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55 Study Matches
A Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors
The main purpose of the study is to assess whether the study drug, LY4066434, is safe and tolerable when administered to participants with locally advanced or metastatic solid tumors with certain KRAS mutations. LY4066434 will be given alone or in combination with other treatments. The study will have 2 parts: monotherapy dose escalation and dose optimization. The study is expected to last up to approximately 5 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Syed Kazmi
ALL
18 Years to old
PHASE1
NCT06607185
STU-2024-1087
Inclusion Criteria:
* Have evidence of KRAS G12C, G12D, G12V, G12A, G12S, or G13D mutation in tumor tissue or circulating tumor DNA
* Histological or cytologically proven diagnosis of a locally advanced, unresectable, and/or metastatic solid tumor cancer
* Have measurable disease per RECIST 1.1
* Have an ECOG performance status of ≤1
* Must not be pregnant and/or planning to breastfeed during the trial or within 180 days of the last dose of trial intervention
* Must be able to swallow tablets
* Participants with asymptomatic or treated CNS disease may be eligible
Exclusion Criteria:
* Have known active CNS metastases and/or carcinomatous meningitis
* Have any unresolved toxicities from prior therapy greater than NCI CTCAE Version 5.0 Grade 1 at the time of starting trial treatment, except for alopecia, peripheral neuropathy and ongoing endocrinopathies controlled on appropriate replacement therapy
* Have significant cardiovascular disease defined as unstable angina or acute coronary syndrome, history of myocardial infarction, known left ventricular ejection fraction or heart failure, uncontrolled or symptomatic arrhythmias.
* Have known active hepatitis B virus (HBV), hepatitis C virus (HCV) and untreated HIV infection
* Have other active malignancy unless in remission with life expectancy greater than 2 years.
* Have active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
* Have history of non-infectious pneumonitis/interstitial lung disease that received steroids or has current clinically significant pneumonitis/interstitial lung disease DRUG: LY4066434., DRUG: Cetuximab, DRUG: Nab paclitaxel, DRUG: Gemcitabine, DRUG: Oxaliplatin, DRUG: Leucovorin, DRUG: Irinotecan, DRUG: 5Fluorouracil, DRUG: Carboplatin, DRUG: Cisplatin, DRUG: Pemetrexed, DRUG: Pembrolizumab
Pancreatic Ductal Adenocarcinoma, Non-Small Cell Lung Cancer, Colorectal Cancer, Advanced Solid Tumor, Metastatic Solid Tumor, Anus, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Gall Bladder, 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, Small Intestine, Soft Tissue, Stomach, Thyroid, Urinary Bladder
KRAS, KRAS mutation, KRASG12C, KRASG12D, KRASG12V, KRASG12S, KRASG12A, KRASG13D, LY4066434, Targeted therapy, Lung cancer, Pancreas cancer, Colon cancer, Rectal cancer, Colorectal cancer, Ovarian cancer, Endometrial cancer, Cholangiocarcinoma, Esophageal cancer, KRAS-mutant tumor
UT Southwestern
Radiotherapy in Combination With Checkpoint Inhibition for Patients With Metastatic Kidney Cancer (SPARK)
To evaluate progression of metastatic renal cell carcinoma from the initiation of PULSAR radiotherapy in combination with IMSA101 injectable onward.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Raquibul Hannan
ALL
18 Years to old
PHASE2
NCT06601296
STU-2024-0919
Inclusion Criteria:
* Patients must have metastatic ccRCC.
* Patients must have oligoprogression defined as progression in ≤3 lesions.
* All oligoprogression lesions must be suitable for radiation.
* Patients must have at least one site of disease that can be safely injected with IMSA101. Lung metastases are excluded.
* ECOG performance status 0-2.
* Age ≥ 18 years.
* Patients must have adequate organ and marrow function within 14 days prior to study entry.
* All IMDC risk categories are allowed.
Exclusion Criteria:
* Patients with progressive ultracentral/central chest lesions will be excluded DRUG: IMSA101
Metastatic Renal Cell Carcinoma ( mRCC), OligoProgressive Metastatic Disease, Kidney
renal, kidney, mrcc, metastatic, cancer, STING, PULSAR, SABr, SPARK, nivolumab, IMSA 101
UT Southwestern
A Novel Approach for Reducing Hyperoxaluria and Kidney Stone Risk.
This pilot study is proposing a novel approach to directly target intestinal oxalate absorption with the drug Tenapanor, which was recently FDA-approved for treating hyperphosphatemia in patients with chronic kidney disease. Tenapanor works by blocking paracellular phosphate absorption by the intestine, but the underlying mechanisms have not been clearly defined. Since phosphate and oxalate ions are absorbed through the same paracellular pathway, and are of similar size and charge, Tenapanor is hypothesized to also reduce dietary oxalate absorption and consequently lower urinary oxalate excretion.
Call 214-648-5005
studyfinder@utsouthwestern.edu, vidiya.srikakulapu@UTSouthwestern.edu
Jonathan Whittamore
ALL
18 Years to 99 Years old
PHASE4
NCT06481150
STU-2023-1257
Inclusion Criteria:
* Normal, healthy adult volunteers
Exclusion Criteria:
* Personal history of kidney stones
* Pregnant or nursing
* Recurrent urinary tract infections
* Lithogenic urine chemistry at baseline (oxalate \> 45 mg/24 h, urine calcium \> 300 mg/24 h)
* Chronic kidney disease (eGFR \< 90 mL/min/1.73m2)
* Personal history of GI disease, GI obstruction, or GI surgery
* Chronic diarrhea
* Intestinal inflammation (Fecal calprotectin \> 120 mcg/g)
* Drugs which are substrates of OATP2B1 (e.g. enalapril)
* Chronic use of sodium polystyrene sulfonate, angiotensin-converting enzyme inhibitors, diuretics, antacids, alkali treatment, or carbonic anhydrase inhibitors. DRUG: Tenapanor, OTHER: Placebo
Hyperoxaluria
UT Southwestern
The ROle of Compression StocKings in Heart Failure Patients (ROCK-HF)
Congestive heart failure (CHF) occurs when the heart is weak and not able to effectively pump blood to the body. One of the common manifestations of CHF is fluid overload and swelling of the legs. Diuretics or "water pills" are usually the treatment for fluid overload and leg swelling; however, in some patients' diuretics are no longer effective or the effectiveness is limited due to poor kidney function. The presence of chronic swelling of the legs could potentially damage the veins; additionally, it could lead to chronic skin changes in the legs and in the worst cases to a leg ulcer. Compression stockings are used in patients with venous diseases to reduce the swelling of the legs and improve mobility and quality of life. Although, there is a theoretical risk that compression stockings might push the fluid of the legs back to the heart and lungs worsening the CHF. The purpose of this study is to determine whether the use of knee-high tight socks (tight stockings with strong compression) vs. knee-high soft socks (soft stockings with minimum compression) are effective in preventing swelling and skin changes and safe in patients with CHF. During the first visit (in-person) a routine medical test will be performed including blood tests, review of the medication doses, current weight, an ultrasound images of the veins, (venous reflux ultrasound), questions about health status and a brief physical exam. The participants will be randomly assigned to receive tight compression vs. soft compression socks. Participants will be asked to wear the socks at least 8 hours a day for 5 days a week. There will be a total of 3 virtual visit (by video or telephone); the first one after one week, then after one month and two months. During the virtual visit participants will be asked about symptoms, current medications and doses, and current weight. The participants are expected to return to the clinic after 3 months for a second in-person visit. During this visit the investigators will ask questions about participant's health, they will perform a brief physical exam of their legs, and check participants weight and medicines; also, a venous ultrasound of the legs, questions about health status will be performed. The duration of the study is 3 months.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Rafael.Cires-Drouet@UTSouthwestern.edu
Rafael Cires-Drouet
ALL
18 Years to old
NA
NCT06350695
STU-2024-0855
Inclusion Criteria:
* Age 18 years and older
* Diagnosis of Heart failure NYHA II-III Class A, B, or C.
