. Patients may have had a prior repair for pelvic organ prolapse. (see chart review of recent exam or perform brief exam while collecting post-void residual)
• Planned prolapse or stress incontinence surgery; would defer enrollment to >3 months post-operative.
• Allergy or intolerance to lidocaine or BTX.
• Participation in another research study that could conflict with the RELIEF study, in estimation of the site PI.
Drug: Botox 50 Unit Injection, Drug: Botox 100 Unit Injection
Overactive Bladder, Urinary Bladder, Urinary Incontinence in Old Age, Urgency Urinary Incontinence
Urinary Incontinence, Urgency Urinary Incontinence, Overactive Bladder
UT Southwestern; Parkland Health & Hospital System
A Study to Evaluate Safety, Efficacy of FF-10832 in Combination With Pembrolizumab in Solid Tumors
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 solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
John Lohrey
161945
All
18 Years and over
Phase 2
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. I
• 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 Solid Tumor, Lung/Thoracic, Urinary Bladder
UT Southwestern
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
206021
All
18 Years and over
Phase 2
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
• 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
169573
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
Study of BOTOX Injections to Assess Change in Disease Activity and Adverse Events in Adult Female Participants With Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)
Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic and debilitating urological complex of disorders characterized by symptoms of bladder pain or discomfort, mostly upon bladder filling, and often accompanied by lower urinary tract symptoms (LUTS). This study will assess how safe and effective BOTOX (onabotulinumtoxinA) is in treating IC/BPS. Adverse events and change in disease symptoms will be evaluated. BOTOX (onabotulinumtoxinA) is an investigational drug being developed for the treatment of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). Study doctors randomly assign the participants to 1 of 2 groups, called treatment arms, to receive BOTOX or placebo. There is a 1 in 2 chance that participants will be assigned to placebo. Approximately 80 female participants, aged 18 to 75 years, with a diagnosis of IC/BPS will be enrolled in approximately 40 sites in the United States and Canada. Participants will receive BOTOX or placebo injected into the bladder on Day 1 and will be followed for at least 12 weeks in treatment 1. Eligible participants may request additional dose of BOTOX between Weeks 12 and 24, and will be followed for 12 weeks in treatment period 2. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
Call 214-648-5005
studyfinder@utsouthwestern.edu, AGNES.BURRIS@UTSouthwestern.edu
Maria Florian-Rodriguez
164281
Female
18 Years to 75 Years old
Phase 2
NCT05141006
STU-2022-0422
Inclusion Criteria:
• Presence of Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) symptoms for at least 6 months, diagnosed by the investigator as IC/BPS, and confirmed dominant bladder derived pain.
Exclusion Criteria:
• History or current diagnosis of Hunner Lesions.
Drug: BOTOX, Drug: Placebo for BOTOX
Urinary Bladder, Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS)
Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS), BOTOX, Botulinum Toxin Type A, OnabotulinumtoxinA
UT Southwestern
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
59883
All
18 Years and over
Phase 1
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, Non-muscle Invasive Bladder Cancer, Carcinoma Transitional Cell, NMIBC
Bladder Cancer, Urothelial Cancer, Enfortumab vedotin, PADCEV, Pharmacokinetics
UT Southwestern
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
183526
All
18 Years and over
Phase 1
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]) =<
• 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: Computed Tomography, Drug: Enfortumab Vedotin, Drug: Erdafitinib
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, 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
193600
All
18 Years and over
Phase 3
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
Immunotherapy With or Without Radiation Therapy for Metastatic Urothelial Cancer
This phase II trial compares the effect of adding radiation therapy to an immunotherapy drug called pembrolizumab versus pembrolizumab alone in treating patients with urothelial cancer that has spread from where it first started (primary site) to other places in the body (metastatic). The addition of radiation to immunotherapy may shrink the cancer, but it could also cause side effects. Immunotherapy with monoclonal antibodies such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that uses high energy x-rays to kill tumor cells and shrink tumors. This method uses special equipment to position a patient and precisely deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and may cause less damage to normal tissue than conventional radiation therapy. The combination of pembrolizumab and radiation therapy may be more efficient in killing tumor cells.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
42296
All
18 Years and over
Phase 2
NCT04936230
STU-2024-0032
Inclusion Criteria:
• Histologically confirmed metastatic urothelial carcinoma
• Patients must be either ineligible for platinum treatment or platinum refractory as defined below:
• Platinum-ineligible: If patients meet any one of the following criteria:
• Impaired renal function (creatinine clearance [CrCl] of < 30 mL/min)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of > 2
• Grade > 2 peripheral neuropathy
• New York Heart Association (NYHA) Heart Failure of > 3
• Platinum-refractory: If patients meet any one of the following criteria:
• Prior platinum-based perioperative chemotherapy within 12 months of relapse
• Prior platinum-based chemotherapy for metastatic disease
• Patients must have at least one measurable site >= 1 cm in diameter per RECIST 1.1 and a site targetable for radiotherapy. Measurable site must not overlap with radiated site such that measurable site cannot receive > 2 Gy per fraction
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions)
• Men and women, ages >= 18 years of age
• ECOG performance status =< 2
• Leukocytes >= 2,500/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin >= 8 g/dL
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be enrolled)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x upper limit of normal (ULN)
• AST and/or ALT =< 5 x ULN for patients with liver involvement
• Alkaline phosphatase =< 2.5 x ULN
• =< 5 x ULN for patients with documented liver involvement or if due to bone metastases primarily in absence of liver disease, no limitation
• No prior allogeneic bone marrow transplantation or prior solid organ transplantation
• No prior radiotherapy to targetable site or measurable site
• No chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier. However, the following therapies are allowed:
• Hormone-replacement therapy or oral contraceptives
• Palliative radiotherapy for bone metastases > 2 weeks prior to registration
• No prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• No treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• No prior treatment with any other investigational agent within 4 weeks prior to registration
• No prior treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to registration
• Any prior systemic therapy is permitted except therapy with PD1/PDL1 inhibitor
• Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
• No active tuberculosis (TB)