* Pitting edema of the lower extremities
Exclusion Criteria:
* Peripheral arterial disease with ABI of 0.5 or less
* Severe decompensated heart failure NYHA IV
* Unstable acute coronary syndrome
* Severe valvular stenosis or regurgitation
* Hypertrophic obstructive cardiomyopathy
* Unstable arrhythmia without a defibrillator
* On renal replacement therapy, hemodialysis of peritoneal dialysis
* Morbid obesity with a BMI \> 40
* Pregnancy
* Lymphedema or Lipoedema
* Unable to put the compression stockings on by him/ herself or a person to do it for the patient
* Septic phlebitis, acute bacterial, viral or allergic inflammation of the legs
* Expectancy of life less than 6 months
* Unable to read or understand English language DEVICE: low grade compression stockings (10-15 mmHg), DEVICE: high grade compression stockings (20-30 mmHg)
Heart Failure，Congestive, Leg Edema, Venous Insufficiency, Venous Ulcers
compression stockings, congestive heart failure, venous insufficiency, edema of the legs, venous ulcers
A Clinical Study of Intismeran Autogene (V940) Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005)
Researchers are looking for new ways to treat people with high-risk muscle-invasive urothelial carcinoma (MIUC). Urothelial carcinoma is a type of bladder cancer that begins in cells that line the inside of the bladder and other parts of the urinary tract, such as part of the kidneys, ureters, and urethra. People with MIUC usually have chemotherapy before surgery, then surgery to remove the cancer. Chemotherapy is a type of medicine to destroy cancer cells or stop them from growing. After surgery, some people receive more treatment to prevent cancer from returning. Pembrolizumab is an immunotherapy, which is a treatment that helps the immune system fight cancer. Enfortumab vedotin (EV) is an antibody drug conjugate (ADC). An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. Researchers want to learn if giving intismeran autogene (the study treatment) with pembrolizumab can prevent MIUC from returning after surgery. Intismeran autogene (also called mRNA-4157) is designed to treat each person's cancer by helping the person's immune system identify and kill cancer cells based on certain proteins found on those cancer cells. The goals of this study are to learn if people who receive intismeran autogene and pembrolizumab are alive and cancer free longer than those who receive placebo and pembrolizumab, and to learn about the safety of intismeran autogene, pembrolizumab, and EV, and if people tolerate them.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Waddah Arafat
ALL
18 Years to old
PHASE1
NCT06305767
STU-2024-0447
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Has a histological diagnosis of urothelial carcinoma (UC)
* Must provide blood samples per protocol, to enable intismeran autogene production, and circulating tumor deoxyribonucleic acid testing
* Has an Eastern Cooperative Oncology Group performance status of 0 to 2 assessed within 7 days before randomization
* Must provide a formalin-fixed paraffin-embedded tumor tissue sample for next generation sequencing
Adjuvant Cohort:
* Has MIUC
* Has high-risk pathologic disease after radical resection
* For participants who have not received cisplatin-based neoadjuvant chemotherapy, are ineligible to receive cisplatin according to protocol pre-defined criteria
Perioperative Cohort:
* Has MIBC
* Is deemed eligible for RC and PLND and agrees to undergo curative intent standard RC and PLND and neoadjuvant and adjuvant treatment per protocol
* Is ineligible to receive cisplatin according to protocol pre-defined criteria
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has known additional malignancy that is progressing or has required active treatment ≤3 years prior to study randomization
* Has current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy
* Has active hepatitis B and hepatitis C virus infection
Adjuvant Cohort:
* Has received prior systemic anticancer therapy
* Has received prior neoadjuvant therapy, with the exception of neoadjuvant cisplatin-based chemotherapy for MIUC
* Has severe hypersensitivity to either intismeran autogene or pembrolizumab (MK-3475) and/or any of their excipients
Perioperative Cohort:
* Has received any prior systemic treatment, cancer vaccine treatment, chemoradiation, and/or radiation therapy treatment for MIBC
* Has severe hypersensitivity to either intismeran autogene, pembrolizumab, or EV and/or any of their excipients
* Has ongoing sensory or motor neuropathy
* Has active keratitis or corneal ulcerations BIOLOGICAL: Pembrolizumab, BIOLOGICAL: Intismeran autogene, OTHER: Placebo, BIOLOGICAL: Enfortumab Vedotin, PROCEDURE: Surgery (RC plus PLND)
Bladder Cancer, Urinary Bladder
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
UT Southwestern
A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors (EXCEED)
The purpose of this study is to find out whether the study drug, LY4101174, is safe, tolerable and effective in participants with select advanced or metastatic solid tumors. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE1
NCT06238479
STU-2024-0162
Inclusion Criteria:
* Have one of the following solid tumor cancers:
* Cohort A1: urothelial carcinoma, triple negative breast cancer, non-small cell lung cancer, esophageal cancer, pancreatic cancer, ovarian cancer, cervical cancer (squamous cell carcinoma), head and neck squamous cell carcinoma or prostate cancer
* Cohort A2/B1/B2: urothelial carcinoma
* Cohort C1: triple negative breast cancer
* Cohort C2: non-small cell lung cancer
* Cohort C3: ovarian or fallopian tube cancer
* Cohort C4: cervical cancer
* Cohort C5: head and neck squamous cell carcinoma
* Prior Systemic Therapy Criteria:
* Cohort A1/C1-5: Individual has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating investigator; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies
* Cohort A2/B1/B2: Individual must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
* Prior enfortumab vedotin specific requirements:
* Cohorts A1/A2/C1-5: prior treatment with enfortumab vedotin is allowed, but not required
* Cohort B1: individual must be enfortumab vedotin naive in the advanced/metastatic setting
* Cohort B2: individual must have received enfortumab vedotin in the metastatic/advanced setting.