• No known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Patients with known primary central nervous system (CNS) malignancy or symptomatic CNS metastases are excluded, with the following exceptions:
• Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
• Evaluable or measurable disease outside the CNS
• No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
• No history of intracranial hemorrhage or spinal cord hemorrhage
• No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted
• No neurosurgical resection or brain biopsy within 28 days prior to registration
• Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
• Radiographic demonstration of improvement upon the completion of CNS directed therapy and no evidence of interim progression between the completion of CNS directed therapy and the screening radiographic study
• No stereotactic radiation or whole-brain radiation within 28 days prior to registration
• Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
• No 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 (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible
• No known history of, or any evidence of active, non-infectious pneumonitis or colitis
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• No known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; or inherited liver disease causing decompensated cirrhosis
• No history of idiopathic pulmonary fibrosis, pneumonitis (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. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• No significant cardiovascular disease (such as New York Heart Association class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
• No other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
• No history of leptomeningeal disease
• No uncontrolled tumor-related pain
• Patients requiring pain medication must be on a stable regimen at study entry
• Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period
• Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment
• No uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Patients with indwelling catheters (e.g., PleurX [registered trademark]) are allowed
• Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are eligible
• 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:
• Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
• 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
• 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)
• No 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 would limit compliance with study requirements
• No active infections requiring systemic antibiotics within 2 weeks prior to registration. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
• No major surgical procedure within 28 days prior to registration or anticipation of need for a major surgical procedure during the course of the study
• No administration of a live, attenuated vaccine within 30 days before registration or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of immunotherapy
• Patients who have received live attenuated vaccines within 30 days of the first dose of trial treatment are eligible at the discretion of the investigator. All seasonal influenza vaccines and vaccines intended to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) are allowed
• Physicians should consider whether any of the following may render the patient inappropriate for this protocol:
• Patients with life expectancy of less than 6 months
• Psychiatric illness which would prevent the patient from giving informed consent
• Medical conditions such as uncontrolled infection, uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
• 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 a "currently active" second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for >= 3 years
• Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study and for 4 months (120 days) after the last dose of study agent 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). 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
• 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)
Procedure: Biospecimen Collection, Procedure: Bone Scan, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Biological: Pembrolizumab, Procedure: Positron Emission Tomography, Other: Questionnaire Administration, Radiation: Stereotactic Body Radiation Therapy
Metastatic Urothelial Carcinoma, Stage IV Bladder Cancer AJCC v8, Urinary Bladder, Platinum-Resistant Urothelial Carcinoma
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
59883
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
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
59883
All
18 Years and over
Phase 1/Phase 2
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 effective double-barrier contraception 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).
• 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
Contrast Ultrasound for Pediatric Trauma - Comparative Evaluation (CAPTURE Study)
This multicenter study aims to evaluate the accuracy of contrast-enhanced ultrasound (CEUS) in diagnosing abdominal solid organ injuries in pediatric patients. Up to 130 subjects will complete the study across approximately 5-10 sites in the US, with up to 30 patients in the training phase (3 per site) and 100 patients in the treatment phase of the study. All subjects will have had a CT scan as part of standard of care, confirming at least one solid organ abdominal injury. The study procedure will occur within 48 hours from time of injury. All subjects will have an abdominal ultrasound without contrast, followed by a contrast-enhanced ultrasound using the contrast agent Lumason. Ultrasound and contrast-enhanced ultrasound results will be compared to the CT scan results. The CT and ultrasound scans will be read locally and will undergo central review.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Michael.Fulkerson@UTSouthwestern.edu
Jeannie Kwon
83212
All
8 Years to 18 Years old
Phase 1/Phase 2
NCT04718441
STU-2020-1359
Inclusion Criteria:
• Hemodynamically stable, as determined by the trauma team
• Age 8 through 18 years (inclusive)
• Interpretable CT of the abdomen and pelvis that demonstrates at least one solid organ injury among the liver, spleen, pancreas, and kidneys
• Plan for observation or admission to the hospital
• Candidate for abdominal ultrasound based on body habitus, as determined by the investigator
• Glasgow Coma Score of 15
• Able to complete the study procedures within 48 hours of injury
Exclusion Criteria:
• Known cardiac abnormality
• Pulmonary Hypertension
• Known sensitivity to any Lumason components - including sulfur hexafluoride, polyethylene glycol 4000, distearoylphosphatidylcholine (DSPC), dipalmitoylphosphatidylglycerol sodium (DPPG-Na), or palmitic acid
• Unable to be rolled onto side to allow lateral ultrasound windows if necessary
• Unable to assent or consent
• Pregnant
• Lactating
• CT images not available for transmission to central image repository
Drug: Lumason
Cardiovascular, Gall Bladder, Kidney, Liver, Pancreas, Soft Tissue, Abdominal Injury
Solid Organ Injury
Children’s Health
A Study of TAR-200 in Combination With Cetrelimab, TAR-200 Alone, or Cetrelimab Alone in Participants With Non-Muscle Invasive Bladder Cancer (NMIBC) Unresponsive to Intravesical Bacillus Calmette-Guérin Who Are Ineligible for or Elected Not to Undergo Radical Cystectomy (SunRISe-1)
The purpose of this study is to evaluate the overall complete response (CR) rate in participants treated with TAR-200 in combination with cetrelimab (Cohort 1), or TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3) with Carcinoma in Situ (CIS), with or without concomitant high-grade Ta or T1 papillary disease; and disease-free survival (DFS) in participants treated with TAR-200 alone with papillary disease only (Cohort 4).
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Yair Lotan
59883
All
18 Years and over
Phase 2
NCT04640623
STU-2021-0452
Inclusion Criteria:
• Histologically confirmed diagnosis of persistent or recurrent high-risk non-muscle invasive bladder cancer (HR-NMIBC), (carcinoma in situ [CIS] or tumor in situ [Tis]), with or without papillary disease (T1, high-grade Ta) or papillary disease only (high-grade Ta or any T1 and absence of CIS), within 12 months of completion of the last dose of Bacillus Calmette-Guerin (BCG) therapy, in participants who have received adequate BCG. Mixed histology tumors are allowed if urothelial differentiation (transitional cell histology) is predominant. However, the presence of neuroendocrine, micropapillary, signet ring cell, plasmacytoid, or sarcomatoid features will make a participant ineligible. For participants with lamina propria invasion (T1) on the screening biopsy/ transurethral resection of bladder tumor (TURBT), muscularis propria must be present in order to rule out Muscle Invasive Bladder Cancer (MIBC)
• All visible papillary disease must be fully resected (absent) prior to randomization (residual CIS is acceptable for participants eligible for Cohorts 1, 2, and 3 only) and documented in the electronic case report form (eCRF) at screening cystoscopy. For participants with papillary disease only (Cohort 4), local urine cytology at screening must be negative or atypical (for High-Grade Urothelial Carcinoma [HGUC])
• Participants must be ineligible for or have elected not to undergo radical cystectomy
• BCG-unresponsive high-risk NMIBC after treatment with adequate BCG therapy defined as a minimum of 5 of 6 full doses of an induction course (adequate induction) plus 2 of 3 doses of a maintenance course, or at least 2 of 6 doses of a second induction course
• Eastern Cooperative Oncology Group (ECOG) performance status Grade 0, 1, or 2
Exclusion Criteria:
• Presence or history of histologically confirmed, muscle-invasive, locally advanced, nonresectable, or metastatic urothelial carcinoma (that is, T2, T3, T4, and/or Stage IV)
• Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder. Ta/T1/CIS of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to randomization
• Received a live virus vaccine within 30 days prior to the initiation of study treatment. Inactivated (non-live or non-replicating) vaccines approved or authorized for emergency use (for example, COVID-19) by local health authorities are allowed
• Active hepatitis B or C infection (for example, participants with history of hepatitis C infection but undetectable hepatitis C virus polymerase chain reaction (PCR) test and participants with history of hepatitis B infection with positive hepatitis B surface antigen (HBsAg) antibody and undetectable PCR are allowed)
• Prior therapy with an anti-programmed-cell death 1 (PD-1), anti-PD-ligand 2 (L2) agent, or with an agent directed to another co-inhibitory T-cell receptor
Drug: TAR-200, Biological: Cetrelimab
Urinary Bladder Neoplasms, Urinary Bladder
UT Southwestern
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
42296
All
18 Years and over
Phase 3
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
• 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, 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
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
128737
All
up to 25 Years old
Phase 1/Phase 2
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
• 9. Life expectancy greater than or equal to 12 weeks, in the investigator's opinion.
• Adequate hematologic, renal and hepatic function. Phase 2
• Cohort Specific
• 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.
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
• 9. 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 Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that that has spread from where it first started (primary site) to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
42296
All
18 Years and over
Phase 2
NCT03866382
STU-2019-1012
Inclusion Criteria:
• Metastatic disease defined as new or progressive lesions on cross-sectional imaging or bone scan. Patients must have at least:
• One measurable site of disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
• One bone lesion on bone scan (tec99 or sodium fluoride [NaF] PET/CT, CT or MRI) for the bone-only cohort.
• Histologically confirmed diagnosis of one of the following metastatic cohorts:
• Small cell/ neuroendocrine carcinoma of the bladder- All urothelial carcinomas with any amount of neuroendocrine differentiation (including small cell differentiation) will be included. If the tumor is purely neuroendocrine, metastasis from another site of origin should be clinically excluded
• Adenocarcinoma of the bladder, or urachal adenocarcinoma, or bladder/urethra clear cell adenocarcinoma - must be pure (per World Health Organization [WHO] definition), (i.e. urothelial carcinoma with glandular differentiation is not considered a pure adenocarcinoma
• Squamous cell carcinoma of the bladder - must be pure (i.e. urothelial carcinoma with squamous differentiation is not considered a pure squamous cell carcinoma)
• Plasmacytoid urothelial carcinoma - Tumor should show predominantly > or equal ~ 50% plasmacytoid histology (including all types of discohesive growth, such as tumors with signet-ring and/or rhabdoid features as well)
• Any penile cancer
• Sarcomatoid renal cell carcinoma - Tumor should be predominantly sarcomatoid ~ 50% (including rhabdoid differentiation) is also unclassified renal cell carcinomas (RCCs): all (assuming they are high grade with metastasis) malignant angiomyolipomas are allowed
• Sarcomatoid urothelial carcinoma - Tumor should show predominantly ~ 50% sarcomatoid differentiation
• Renal medullary carcinoma - Per WHO definition, ideally confirmed with immunostains
• Renal collecting duct carcinoma - Per WHO definition (medullary involvement, predominant tubular morphology, desmoplastic stromal reaction, high grade cytology, infiltrative growth pattern, and absence of other renal cell carcinoma subtype or urothelial carcinoma)
• Bone only urothelial carcinoma or other non-prostate GU tumor
• Urethra carcinoma- May be of any histology but if urothelial carcinoma then must be isolated to the urethra and not have metachronous or synchronous urothelial carcinoma of the bladder
• Other miscellaneous histologic variants of the urothelial carcinoma, such as, but not limited to : micropapillary (Tumor should show predominantly > or equal 50% micropapillary architecture), giant cell, lipid-rich, clear cell and nested variants (Tumor should predominantly > or equal 50% show these features), large cell neuroendocrine carcinoma, lymphoepithelioma-like carcinoma and mixed patterns will be considered, as well as small cell neuroendocrine prostate cancer (Only treatment-naïve primary small cell of prostate with any amount of small cell component allowed. Post-treatment small cell prostatic carcinomas are not allowed), Malignant testicular Sertoli or Leydig cell tumors, and papillary and chromophobe RCC