* Measurability of disease
* Cohort A1: measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1)
* Cohorts A2, B1, B2, C1-5: measurable disease required as defined by RECIST v1.1
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country specific regulations
Exclusion Criteria:
* Individual with known or suspected uncontrolled CNS metastases
* Individual with uncontrolled hypercalcemia
* Individual with uncontrolled diabetes
* Individual with evidence of corneal keratopathy or history of corneal transplant
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Current of history of intestinal obstruction in the previous 3 months
* Recent thromboembolic event and/or clinically significant bleeding
* Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
* History of pneumonitis/interstitial lung disease
* History of Grade ≥3 skin toxicity when receiving enfortumab vedotin
* Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention
* Individual with active uncontrolled infection DRUG: LY4101174
Metastatic Solid Tumor, Recurrent Solid Tumor, Advanced Solid Tumor, Urinary Bladder Neoplasm, Triple Negative Breast Cancer, Non-Small Cell Lung Cancer, Esophageal Cancer, Pancreatic Cancer, Ovarian Cancer, Cervical Cancer, Head and Neck Squamous Cell Carcinoma, Prostate Cancer, Renal Pelvis Cancer, Bladder Cancer, Breast - Female, Breast - Male, Cervix, Esophagus, Larynx, Lip, Oral Cavity and Pharynx, Lung/Thoracic, Ovary, Pancreas, Prostate, Urinary Bladder
Bladder Cancer, Bladder Neoplasm, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Urothelial Neoplasms, Renal Pelvis Cancer, Ureter Cancer, Nectin-4, Antibody Drug Conjugate (ADC)
UT Southwestern
Intra-nasal Ketorolac for Acute Ureteral Stent-associated Pain Following Ureteroscopy for Stone Disease
Objective: To improve quality-of-life and health care delivery to patients receiving ureteral stents. Specific Aims: Evaluate the feasibility, practicality, and qualitative outcomes of utilizing intra-nasal ketorolac in patients with indwelling ureteral stents (Phase I), followed by a randomized trial comparing two non-steroidal anti-inflammatory drugs, intra-nasal Ketorolac versus oral Diclofenac. Hypotheses: Due to its favorable pharmacokinetics in relieving acute pain, investigators expect improved pain scores and a lower rate of unplanned clinical encounters in patients receiving intra-nasal ketorolac compared to those taking oral diclofenac following ureteroscopic surgery for urolithiasis. Study Rationale: Following ureteroscopic management of urolithiasis, patient with indwelling ureter stents have higher levels of discomfort compared to those without a ureter stent. Prior studies showed that intramuscular Ketorolac at time of ureter stent removal decreased the incidence of unplanned clinical encounters. Furthermore, onset of analgesic effect by intra-nasal ketorolac is faster than its oral form, and similar its intramuscular and intravenous counterparts.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Isaac.Palma-Zamora@UTSouthwestern.edu
Brett Johnson
ALL
18 Years and over
PHASE1
NCT06158620
STU-2023-0775
Inclusion Criteria:
* ≥18 years old
* English-speaking
* Candidate for unilateral ureteroscopy for treatment of urolithiasis
* Surgical plan includes placement of a ureteral stent
Exclusion Criteria:
* Pregnant/nursing, prisoners, cognitively impaired
* Solitary kidney
* Stone in transplant kidney
* Anatomic abnormalities (i.e., ureteral stricture, infundibular stenosis, uretero-pelvic junction obstruction, horseshoe kidney, duplicated system)
* History of ureteral reconstruction
* History of nephrocalcinosis, medullary sponge kidney, cystinuria
* Immobility or relative immobility
* Planned staged ureteroscopy
* History of ureteral stent complication or poor tolerance or a ureteral stent
* Urinary tract infection or sepsis
* Current anticoagulation use (81 mg Aspirin permissible)
* NSAID contraindication (acute renal failure or chronic kidney disease, bleeding disorders, allergic reaction to NSAIDs, ulcer disease, auto-immune disease) DRUG: intra-nasal ketorolac, DRUG: oral diclofenac
Post Operative Pain, Urolithiasis, Ureter Calculi, Stent Complication, Kidney
UT Southwestern
Phase 2 Study of Combination Tivozanib and Nivolumab in Advanced Non-Clear Cell Renal Cell Carcinoma
To learn if giving tivozanib in combination with nivolumab can help to control advanced nccRCC.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years to old
PHASE2
NCT06053658
STU-2024-0577
Inclusion Criteria:
• Patients with histologically or cytologically confirmed metastatic non-clear cell renal cell carcinoma of papillary, chromophobe, oncocytic neoplasms, unclassified, or not otherwise specified (NOS) as clear cell. Medullary carcinoma of the kidney and collecting duct tumors are NOT allowed
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Up to 1 systemic line of therapy (either monotherapy or combination) including prior immunotherapy (anti-PD1, PD-L1, or CTLA-4) and multi-tyrosine kinase inhibitors in non-metastatic or metastatic setting is allowed. A washout period of 5 half lives or 21 days, whichever one is shorter, will be required for patients that have received previous systemic therapy.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) Appendix 1 performance status ≤2 (Karnofsky ≥60%).
• Patients must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥1,000/mcL
• platelets ≥100,000/mcL
• total bilirubin ≤ institutional upper limit of normal (ULN)
• AST ≤3 × institutional ULN
• (ALT) ≤3 × institutional ULN
• creatinine ≤1.5 × institutional ULN
• eGFR ≥30 ml/min
• 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.
• 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 treated brain metastases (at least 4 weeks have passed from treatment) are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression.
• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• The effects of combination tivozanib and nivolumab on the developing human fetus are unknown. For this reason and because tyrosine kinase inhibitors and immunotherapy agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential (WOCBP) and men 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. (refer to MDA Policy CLN 1114) This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months). * History of hysterectomy or bilateral salpingo-oophorectomy. * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). * History of bilateral tubal ligation or another surgical sterilization procedure. Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device, Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. 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 4 months after completion of combination tivozanib and nivolumab administration.
• Participants or their legally acceptable representative (LAR) must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
Exclusion Criteria:
• Prior tivozanib therapy.
• Prior nivolumab therapy.
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tivozanib or nivolumab.
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 100 mmHg on 2 or more antihypertensive medications, documented on 2 consecutive measurements taken at least 2 hours apart. Anti-hypertensives must not have been increased 30 days prior to enrollment.
• History of autoimmune disorders except for the following:
• Patients with vitiligo or alopecia
• Hypothyroidism (e.g. following Hashimoto syndrome) that is stable on thyroid hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active autoimmune disease requiring treatment in the last 3 years may be included after consultation with study MDA lead Principal Investigator
• Active human immunodeficiency virus (HIV) infection unless patients are on effective anti-retroviral therapy with undetectable viral load within 6 months.
• Has evidence of any other medical conditions, psychiatric condition, physical examination or laboratory findings that may interfere with the planned treatment, affect subject compliance or place the subject at high risk from treatment-related complications in the opinion of the local principal investigator (PI).
• Current systemic corticosteroid use greater than prednisone 10 mg daily or equivalent.
• Pregnant women are excluded from this study because tivozanib and nivolumab are agents with the 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 tivozanib and nivolumab, breastfeeding should be discontinued if the mother is treated with tivozanib and nivolumab.
• Receiving concomitant CYP3A inducers.
DRUG: Tivozanib, DRUG: Nivolumab
Renal Cell Carcinoma, Kidney
UT Southwestern
DIALYSIS-TIR Study
This study will look at control of blood sugar levels in persons with type 2 diabetes mellitus currently on chronic dialysis. Researchers will compare blood sugar levels in people taking semaglutide to people taking "dummy" medicine. The treatment participants get will be decided randomly. Participants will need to inject the study medication once a week. The study will last for 1 year and a month. Participants will be asked to wear a sensor that measures blood sugar levels for a period of 10 days at five different time points during the study.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Saubia.Mian@UTSouthwestern.edu
Ildiko Lingvay
ALL
18 Years and over
PHASE4
NCT06042153
STU-2022-0786
Inclusion Criteria:
• Ability to provide informed consent before any trial-related activities. Trial-related activities are any procedures that are carried out as a part of trial, including activities to determine suitability for the trial.
• Male or female Adults (age \> 18 years at the time of signing the consent)
• Type 2 diabetes mellitus diagnosed \> 6 months prior to screening
• On current chronic treatment with Hemodialysis or Peritoneal dialysis for \> 6 months prior to screening
• Current treatment with any glucose lowering pharmacotherapy, at a stable dose for at least 30 days. DPP-4 Inhibitors will be allowed at study entry and will be stopped at randomization.
• Minimum of 80% valid data on the 10-day Continuous Glucose Monitor download
• Time in Range 15 to 60%
Exclusion Criteria:
• BMI \< 23 kg/m2 at screening
• Current (within the past 90 days of screening) use of any GLP-1 RA
• Personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia type 2
• Known or suspected hypersensitivity to GLP-1 RA (trial medication(s), excipients, or related products)
• Pregnant, breast-feeding or the intention of becoming pregnant, or not using effective contraceptive measures
• Active weight loss, defined as weight loss of \>5% of body weight in the past 3 months
• Current participation in other interventional trials or last dose of any investigational product within 4 half- lives at the time of randomization
• Any medical condition which in the judgement of the investigator precludes safe participation in the trial (includes, but not limited to active neoplasm, severe heart failure, recent cardiovascular event, severe frailty, planned cardiac or vascular surgeries on the day of screening etc)
• If weight loss is not desired by the participant, or if the provider or investigator considers intentional weight loss to be detrimental to the health of the participant
• Other or secondary forms of diabetes (like type 1 diabetes, pancreatogenic diabetes mellitus, MODY, LADA, drug induced, etc.)
• Current diagnosis of gastroparesis or enteropathywhich in the opinion of investigator precludes safe treatment with GLP-1 RA.
• Hypoglycaemia unawareness, or history of frequent or severe hypoglycaemia (in the opinion of the investigator)
• Personal history of chronic pancreatitis, or acute pancreatitis within 180 days of screening
• Known current uncontrolled or unstable retinopathy (by medical history)
DRUG: Semaglutide, DRUG: Placebo
Type 2 Diabetes, End Stage Renal Disease on Dialysis
UT Southwestern
Effect of RBT-1 on Reducing the Risk of Post-Operative Complications in Subjects Undergoing Cardiac Surgery and Sub-Study of Clinical Protocol REN-007: A Population Pharmacokinetic (popPK) Evaluation of RBT-1
The purpose of this study is to evaluate the effect of RBT-1 on reducing the risk of post-operative complications in subjects undergoing cardiac surgery on cardiopulmonary bypass (CPB). Sub-study: To evaluate the pharmacokinetic (PK) profile of a single administration of RBT-1 (45 mg SnPP/240 mg FeS) by means of a popPK approach in subjects scheduled to undergo cardiac surgery
Call 214-648-5005
studyfinder@utsouthwestern.edu, Kristen.Matlock@UTSouthwestern.edu
Michael Jessen
All
18 Years and over
Phase 3
NCT06021457
STU-2023-0650
Inclusion Criteria:
• Male or female, ≥18 years of age at Screening.
• Planned to undergo non-emergent CABG and/or cardiac valve surgery requiring CPB; non-emergent surgery must allow for study drug infusion ≥24 but ≤48 hours prior to surgery.
• If female, subjects must use an effective method of birth control or abstain from sexual relations with a male partner (unless has undergone tubal ligation or hysterectomy or is at least 1 year postmenopausal) for the duration of their study participation.
• If male, subjects must use an effective method of birth control or abstain from sexual relations with a female partner for the duration of their study participation, unless the subject has had a vasectomy ≥6 months prior to infusion with study drug.
• Willingness to comply with all study-related procedures and assessments.
Exclusion Criteria:
• Surgery planned to occur <24 hours from the start of study drug infusion.
• Presence of acute organ dysfunction (AKI, acute decompensated heart failure, acute respiratory failure, stroke, etc) as assessed by the Investigator at the time of Screening.
• Surgery to be performed without CPB.
• Chronic kidney disease (CKD) requiring dialysis.
• Hypokalemia and/or hypomagnesemia within 24 hours prior to study drug infusion; electrolytes can be replenished if low.
• Cardiogenic shock or requirement for inotropes, vasopressors, or other mechanical devices, such as intra-aortic balloon pump (IABP).
• Known history of cancer within the past 2 years, except for carcinoma in situ of the cervix or breast, early-stage prostate cancer, or adequately treated non-melanoma cancer of the skin.
• Known or suspected sepsis at time of Screening.
• Asplenia (anatomic or functional).
• History of hemochromatosis, iron overload, or porphyria.
• Known hypersensitivity or previous anaphylaxis to SnPP or FeS.
• Female subject who is pregnant or breastfeeding.
• Participation in a study involving an investigational drug or device within 30 days prior to study drug infusion.
• In the opinion of the Investigator, for any reason, the subject is an unsuitable candidate to receive RBT-1.
Drug: RBT-1, Drug: Placebo
Post-Operative Complications in Cardiac Surgery, Heart, Kidney
Cardiac Surgery, CABG, Valve, Cardiopulmonary Bypass, Preconditioning
UT Southwestern
KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors (FIT-001)
This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess KO-2806, a farnesyl transferase inhibitor (FTI), as a monotherapy and in combination, in adult patients with advanced solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years to old
PHASE1
NCT06026410
STU-2024-1021
Inclusion Criteria:
* At least 18 years of age.
* Histologically or cytologically confirmed advanced solid tumors
* Arm #1 (Monotherapy): HRAS-mutant and/or amplified tumors (any solid tumor type); HRAS overexpression (only for HNSCC tumors); KRAS and/or NRAS, and/or HRAS-mutant and/or amplified NSCLC or CRC; KRAS-mutant and/or amplified PDAC
* Arm #2 (Combination): Must have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC
* Arm #3 (Combination): Must have KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC and have received at least 1 prior systemic therapy for advanced or metastatic disease
* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
* Karnofsky Performance Status of 70 or higher with no clinically significant deterioration over the previous 2 weeks.
* Acceptable liver, renal, endocrine, and hematologic function.
* Other protocol-defined inclusion criteria may apply.
Exclusion Criteria:
* Ongoing treatment with certain anticancer agents.
* Prior treatment with an FTI or HRAS inhibitor.
* Major surgery, other than local procedures, within 28 days prior to Cycle 1 Day 1, without complete recovery.
* Spinal cord compression, leptomeningeal disease, or clinically active CNS metastases.
* Toxicity (excluding alopecia) from prior therapy that has not been completely resolved to baseline at the time of consent.
* Active or prior documented autoimmune or inflammatory disorders within the past 5 years prior to Cycle 1 Day 1 (with exceptions).
* Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.
* Inability to swallow, impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs.