• Note: Translocation positive renal cell carcinoma patients are eligible. However, AREN1721 should be considered before this trial
• Hematoxylin and eosin (H&E) slides from diagnostic tumor tissue for retrospective central pathology review
• Patients may have received up to 2 systemic anti-cancer treatments or be treatment naive. Patients with small cell carcinoma should have received a platinum-based combination regimen either as neoadjuvant, adjuvant or first-line treatment). Patients in the bone-only cohort may be urothelial carcinoma histology but must receive standard cisplatin-based chemotherapy (if cisplatin-eligible)
• Age >= 18 years
• Patients must be able to swallow oral formulation of the tablets
• Karnofsky performance status >= 80%
• Absolute neutrophil count (ANC) >= 1,000/mcL
• Platelet count >= 75,000/mcL
• Total bilirubin =< 1.5 x upper limit of normal (ULN). For subjects with known Gilbert's disease or similar syndrome with slow conjugation of bilirubin, total bilirubin =< 3.0 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (ULN) (or =< 5 x ULN for patients with liver metastases or Gilbert's disease)
• Creatinine =< 1.5 x upper limit of normal (ULN) OR creatinine clearance >= 40 mL/min/1.73 m^2 (calculated using the Chronic Kidney Disease Epidemiology [CKD-EPI] equation or Cockcroft-Gault formula) for patients with creatinine levels above institutional normal
• Hemoglobin >= 9 g/dL (transfusion of packed red blood cells [PRBCs] allowed)
• Serum albumin >= 3.2 g/dL
• Lipase and amylase =< 2.0 x ULN and no radiologic (on baseline anatomical imaging) or clinical evidence of pancreatitis
• Prior treatment with MET or VEGFR inhibitors is allowed. However, prior cabozantinib will not be allowed. Also, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are also not allowed
• Prior treatment with any therapy on the PD-1/PD-L1 axis or anti- CTLA-4/CTLA-4 inhibitors is allowed, either in the perioperative or in the metastatic setting. However, patients that have received both prior MET or VEGF and prior PD-1/PD-L1/CTLA-4 (sequentially or in combination) are not allowed
• Human immunodeficiency virus (HIV)-positive patients are eligible if on stable dose of highly active antiretroviral therapy (HAART), no clinically significant drug-drug interactions are anticipated with the current HAART regimen, CD4 counts are greater than 350 and viral load is undetectable
• Patients with rheumatoid arthritis and other rheumatologic arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication only and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies etc. are eligible but should be considered for rheumatologic evaluation for the presence of target organ involvement and potential need for systemic treatment
• Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones or medications (e.g. thyroiditis managed with propylthiouracil [PTU] or methimazole) including physiologic oral corticosteroids are eligible
• Patients who have evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction, within 12 months are not eligible
• Women of childbearing potential must have a negative pregnancy test =< 7 days prior to registration
• Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Post menopause is defined as amenorrhea >= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason
• Pregnant women may not participate in this study because with cabozantinib, nivolumab, and ipilimumab have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cabozantinib, nivolumab, and ipilimumab, breastfeeding should be discontinued if the mother is treated with these agents
• The patient has received no cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 2 weeks before the first dose of study treatment
• The patient has received no radiation therapy:
• To the lungs and mediastinum or abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
• To brain metastasis within 3 weeks for whole-brain radiotherapy (WBXRT), and 2 weeks for stereotactic body radiation therapy (SBRT) before the first dose of study treatment
• To the abdomen within 4 weeks before the first dose of study treatment, or has ongoing complications, or is healing from prior radiation therapy
• To any other site(s) within 2 weeks before the first dose of study treatment
• The patient has received no radionuclide treatment within 6 weeks of the first dose of study treatment
• The patient has received no prior treatment with a small molecule kinase inhibitor within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment
• The patient has received no prior treatment with hormonal therapy within 14 days or five half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment. Subjects receiving gonadotropin-releasing hormone (GnRH) agonists and antagonists are allowed to participate
• The patient has not received any other type of investigational agent within 14 days before the first dose of study treatment
• The patient must have recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except alopecia, neuropathy and other non-clinically significant adverse events (AEs) defined as lab elevation with no associated symptoms or sequelae
• The patient may not have active brain metastases or epidural disease. Patients with brain metastases previously treated with whole brain radiation or radiosurgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible. Neurosurgical resection of brain metastases or brain biopsy is permitted if completed at least 3 months before starting study treatment. Baseline brain imaging with contrast-enhanced CT or MRI scans for subjects with known brain metastases is required to confirm eligibility
• No concomitant treatment with warfarin. Aspirin (up to 325 mg/day), thrombin or factor Xa inhibitors, low-dose warfarin (=< 1 mg/day), prophylactic and therapeutic low molecular weight heparin (LMWH) are permitted
• No chronic concomitant treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's wort) or strong CYP3A4 inhibitors
• Because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information. 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
• The patient has not experienced any of the following:
• Clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment
• Hemoptysis of >= 0.5 teaspoon (2.5 mL) of red blood per day within 1 months before the first dose of study treatment
• Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
• The patient has no tumor invading any major blood vessels
• The patient has no evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib. Patients with rectal tumor masses are not eligible
• The patient has no uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders including:
• Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening.
• Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
• The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before randomization. Note: if initial QTcF is found to be > 500 ms, two additional electrocardiograms (EKGs) separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is =< 500 ms, the subject meets eligibility in this regard
• Any history of congenital long QT syndrome
• Any of the following within 6 months before registration of study treatment:
• Unstable angina pectoris
• Clinically-significant cardiac arrhythmias (patients with atrial fibrillation are eligible)
• Stroke (including transient ischemic attack [TIA], or other ischemic event)
• Myocardial infarction
• Cardiomyopathy
• No significant gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
• Any of the following that have not resolved within 28 days before the first dose of study treatment:
• Active peptic ulcer disease
• Acute diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or malabsorption syndrome
• None of the following within 2 years before the first dose of study treatment:
• Abdominal fistula or genitourinary fistula
• Gastrointestinal perforation
• Bowel obstruction or gastric outlet obstruction
• Intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than 2 years before the first dose of study treatment
• Disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement are not eligible
• No other clinically significant disorders such as:
• Severe active infection requiring IV systemic treatment within 14 days before the first dose of study treatment
• Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
• History of organ or allogeneic stem cell transplant
• Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment (for asymptomatic patients with an elevated thyroid-stimulating hormone [TSH], thyroid replacement may be initiated if clinically indicated without delaying the start of study treatment)
• No history of major surgery as follows:
• Major surgery within 3 months of the first dose of cabozantinib; however, if there were no wound healing complications, patients with rapidly growing aggressive cancers, may start as soon as 6 weeks if wound has completely healed post-surgery
• Minor surgery within 1 month of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications excluding core biopsies and mediport placement
• Complete wound healing from prior surgery must be confirmed before the first dose of cabozantinib irrespective of the time from surgery
• No history of severe hypersensitivity reaction to any monoclonal antibody
• No evidence of active malignancy, requiring systemic treatment within 2 years of registration
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cabozantinib, nivolumab, ipilimumab or other agents used in study
• No positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. If HBV sAG is positive, subsequent ribonucleic acid (RNA) polymerase chain reaction (PCR) must be negative
• No patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include, but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
Procedure: Bone Scan, Drug: Cabozantinib S-malate, Procedure: Computed Tomography, Biological: Ipilimumab, Procedure: Magnetic Resonance Imaging, Biological: Nivolumab, Procedure: Positron Emission Tomography
Bladder Adenocarcinoma, Papillary Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Bladder Mixed Adenocarcinoma, Bladder Squamous Cell Carcinoma, Chromophobe Renal Cell Carcinoma, Kidney Medullary Carcinoma, Large Cell Neuroendocrine Carcinoma, Metastatic Bladder Carcinoma, Metastatic Bladder Large Cell Neuroendocrine Carcinoma, Metastatic Bladder Squamous Cell Carcinoma, Metastatic Kidney Medullary Carcinoma, Metastatic Malignant Genitourinary System Neoplasm, Metastatic Penile Carcinoma, Metastatic Sarcomatoid Renal Cell Carcinoma, Stage IV Bladder Cancer AJCC v8, Stage IV Penile Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Stage IVB Prostate Cancer AJCC v8, Bladder Clear Cell Adenocarcinoma, Bladder Neuroendocrine Carcinoma, Collecting Duct Carcinoma, Metastatic Urethral Carcinoma, Stage IV Urethral Cancer AJCC v8, Urethral Clear Cell Adenocarcinoma, Bladder Small Cell Neuroendocrine Carcinoma, Metastatic Bladder Small Cell Neuroendocrine Carcinoma, Metastatic Prostate Small Cell Neuroendocrine Carcinoma, Invasive Bladder Giant Cell Urothelial Carcinoma, Invasive Bladder Lymphoepithelioma-Like Carcinoma, Invasive Bladder Nested Urothelial Carcinoma, Invasive Bladder Plasmacytoid Urothelial Carcinoma, Invasive Bladder Sarcomatoid Urothelial Carcinoma, Invasive Bladder Urothelial Carcinoma, Metastatic Bladder Clear Cell (Glycogen-Rich) Urothelial Carcinoma, Metastatic Bladder Lipid-Rich Urothelial Carcinoma, Metastatic Bladder Micropapillary Urothelial Carcinoma, Metastatic Bladder Plasmacytoid Urothelial Carcinoma, Metastatic Bladder Sarcomatoid Urothelial Carcinoma, Urachal Adenocarcinoma, Malignant Testicular Leydig Cell Tumor, Malignant Testicular Sertoli Cell Tumor, Metastatic Bladder Giant Cell Urothelial Carcinoma, Metastatic Chromophobe Renal Cell Carcinoma, Metastatic Papillary Renal Cell Carcinoma
UT Southwestern
(CLONEVO): Cell cycLe inhbitiON to Target the EVolution of UrOthelial Cancer (CLONEVO)
Single-arm, open-label window-of-opportunity trial of neoadjuvant Abemaciclib in 20 patients, with tumor tissue obtained as standard of care at tumor resection (pre-Abemaciclib) and cystectomy (post-Abemaciclib)
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
42296
All
18 Years and over
Early Phase 1
NCT03837821
STU-2022-1068
Inclusion Criteria
• Age ≥ 18 years old at time of informed consent
• Histologically confirmed MIBC (T2-T4) pure or mixed histology urothelial carcinoma [urothelial carcinoma should be the dominant (>50%) histology].
• Refusing cisplatin-based chemotherapy or ineligible for cisplatin-based chemotherapy due to at least one of the following:
• Creatinine clearance < 60 mL/min (by Cockcroft-Gault calculation and/or measured creatinine clearance)
• Hearing loss ≥ grade 2 by CTCAE criteria and/or;
• Neuropathy ≥ grade 2 by CTCAE criteria and/or
• Heart failure NYHA ≥ III
• Medically fit for TURBT and radical cystectomy
• Adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1.5 K/mm3
• White blood cell count (WBC) > 3.0 K/mm3
• Platelets ≥ 100 K/mm3
• Hemoglobin ≥ 9 g/dL
• Serum total bilirubin ≤ 1.5 x ULN (Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted)
• ALT and AST ≤ 3.0 x ULN
• Ability to swallow oral medications
• Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization Exclusion Criteria
• Patients with locally advanced unresectable or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within from the date of signed consent, 28 days prior to study enrollment. Low volume (<1.5 cm) suspicious lymph node metastases in the pelvis are allowed if they are in the LN dissection template field. The required radiographic imaging includes:
• Abdomen/pelvis - CT/MRI
• Chest - chest x-ray or CT scan
• Bone scan or FDG-PET/CT in the presence of bone pain or unexplained elevated alkaline phosphatase
• Patients with another active second malignancy other than non-melanoma skin cancers and localized prostate cancer. Patients that have completed all necessary therapy and are considered to be <30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment.
• Patients who have received anti-cancer therapy including chemotherapy, radiotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks or 5 half-lives, whichever is longer, prior to starting study drug. Patients who received chemotherapy must have recovered to CTCAE Grade ≤1 from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Cycle 1 Day 1. Patients currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor not to be scientifically or medically compatible with this study are also excluded.
• Patients who have serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• Patients who have had major surgery within 14 days prior to Cycle 1 Day 1.
• Have an active bacterial infection (especially if requiring IV antibiotics), systemic fungal and/or known viral infection (for example, human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies).
• Subjects who received a strong CYP3A inhibitor within 7 days prior to the first dose of study drug, or patients who require continuous treatment with a strong CYP3A inhibitor
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Pregnant or breast-feeding women
• Women who do not agree to use a medically approved contraceptive method during the treatment period and for 3 weeks following the last dose of Abemaciclib
• Men who do not agree to use a reliable method of birth control and to not donate sperm during the study and for at least 3 months following the last dose of Abemaciclib
• Subjects unwilling or unable to comply with the protocol
• Age ≥ 18 years old at time of informed consent
• Histologically confirmed MIBC (T2-T4) pure or mixed histology urothelial carcinoma [urothelial carcinoma should be the dominant (>50%) histology].