* Inadequate cardiac and/or vascular function, including receipt of treatment for unstable angina, myocardial infarction, and/or cerebro-vascular attack within the prior 6 months, mean QTcF ≥470 ms, or Class II or greater congestive heart failure.
* Other invasive malignancy within 2 years.
* Other protocol-defined exclusion criteria may apply. DRUG: KO-2806, DRUG: Cabozantinib, DRUG: Adagrasib
Solid Tumors With HRAS Alterations, Non Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Clear Cell Renal Cell Carcinoma (ccRCC), Renal Cell Carcinoma (Kidney Cancer), Colon, Kidney, Lung/Thoracic, Pancreas
HRAS, KRAS, NRAS, Farnesyl transferase inhibitor (FTI), Tyrosine Kinase inhibitor (TKI), Phase 1, KRAS G12C inhibitor, NSCLC, ccRCC, RCC, PDAC, CRC
UT Southwestern
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
ALL
18 Years and over
PHASE1
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
Triple Negative Breast Cancer, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Lymphoma, Non-Hodgkin, Mantle Cell Lymphoma, Bladder Cancer, Uveal Melanoma, Recurrent, Cervix Cancer, Carcinoma In Situ, Head and Neck Squamous Cell Carcinoma, Skin Cancer, Metastatic Cancer, Tumor, Solid, Tumor Recurrence, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Lung/Thoracic, Lymphoid Leukemia, Melanoma, skin, Multiple Myeloma, Mycosis Fungoides, Non-Hodgkins Lymphoma, Other Digestive Organ, Other Endocrine System, Other Skin, Rectum, Small Intestine, Soft Tissue, Stomach, Urinary Bladder
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, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
This phase II/III trial examines whether patients who have undergone surgical removal of bladder, kidney, ureter or urethra, but require an additional treatment called immunotherapy to help prevent their urinary tract (urothelial) 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 urothelial cancer patients who have undergone surgical removal of their bladder, kidney, ureter or urethra.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE2
NCT05987241
STU-2024-0089
Inclusion Criteria:
* PRE-REGISTRATION: Histologically confirmed muscle-invasive urothelial carcinoma of the urethra, bladder, ureter or renal pelvis
* PRE-REGISTRATION: Variant histology, including neuroendocrine differentiation, sarcomatoid, micropapillary, glandular, trophoblastic, Mullerian, 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 surgery (i.e., cystectomy and lymph node dissection or nephroureterectomy or ureterectomy) ≥ 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 radical cystectomy or nephroureterectomy or ureterectomy (imaging is not required prior to pre-registration but is required prior to registration)
* PRE-REGISTRATION: Have undergone a radical cystectomy nephroureterectomy, or ureterectomy with pathological evidence of urothelial carcinoma 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 systemic therapy: pT3-pT4\* or pT0/x-pT4/N+ on radical surgery (i.e., cystectomy, nephroureterectomy, or ureterectomy) 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 adjuvant cisplatin-based 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 radical surgery specimen (without prior neoadjuvant systemic therapy) with ctDNA(+) Signatera results based on an assay performed post-radical surgery 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 neoadjuvant systemic therapy: ypT2-T4a and/or ypN+ on radical surgery (i.e., cystectomy. , nephroureterectomy, or ureterectomy) pathology specimen. Neoadjuvant systemic therapy may have included cisplatin-based chemotherapy, cisplatin-based chemotherapy plus PD-1/PD-L1 blockade, or enfortumab vedotin plus PD-1/PD-L1 blockade
* PRE-REGISTRATION: Available tumor tissue for central Signatera testing to be submitted at 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 local 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 radical surgery specimen is preferred over tissue from prior diagnostic biopsy specimen (e.g., transurethral resection of bladder tumor specimen)
* 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 radical surgery
* PRE-REGISTRATION: No adjuvant radiation after radical surgery
* 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 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 grade ≥ 3 immune related adverse event with prior PD-1/PD-L1 blockade
* 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 or nephroureterectomy or ureterectomy =\< 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 at 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 or nephroureterectomy or ureterectomy 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
* REGISTRATION: No change since registration in clinical condition and/or laboratory tests that would impact the safety of nivolumab +/- relatlimab administration in the opinion of the treating investigator
* 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 administration 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 to site (not from the date sample was drawn). PROCEDURE: Biospecimen Collection, OTHER: cfDNA or ctDNA Measurement, PROCEDURE: Computed Tomography, PROCEDURE: Cystoscopy, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, OTHER: Questionnaire Administration, BIOLOGICAL: Relatlimab
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma, Muscle Invasive Ureter Urothelial Carcinoma, Muscle Invasive Urethral Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage IV Bladder Urothelial Carcinoma AJCC v7, Urinary Bladder
UT Southwestern
EffCaMgCit to Prevent Mineral Metabolism and Renal Complications of Chronic PPI Therapy
Proton pump inhibitors (PPIs) are widely used for the control of gastric ulcer-gastritis, erosive esophagitis (gastroesophageal reflux disease), peptic ulcer disease (duodenal ulcer), and heartburn. Despite their efficacy, their use has been implicated in possibly causing fragility fractures (osteoporosis), hypomagnesemia (magnesium deficiency) and increased risk of chronic kidney disease (CKD). The current trial represents the investigators ongoing effort to discern whether these complications could be averted by effervescent calcium magnesium citrate (EffCaMgCit).
Call 214-648-5005
studyfinder@utsouthwestern.edu, Alice.Osuji@UTSouthwestern.edu
Khashayar Sakhaee
ALL
21 Years to 99 Years old
PHASE3
NCT05998863
STU-2023-0340
Inclusion Criteria:
* Ambulatory adult subjects (\> 21 years of age) of either gender of any ethnicity
* Must have taken PPI (omeprazole or equivalent ≥ 20 mg/day, ≥ three times per week, for at least 2 months)
* Expected to continue at a similar dosage
* Stage 1 hypertension (with systolic blood pressure \<140 and diastolic \<90)
* Controlled diabetes mellitus Type II with HbA1C less than 7%
Exclusion Criteria:
* End-stage renal failure on dialysis
* Hypercalcemia,
* Hypophosphatemia (serum P \< 2.5 mg/dL)
* Hypertension stage 2 or higher
* Diabetes Type II with HbA1C ≥ 7%
* Treatment with adrenocorticosteroids, diuretics, non-steroidal anti-inflammatory agents - - Regular dose of magnesium supplements, bisphosphonate, teriparatide, denosumab or selective estrogen receptor modulators
* Required to take calcium
Inclusion/exclusion of other drugs or conditions will be considered on an individual basis. DRUG: EffCaMgCit, OTHER: Placebo
Osteoporosis, Hypomagnesemia, Other Digestive Organ
Bone mineral density
UT Southwestern
Sequential Treatment of Cabozantinib for Advanced Renal Cell Carcinoma (RCC)
The goal of this clinical trial is to learn about the effects of a higher dose of ncabozantinib in patients with advanced renal cell carcinoma who have progressed on or after receiving cabozantinib treatment.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE2
NCT05931393
STU-2023-0439
Inclusion Criteria:
• Patients with advanced RCC (defined as locally advanced unresectable or metastatic) of any histology who progressed on/after cabozantinib monotherapy in any line of treatment. Patient must have cabozantinib sensitive disease (prior treatment with cabozantinib ≥ 6 months)
• Ability to tolerate prior cabozantinib at 60mg PO daily with manageable toxicity profile at the respective doses, at investigator discretion
• Prior PD-1 inhibitor/PD-L1 inhibitor allowed
• Evidence of measurable disease per RECIST 1.1
• For up to 5 patients opting into on-treatment biopsy, one of the following must be met:
• Archival tissue confirmed to be available and obtained within 30 days of informed consent as well as willingness to undergo an on-treatment biopsy at 12 weeks (+/- 7 days). OR
• Willingness to undergo a baseline biopsy prior to Cycle 1 Day1, as well as an on-treatment biopsy at 12 weeks (+/- 7 days).
• Age ≥ 18 at time of consent
• ECOG performance status ≤ 2
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
• No washout period is needed for cabozantinib, minimum of 4 weeks or 4 half-lives washout, whichever is shorter, for other standard or experimental anti-cancer therapies.
• Recovery to baseline or ≤ Grade 1 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
• Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1500/µL without granulocyte colony-stimulating factor (G-CSF) support
• White blood cell (WBC) count ≥ 2500/µL
• Platelets ≥ 100,000/µL without transfusion
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L) (transfusion acceptable per investigator discretion)
• Alanine transaminase (ALT), AST and alkaline phosphatase (ALP) ≤ 3 x ULN. ALP ≤ 5x ULN with documented bone metastases
• Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3x ULN)
• Serum albumin ≥ 2.8 g/dl
• Prothrombin (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test \< 1.3x the laboratory ULN
• Serum creatinine ≤ 1.5x ULN or calculated creatinine clearance ≥ 40mL/min (≥ 0.675mL/sec) using the Cockcroft-Gault equation: * Males: (140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72) * Females: \[(140 - age) x weight (kg)/(serum creatinine \[mg/dL\] × 72)\] × 0.85
• Urine protein/creatinine ratio (UPCR) ≤1 mg/mg (≤113.2 mg/mmol), or 24h urine protein ≤1 g
• Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of cabozantinib Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Female subjects are considered to be of childbearing potential unless one of the following criteria is met: * documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy), or * documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes.
• In addition, females \< 55 years-of-age must have a serum follicle stimulating hormone (FSH) level \> 40 mIU/mL to confirm menopause.
Exclusion Criteria:
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for 1) at least 2 weeks after radiotherapy or 2) at least 4 weeks after major surgery (e.g., removal or biopsy of brain metastasis) prior to first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment for the brain metastasis at the time of first dose of study treatment
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following: 1) prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH). 2) Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders: 1) congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias; 2) uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment within 1 week of treatment; 3) stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis \[DVT\], pulmonary embolism \[PE\]) within 6 months before first dose of study treatment. Note: subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with a stable dose of permitted anticoagulation (see exclusion criterion #3.2.4) for at least 1 week before first dose of study treatment
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation, including 1) the subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction; 2) abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose of study treatment. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment
• Clinically significant hematuria, hematemesis, hemoptysis, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 6 weeks before first dose of study treatment. (Clinically significant hematuria defined by needing transfusion; clinically significant hematemesis or hemoptysis defined by needing hospital admission)
• Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation. Cavitary pulmonary lesions are allowed if not symptomatic.
• Lesions invading or encasing any major blood vessels
• Other clinically significant disorders that would preclude safe study participation
• Serious non-healing wound/ulcer/bone fracture
• Moderate to severe hepatic impairment (Child-Pugh B or C).
• Acute COVID-19 infection - clinical recovery from COVID-19 infection at least 14 days prior to enrollment allowed.
• Major surgery (e.g., laparoscopic nephrectomy, GI surgery, removal or biopsy of brain metastasis) within 2 weeks before first dose of study treatment. Minor surgeries within 10 days before first dose of study treatment. Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
• Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms per electrocardiogram (ECG) within 14 days before first dose of study treatment. Furthermore, subjects with a history of additional risk factors for torsades de pointes (e.g., long QT syndrome) are also excluded. Note: If a single ECG shows a QTcF with an absolute value \> 500 ms, two additional ECGs at intervals of approximately 3 min must be performed within 30 min after the initial ECG, and the average of these three consecutive results for QTcF will be used to determine eligibility.
• Pregnant or lactating females
• Inability to swallow tablets
• Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded
• Another malignancy within 2 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, Gleason 6 prostate cancer, or carcinoma in situ of cervix or breast
DRUG: Cabozantinib 80 MG
RCC, Renal Cell Carcinoma, Kidney
UT Southwestern
A Safety and Efficacy Study of HCB101, Fc-fusion Protein Targeting SIRPα-CD47 Pathway, in Solid or Hematological Tumors
The purpose of this study is to find out whether IV injection of HCB101 is an effective treatment for different types of advanced solid tumors or relapsed and refractory non-Hodgkin lymphoma and what side effects (unwanted effects) may occur in subjects aged 18 years old and above.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
All
18 Years and over
Phase 1
NCT05892718
STU-2023-1031
Inclusion Criteria:
• Able to understand and willing to sign the ICF.
• Male and female subjects of ≥18 years of age.
• Histologically/cytologically confirmed, locally advanced solid tumor: subjects with histologically or cytologically confirmed advanced solid tumors refractory to standard therapy, or for which no standard treatment exists or non-Hodgkin lymphoma, relapsed or refractory to at least 2 prior lines of therapy.
• For subjects with advanced solid tumor - must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline.
• For subjects with non-Hodgkin lymphoma - must have non-Hodgkin lymphoma that is measurable or assessable for response per Lugano Classification (with 2016 refinement).
• Must have ECOG performance status of 0 to 2 at Screening.
• Able to provide tumor tissue samples.
• Have life expectancy of ≥12 weeks.
Exclusion Criteria:
• With known history of hypersensitivity to any components of HCB101.
• Known active or untreated CNS metastases and/or carcinomatous meningitis.
• Have undergone a major surgery or radical radiotherapy or palliative radiotherapy or have used a radioactive drug that is not completed at least 2 weeks prior to the first dose of HCB101.
• Clinically significant cardiovascular condition.
• Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia.
• With known inherited or acquired bleeding disorder or bleeding diathesis. .
• Have RBC transfusion within 4 weeks prior to Screening.
• With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
• Any investigational or approved systemic cancer therapy.
• Active use of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on case by case basis. There will be no restriction for daily aspirin ≤ 81 mg/QD.
• Have used herbal medication within 14 days prior to the first dose of HCB101.
• Have received any treatment targeting the CD47 or SIRPα pathway.
• Have other malignancies requiring treatment within 2 years prior to the first dose of HCB101.
• Participation in another clinical study with an investigational product administered in the last 14 days prior to receiving the first dose of HCB101.
• An investigational device used within 28 days prior to the first dose of HCB101.
• Positive for hepatitis B, active hepatitis C infections, positive for HIV, or known active or latent tuberculosis.
• Known to have a history of alcoholism or drug abuse.