• Refusing cisplatin-based chemotherapy or ineligible for cisplatin-based chemotherapy due to at least one of the following:
• Creatinine clearance < 60 mL/min (by Cockcroft-Gault calculation and/or measured creatinine clearance)
• Hearing loss ≥ grade 2 by CTCAE criteria and/or;
• Neuropathy ≥ grade 2 by CTCAE criteria and/or
• Heart failure NYHA ≥ III
• Medically fit for TURBT and radical cystectomy
• Adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥ 1.5 K/mm3
• White blood cell count (WBC) > 3.0 K/mm3
• Platelets ≥ 100 K/mm3
• Hemoglobin ≥ 9 g/dL
• Serum total bilirubin ≤ 1.5 x ULN (Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted)
• ALT and AST ≤ 3.0 x ULN
• Ability to swallow oral medications
• Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization Exclusion Criteria
• Patients with locally advanced unresectable or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within from the date of signed consent, 28 days prior to study enrollment. Low volume (<1.5 cm) suspicious lymph node metastases in the pelvis are allowed if they are in the LN dissection template field. The required radiographic imaging includes:
• Abdomen/pelvis - CT/MRI
• Chest - chest x-ray or CT scan
• Bone scan or FDG-PET/CT in the presence of bone pain or unexplained elevated alkaline phosphatase
• Patients with another active second malignancy other than non-melanoma skin cancers and localized prostate cancer. Patients that have completed all necessary therapy and are considered to be <30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment.
• Patients who have received anti-cancer therapy including chemotherapy, radiotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks or 5 half-lives, whichever is longer, prior to starting study drug. Patients who received chemotherapy must have recovered to CTCAE Grade ≤1 from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Cycle 1 Day 1. Patients currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor not to be scientifically or medically compatible with this study are also excluded.
• Patients who have serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• Patients who have had major surgery within 14 days prior to Cycle 1 Day 1.
• Have an active bacterial infection (especially if requiring IV antibiotics), systemic fungal and/or known viral infection (for example, human immunodeficiency virus antibodies, hepatitis B surface antigen, or hepatitis C antibodies).
• Subjects who received a strong CYP3A inhibitor within 7 days prior to the first dose of study drug, or patients who require continuous treatment with a strong CYP3A inhibitor
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Pregnant or breast-feeding women
• Women who do not agree to use a medically approved contraceptive method during the treatment period and for 3 weeks following the last dose of Abemaciclib
• Men who do not agree to use a reliable method of birth control and to not donate sperm during the study and for at least 3 months following the last dose of Abemaciclib
• Subjects unwilling or unable to comply with the protocol
Drug: Abemaciclib
Bladder Cancer, Urinary Bladder
UT Southwestern
Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Bacillus Calmette-Guerin (BCG) in High-Risk Non-Muscle Invasive Bladder Cancer (HR NMIBC) (MK-3475-676/KEYNOTE-676)
This study is designed to assess the antitumor efficacy and safety of pembrolizumab in combination with BCG, compared to BCG monotherapy, in participants with HR NMIBC that is either persistent or recurrent following adequate BCG induction (Cohort A), or that is naïve to BCG treatment (Cohort B). The primary hypothesis for Cohort A is that the combination of pembrolizumab plus BCG has a superior complete response rate (CRR) as assessed by central pathology review compared to BCG in participants with carcinoma in situ (CIS). The primary hypothesis for Cohort B is that the combination of pembrolizumab plus BCG (either reduced maintenance or full maintenance) has a superior Event Free Survival (EFS) compared to BCG.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Solomon Woldu
154531
All
18 Years and over
Phase 3
NCT03711032
STU-2020-0225
Inclusion Criteria:
• Have locally and blinded independent central review (BICR)-confirmed histological diagnosis of high-risk non-muscle invasive (T1, high grade Ta and/or CIS) UC of the bladder
• Has undergone cystoscopy/ transurethral resection of bladder tumor (TURBT) to remove all resectable disease
• Has provided tissue for biomarker analysis
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Has adequate organ function
• During the treatment period and for ≥7 days after the last dose of BCG, male participants are EITHER abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR, must agree to use contraception unless confirmed to be azoospermic
• Female participants who are not pregnant, not breastfeeding, and either not a woman of child bearing potential (WOCBP); or are a WOCBP who agrees to use a contraception method that is highly effective or remains abstinent from heterosexual intercourse during the treatment period and for ≥7 days after the last dose of BCG or 120 days after the last dose of pembrolizumab, whichever comes last BCG Post-induction Cohort (Cohort A) Only
• Has been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC
• Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC
Exclusion Criteria:
• Has a history of or concurrent locally advanced (i.e., T2, T3, T4) or metastatic UC
• Has concurrent extra-vesical (i.e, urethra, ureter, renal pelvis) non-muscle invasive urothelial carcinoma or a history of extra-vesical non-muscle invasive UC
• Has received prior therapy with 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
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks of start of study treatment
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of start of study treatment
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of start of study treatment
• Has a known additional malignancy that is progressing or requires active treatment within the past 3 years
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has one or more of the following contraindications to BCG: prior BCG sepsis or systemic infection, total bladder incontinence, or an adverse experience to a previous BCG instillation that resulted in treatment discontinuation and precludes retreating with BCG
• Has an active infection or diagnosis requiring systemic antimicrobial therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of Hepatitis B or known active Hepatitis C virus infection
• Has current active tuberculosis
• Has had an allogenic-tissue/solid organ transplant
• Has any contraindication(s) to IV contrast or is otherwise unable to have screening imaging with IV contrast performed BCG Post-induction Cohort (Cohort A) Only - Has persistent T1 disease following an induction course of BCG BCG Naïve Cohort (Cohort B) Only
• Has received any prior treatment with BCG for their NMIBC within the past 2 years prior to study entry
Biological: Pembrolizumab, Biological: BCG
High-risk Non-muscle Invasive Bladder Cancer
programmed cell death receptor 1 (PD-1), programmed cell death ligand 1 (PD-L1), anti-PD-1, anti-PD-L1, BCG, HR NMIBC, Patient Reported Outcome (PRO)
UT Southwestern
Gemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations
This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, 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.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
42296
All
18 Years and over
Phase 2
NCT03609216
STU-2020-0422
Inclusion Criteria:
• Step 1 Patient Registration Eligibility Criteria
• Histologically confirmed muscle-invasive urothelial carcinoma of the bladder. 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 examination under anesthesia (EUA). The diagnostic TURBT sample must have been obtained within 60 days prior to registration
• 20 unstained slides (10 micron thickness) of formalin-fixed paraffin-embedded (FFPE) pre-treatment diagnostic transurethral resection (TUR) specimen available (for sequencing), with 2 (5 micron) slides at the start and end of the 20 slides, for a total of 22 unstained slides. An FFPE block is also acceptable
• Clinical stage T2-T4aN0/xM0 disease
• Medically appropriate candidate for radical cystectomy as assessed by surgeon
• No concomitant multifocal carcinoma in situ; a single focus is allowed
• A single muscle-invasive bladder tumor measuring ≤5 cm in size as defined by the surgeons at cystoscopic evaluation. When documented, pathologic size at cystoscopy and TURBT will take precedence over radiographic measurements of tumor size.