Drug: HCB101
Advanced Solid Tumor, Refractory Non-Hodgkin Lymphoma, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkins Lymphoma, Kaposis sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung/Thoracic, Multiple Myeloma, Non-Hodgkins Lymphoma, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Stomach, Thyroid, Urinary Bladder
Immunotherapy, CD47, SIRPα, Solid Tumor, Lymphoma
UT Southwestern; Parkland Health & Hospital System
Mitoquinone/mitoquinol Mesylate As Oral and Safe Postexposure Prophylaxis for Covid-19
Adults who do not have major health, kidney, gastrointestinal disease will be randomized to receive oral mitoquinone/mitoquinol mesylate (Mito-MES) versus placebo to prevent the development and progression of COVID-19 after high-risk exposure to a person with confirmed SARS-CoV-2 infection.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Theodoros.Kelesidis@UTSouthwestern.edu
Theodoros Kelesidis
ALL
18 Years to 65 Years old
PHASE2
NCT05886816
STU-2023-0524
Inclusion Criteria:
Age 18-65 years old Asymptomatic (no symptoms of viral infection) on study entry High risk exposure without use of masks to confirmed case of COVID-19 Members in a household one of which is a confirmed case of COVID-19 Negative baseline SARS-COV-2 diagnostic test
Exclusion Criteria:
* Women with variations in physiological functions due to hormones that may effect immune function and (transgender, pregnant, breastfeeding)
* Specific significant clinical diseases \[cardiovascular disease (such as coronary artery/vascular disease), heart disease (such as congestive heart failure, cardiomyopathy, atrial fibrillation), lung disease (such as chronic obstructive pulmonary disease, asthma, bronchiectasis, pulmonary fibrosis, pleural effusions), kidney disease (glomerular filtration rate or GFR less than 60 ml/min/1.73 m2), liver disease (such as cirrhosis, hepatitis), major immunosuppression (such as history of transplantation, uncontrolled HIV infection, cancer on active chemotherapy\] based on history. Participants with well controlled HIV (CD4 count \> 500 cells/mm\^3 and HIV viral load \< 50 copies/ml) and people with remote history of cancer not on active treatment will be allowed to participate.
* History of known gastrointestinal disease (such as gastroparesis) that may predispose patients to nausea
* History of auto-immune diseases
* Chronic viral hepatitis
* Use of systemic immunomodulatory medications (e.g. steroids) within 4 weeks of enrollment
* Any participant who has received any investigational drug within 30 days of dosing
* History of underlying cardiac arrhythmia
* History of severe recent cardiac or pulmonary event
* A history of a hypersensitivity reaction to any components of the study drug or structurally similar compounds including Coenzyme Q10 and idebenone
* Unable to swallow tablets
* Use of any investigational products within 4 weeks of enrollment
* Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements.
* Eligible for other FDA approved treatment for post-exposure prophylaxis against SARS-CoV-2
* Use of Coenzyme Q10 or Vitamin E \< 120 days from enrollment DRUG: Mitoquinone/mitoquinol mesylate, OTHER: Placebo
SARS-CoV Infection, COVID-19, Lung/Thoracic, Nose
SARS-CoV Infection, COVID-19, Post-exposure prophylaxis
UT Southwestern; Parkland Health & Hospital System
Study of JANX008 in Subjects with Advanced or Metastatic Solid Tumor Malignancies
This study is a first-in-human (FIH), Phase 1/1b, open-label, multicenter dose escalation and dose expansion study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of JANX008 in adult subjects with advanced or metastatic carcinoma expressing EGFR.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years to 100 Years old
PHASE1
NCT05783622
STU-2023-0808
Inclusion Criteria:
* Subjects ≥18 years of age at the time of signing informed consent
* Histologically or cytologically documented locally advanced or metastatic NSCLC, SCCHN, CRC, RCC, SCLC, PDAC, TNBC
* Progressed or was intolerant to all available therapies known to confer clinical benefit appropriate for the tumor type
* Adequate organ function
* At least 1 measurable lesion per RECIST 1.1
Exclusion Criteria:
* Treatment with anti-cancer therapy within 28 days or ≤5 elimination half-lives, whichever is earlier, before enrollment
* Prior treatment with EGFR-targeted bispecific T cell engager or CAR-T cell therapy
* Prior treatment with CD3 engaging bispecific antibodies
* Clinically significant cardiovascular diseases
* Active clinically significant infection (bacterial, viral, fungal, mycobacteria, or other)
* On supplemental oxygen
* Any medical condition or clinical laboratory abnormality likely to interfere with assessment of safety or efficacy of study treatment DRUG: JANX008
Non-Small Cell Lung Cancer, Renal Cell Carcinoma, Squamous Cell Carcinoma of the Head and Neck, Colorectal Carcinoma, Small Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma, Triple-Negative Breast Cancer, Colon, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Lung/Thoracic, Rectum
UT Southwestern
ARTEMIS: Ravulizumab to Protect Patients With CKD From CSA-AKI and MAKE (ARTEMIS)
The primary objective of this study is to assess the efficacy of a single dose of ravulizumab IV compared with placebo in reducing the risk of the clinical consequences of AKI (MAKE) at 90 days in adult participants with CKD who undergo non-emergent cardiac surgery with CPB.
Call 214-648-5005
studyfinder@utsouthwestern.edu, salina.shrestha@utsouthwestern.edu
Michael Jessen
All
18 Years to 90 Years old
Phase 3
NCT05746559
STU-2023-0186
Inclusion Criteria:
• Participant weighs ≥ 30 kg
• Planned non-emergent sternotomy with CPB procedure for the following surgeries:
• Multi-vessel CABG
• Valve replacement or repair; ascending aorta surgery permitted if combined with aortic valve replacement/repair
• Combined CABG and valve surgery; inclusion of single-vessel CABG when combined with valve replacement/repair is permitted
• Known CKD for at least 90 days (CKD Stage 3A, 3B, or 4)
Exclusion Criteria:
• Emergency or salvage cardiac surgery is expected at screening or randomization, as assessed by the Investigator.
• Single-vessel CABG without valve surgery is planned.
• Off-pump surgery is planned (eg, surgery without CPB).
• Recipient of a solid organ or bone marrow transplantation.
• Cardiogenic shock, hemodynamic instability, use of intra-aortic balloon pump, extracorporeal membrane oxygenation, or left ventricular assist device within 72 hours of randomization.
• Active systemic bacterial, viral, or fungal infection within 14 days prior to randomization.
• History of unexplained, recurrent infection.
• Any use of KRT or presence of AKI within 30 days of randomization
• Use of any complement inhibitors, or plasmapheresis or plasma exchange within the year prior to Screening, or planned use during the course of the study.
• Participant is not willing to be vaccinated against N meningitidis or is unwilling to receive prophylactic treatment with appropriate antibiotics, if needed
• History of or unresolved N meningitidis infection.