• No clinical or radiographic evidence for locally advanced or metastatic disease
• No prior anti-PD-1 or anti PD-L1 therapies, or systemic chemotherapy within the past 5 years (prior intravesical induction immunotherapy for non-muscle invasive disease is allowed, defined as BCG x6 doses and maintenance therapy); BCG refractory disease, defined as disease recurrence within 3 months of BCG therapy, is not allowed. Intravesical chemotherapy is allowed.
• No prior radiation therapy to the bladder or prostate
• No major surgery or radiation therapy =< 4 weeks of registration (TURBT is allowed).
• Not pregnant and not nursing. This study involves an agent that has known genotoxic, mutagenic and teratogenic effects. For women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Platelet count >= 100,000/mm^3
• Calculated creatinine clearance ≥ 55 mL/min using formula per institutional standard or investigator's discretion. The same formula should be used to calculate all subsequent creatinine clearances.
• Total bilirubin =< 1.5 x upper limit of normal (ULN) * (For patients with documented Gilbert's syndrome Total Bilirubin =< 3 x ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
• Alkaline phosphatase =< 2.5 x ULN
• No evidence of New York Heart Association (NYHA) functional class III or IV heart disease
• No ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade >= 2
• No pre-existing sensory grade >= 2 neuropathy
• No pre-existing grade >= 2 hearing loss
• No serious intercurrent medical or psychiatric illness, including serious active infection
• None of the following within the 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
• No known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the drugs used in this trial. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy, when indicated
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to the agents used in this study
• No concurrent treatment on another clinical trial; supportive care trials or non-therapeutic trials (e.g., quality of life) are allowed
• No prior malignancy except for: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years. Patients with localized prostate cancer who are being followed by an active surveillance program are also eligible
• Step 2 Patient Registration Eligibility Criteria
• Patients must have completed 4 or more cycles of protocol-directed chemotherapy and DDR gene results must be available
• Step 3 Patient Registration Eligibility Criteria (only patients with a DDR gene alteration)
• Deleterious alteration within 1 or more of 9 pre-defined DDR genes within the pre-treatment TURBT deoxyribonucleic acid (DNA)
• Cystoscopy and imaging performed to determine stage/treatment assignment
Drug: Gemcitabine Hydrochloride, Drug: Cisplatin, Biological: Pegfilgrastim, Procedure: Conventional Surgery, Procedure: Radical Cystectomy, Other: Chemoradiotherapy
Infiltrating Bladder Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma, Stage III Bladder Urothelial Carcinoma, Urinary Bladder
UT Southwestern
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) (LIBRETTO-001)
This is an open-label, first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of selpercatinib (also known as LOXO-292) administered orally to participants with advanced solid tumors, including rearranged during transfection (RET)-fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
206021
All
12 Years and over
Phase 1/Phase 2
NCT03157128
STU 082018-008
Key
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer therapy is permitted Note: Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Participants are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds (msec)
• Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes.
• Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.
Inclusion Criteria:
For Phase 1:
• Participants with a locally advanced or metastatic solid tumor that:
• Has progressed on or is intolerant to standard therapy, or
• For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
• Decline standard therapy
• Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
• A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
• Measurable or non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type
• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than [<] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
• Adequate hematologic, hepatic and renal function
• Life expectancy of at least 3 months For Phase 2: As for phase 1 with the following modifications:
• For Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
• Cohorts 1 and 2:
• Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
• At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
• Cohorts 3 and 4: Enrollment closed
• Cohort 5:
• Cohorts 1-4 without measurable disease
• MCT not meeting the requirements for Cohorts 3 or 4
• MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval
• cfDNA positive for a RET gene alteration not known to be present in a tumor sample
• Cohort 6: Participants who otherwise are eligible for Cohorts 1, 2 or 5 who discontinued another RET inhibitor may be eligible with prior Sponsor approval
• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC Key Exclusion Criteria (Phase 1 and Phase 2):
• Phase 2 Cohorts 1 and 2: an additional known oncogenic driver
• Cohorts 3 and 4: Enrollment closed
• Cohorts 1, 2 and 5: prior treatment with a selective RET inhibitor Notes: Participants otherwise eligible for Cohorts 1, 2, and 5 who discontinued another selective RET inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval
• Investigational agent or anticancer therapy (including chemotherapy, biologic therapy, immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 (selpercatinib). In addition, no concurrent investigational anti-cancer therapy is permitted Note: Potential exception for this exclusion criterion will require a valid scientific justification and approval from the Sponsor
• Major surgery (excluding placement of vascular access) within 2 weeks prior to planned start of LOXO-292 (selpercatinib)
• Radiotherapy with a limited field of radiation for palliation within 1 week of planned start of LOXO-292 (selpercatinib), with the exception of participants receiving radiation to more than 30% of the bone marrow or with a wide field of radiation, which must be completed at least 4 weeks prior to the first dose of study treatment
• Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy
• Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression. Participants are eligible if neurological symptoms and CNS imaging are stable and steroid dose is stable for 14 days prior to the first dose of LOXO-292 (selpercatinib) and no CNS surgery or radiation has been performed for 28 days, 14 days if stereotactic radiosurgery (SRS)
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of LOXO-292 (selpercatinib) or prolongation of the QT interval corrected (QTcF) greater than (>) 470 milliseconds (msec)
• Participants with implanted pacemakers may enter the study without meeting QTc criteria due to nonevaluable measurement if it is possible to monitor for QT changes.
• Participants with bundle branch block may be considered for study entry if QTc is appropriate by a formula other than Fridericia's and if it is possible to monitor for QT changes.
• Required treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and certain prohibited concomitant medications
• Phase 2 Cohort 7 (neoadjuvant treatment): Participant must not have received prior systemic therapy for NSCLC.
Drug: LOXO-292
Lymphoma, Non-Small Cell Lung Cancer, Colon Cancer, Medullary Thyroid Cancer, Any Solid Tumor, Brain and Nervous System, Eye and Orbit, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, 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, Stomach, Thyroid, Urinary Bladder, Hodgkins Lymphoma, Small Intestine, Soft Tissue
LOXO-292, KIF5B-RET, M918T, CCDC6-RET, RET-PTC1, NCOA4-RET, RET-PTC, RET-PTC3, RET-PTC4, PRKAR1A-RET, RET-PTC2, GOLGA5-RET, RET-PTC5, ERC1-RET, KTN1-RET, RET-PTC8, HOOK3-RET, PCM1-RET, TRIM24-RET, RET-PTC6, TRIM27-RET, TRIM33-RET, RET-PTC7, AKAP13-RET, FKBP15-RET, SPECC1L-RET, TBL1XR1-RET, BCR-RET, FGRF1OP-RET, RFG8-RET, RET-PTC9, ACBD5-RET, MYH13-RET, CUX1-RET, KIAA1468-RET, FRMD4A-RET, SQSTM1-RET, AFAP1L2-RET, PPFIBP2-RET, EML4-RET, PARD3-RET, G533C, C609F, C609G, C609R, C609S, C609Y, C611F, C611G, C611S, C611Y, C611W, C618F, C618R, C618S, C620F, C620R, C620S, C630R, C630Y, D631Y, C634F, C634G, C634R, C634S, C634W, C634Y, K666E, E768D, L790F, V804L, V804M, A883F, S891A, R912P, CLIP1-RET, Y806C, RET fusion, RET alteration, RET mutation, RET rearrangement, RET translocation, Neoplasms by Site, Neoplasms, Non-Small Cell Lung Cancer, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Cancer of Lung, Cancer of the Lung, Lung Cancer, Neoplasms, Lung, Neoplasms, Pulmonary, Pulmonary Cancer, Pulmonary Neoplasms, Respiratory Tract Neoplasms, Lung Diseases, Respiratory Tract Diseases, Carcinoma, Bronchogenic, Bronchial Neoplasms, Medullary Thyroid Cancer, Papillary Thyroid Cancer, Thyroid Diseases, Thyroid Neoplasms, Cancer of the Thyroid, Cancer of Thyroid, Neoplasms, Thyroid, Thyroid Ademona, Thyroid Cancer, Thyroid Carcinoma, Endocrine System Diseases, Endocrine Gland Neoplasms, Head and Neck Neoplasms, Thoracic Neoplasms, CNS tumor, Primary CNS tumor, Cancer of Colon, Cancer of the Colon, Colon Cancer, Colon Neoplasms, Colonic Cancer, Neoplasms, Colonic, Malignant tumor of Breast, Mammary Cancer, Mammary Carcinoma, Human, Mammary Neoplasm, Human, Neoplasms, Breast, Tumors, Breast, Human Mammary Carcinoma, Malignant Neoplasm of Breast, Breast Carcinoma, Breast Tumors, Cancer of the Breast, Breast Neoplasms, Breast Cancer, RET Inhibitor, MTC, NSCLC, selpercatinib, neo-adjuvant treatment in early stage NSCLC
UT Southwestern
Stereotactic Radiosurgery (SRS) Dose-Escalation Study for Brain Metastasis (SRS)
SRS dose escalation for brain metastases in radiation-naïve patients will establish true tolerable doses, which may exceed the current standard doses. This may lead to an improvement in local control, patient survival, and/or quality-of life.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Robert Timmerman
69821
All
18 Years and over
N/A
NCT02645487
STU 022015-106
Inclusion Criteria
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, 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).
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy < 3 months.
• 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 must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Biopsy-proven non-hematopoietic malignancy, except for small cell lung cancer, germ cell cancer, or unknown primary tumor.
• Radiographic evidence by MRI (or by CT scan with CT contrast if ineligible or intolerant of MRI) of brain metastasis. (If patient is unable to tolerate MRI contrast, an MRI without contrast is acceptable if lesions are visible)
• All brain metastases must be outside the brain stem (midbrain, pons and medulla).
• Patient must have 10 or less brain metastases.
• The maximum diameter of any lesion must be less than or equal to 3.0 cm.
• Previous treatment with surgery, radiation, chemotherapy, immunotherapy or any targeted agents are allowed provided that:
• Radiation was not to the brain.
• Surgery to the brain was > 7 days prior to SRS and there remains at least one additional brain metastasis that can be targeted with SRS
• Age ≥ 18 years.
• ECOG Performance Score of 2 or better/Karnofsky Performance Status score of 50-60 or better.
• All men, as well as women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, 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).
• Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria
• Patients had craniotomy and surgery to the brain within 7 days from the date of SRS.
• Patients with leptomeningeal metastasis. NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
• Patients with a contraindication to both MRI (with or without contrast) and CT scan (with contrast)
• Patients with life expectancy < 3 months.
• 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 must not be pregnant or nursing at the time of SRS treatment due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
Radiation: Stereotactic Radiosurgery
Brain Neoplasms, Adult, Malignant, Lymphoma, Sarcoma, Multiple Myeloma, Brain and Nervous System, Other, Eye and Orbit, Anklylosing Spondylitis, Anus, Bones and Joints, Breast - Female, Breast - Male, 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, Hodgkins Lymphoma, Lymphoid Leukemia, Small Intestine, Soft Tissue
UT Southwestern; Parkland Health & Hospital System