Drug: Placebo, Drug: Ravulizumab
Chronic Kidney Disease, CKD, Cardiac Disease, Cardiopulmonary Bypass, Kidney
Chronic Kidney Disease, CKD, Cardiac Disease, cardiopulmonary bypass
UT Southwestern
Neutrophil and Monocyte Deactivation Via the SeLective CytopheretIc Device - a Randomized Clinical Trial in Acute Kidney Injury (NEUTRALIZE-AKI)
This randomized, controlled, pivotal study is intended to determine whether up to ten sequential 24-hour treatments with the Selective Cytopheretic Device (SCD) will improve survival in patients with Acute Kidney Injury (AKI) requiring continuous kidney replacement therapy (CKRT) when compared to CKRT alone (standard of care). This study is further intended to determine whether SCD therapy will reduce the duration of maintenance dialysis secondary to AKI. This study will enroll approximately 200 subjects across 30 US sites. Participants will be patients in an intensive care unit (ICU) setting with a diagnosis of AKI requiring CKRT.
Call 214-648-5005
studyfinder@utsouthwestern.edu, Jessica.Williams@UTSouthwestern.edu
Tamim Hamdi
ALL
18 Years and over
NA
NCT05758077
STU-2024-0432
Inclusion Criteria:
* Admitted to an ICU requiring CKRT:
• Must have AKI stage 2 or greater at the time of CKRT initiation.
• Must have been on CKRT for at least 12 hours but no greater than 48 hours at the time of enrollment. * At least 18 years of age but not older than 80 at the time of enrollment. * One additional life-threatening organ dysfunction present. * Acceptable vascular access for CKRT to include adequate lumen size and length of catheters. * Initial (non-binding) commitment to maintaining current level of care for at least 96 hours. * C-Reactive Protein \>3.5 mg/dl.
Exclusion Criteria:
* Not expected to survive next 24 hours.
* Anticipated transition to comfort measures or hospice in next 4 days.
* Terminal condition whereby the patient is not expected to survive 28 days or any condition in which therapy is regarded as futile by the PI.
* Advanced malignancy which is actively being treated or may be treated with palliative chemotherapy or radiation.
* ICU hospitalization \> 14 days during this hospital admission (to include days spent at ICU of an outside hospital) at the time of screening.
* Active COVID-19 infection with a primary admission diagnosis of COVID-19.
* Chronic use of ventricular assist devices.
* ESRD requiring chronic kidney replacement therapy.
* History of CKD (greater than Stage 3).
* AKI stage 0 or stage 1 at the time of CKRT initiation.
* Non-ATN AKI diagnosis. We intend on relying on local nephrology subspecialty expertise to reasonably exclude non-ATN diagnoses based on clinical suspicions combined with prespecified objective criteria. If there is a reasonable suspicion that the subject has non-ATN AKI based on this, they will be excluded from the trial.
* Acute coronary syndromes, acute stroke, or acute major vascular compromise requiring medical or surgical interventions within 48 hours of randomization.
* Active hemorrhage requiring blood transfusions at the time of screening.
* Acute on Chronic Liver Failure.
* Suspicion of hepato-renal syndrome.
* Presence of any solid organ transplant at any time prior to admission.
* Severe burns with a modified Baux score \> 100 (%TBSA+Age+17 for Inhalation Injury).
* Bone marrow transplant within the last year.
* Chronic immunosuppression with an average of \>20 mg/day of prednisone or other steroid sparing immunosuppressants for the past 30 days prior to hospital admission.
* Individuals who have a history of primary or secondary immune disorders including, but not limited to, HIV or AIDS.
* Dry weight of \>150kg.
* Platelet count \<15,000/mm3.
* Patient is a prisoner or member of a vulnerable population.
* Patient is pregnant or breast feeding.
* Concurrent enrollment in another interventional clinical trial for an investigational drug or device.
* Need for plasmapheresis. DEVICE: Selective Cytopheretic Device, OTHER: Standard of Care
Acute Kidney Injury
continuous kidney replacement therapy, continuous renal replacement therapy, acute kidney injury, organ failure, inflammation, dialysis, acute tubular necrosis
UT Southwestern
FORAGER-1: A Study of LOXO-435 (LY3866288) in Participants With Cancer With a Change in a Gene Called FGFR3 (FORAGER-1)
The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-435 by itself or when it is combined with other standard medicines that treat cancer. 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
ALL
18 Years and over
PHASE1
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: Presence of an alteration in FGFR3 or its ligands
* Cohort A2, B2, B3, and B5: Histological diagnosis of urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
* Cohorts B1 and B4: Histological diagnosis of urothelial cancer that is locally advanced or metastatic
* Cohort C1: Must have histological diagnosis of a non-urothelial solid tumor malignancy that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration
* Measurability of disease:
* Cohort A1 and B3: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1)
* Cohorts A2, B1, B2, B4, B5, and C1: Measurable disease required as defined by RECIST v1.1
* Have adequate tumor tissue sample available. Participants with inadequate tissue sample availability may still be considered for enrollment upon review
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 for Cohorts A1, A2, B3, and B5
* Less than or equal to 2 for Cohorts B1, B2, B4, and C1
* 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, B2, B3 participants must have received at least one prior regimen, and cohorts B1 and B4 participants at least 2 prior regimens, in the locally advanced or metastatic setting
* There is no restriction on number of prior therapies
* Cohort B5: Participants have not received prior systemic therapy for locally advanced or metastatic UC
* FGFR inhibitor specific requirements:
* Cohort A1/A2/B3: Prior FGFR inhibitor treatment is permitted but not required
* Cohort B1/B4: Participants must have been previously treated with erdafitinib
* Cohort B2, B5, and C1: Participants must be FGFR inhibitor naïve
Exclusion Criteria:
* Participants with primary central nervous system (CNS) malignancy
* Untreated or uncontrolled CNS metastases
* Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible
* 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, DRUG: enfortumab vedotin
Urinary Bladder Neoplasms, Neoplasm Metastasis, Ureteral Neoplasms, Anus, Bones and Joints, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kaposis sarcoma, 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, Small Intestine, Soft Tissue, Stomach, Thyroid, Unknown Sites, Urinary Bladder
Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer, Ureter Cancer
UT Southwestern; Parkland Health & Hospital System
Dose Escalation and Expansion Study of WTX-124 as Monotherapy and in Combination With Pembrolizumab (Pembro) in Patients With Selected Advanced or Metastatic Solid Tumors
A first-in-human, Phase I, open-label, multicenter study of WTX-124 administered as monotherapy and in combination with pembrolizumab to patients with advanced or metastatic solid tumors.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Hans Hammers
ALL
18 Years to old
PHASE1
NCT05479812
STU20250072
Inclusion Criteria:
Each patient must meet all the following criteria to participate in the study:
• Has histological or cytological documentation of a solid tumor indication for which a CPI (e.g. anti-PD-(L)1 is indicated for all parts of the clinical study;
• Monotherapy Dose Escalation: Patients with relapsed/refractory locally advanced or metastatic solid tumors for which immunotherapy is approved, who have progressed on or are intolerant to standard therapy, including CPIs, or for whom no standard therapy with proven benefit exists. Combination Dose Escalation: Patients with relapsed/refractory locally advanced or metastatic solid tumors for which immunotherapy is approved, who have progressed on or are intolerant to standard therapy or for whom no standard therapy with proven benefit exists. Monotherapy Dose Expansion: * Arm A: Patients with relapsed advanced or metastatic RCC who have received no more than 4 prior lines of therapy in the advanced or metastatic setting * Arm B: Patients with relapsed advanced or metastatic cutaneous malignant melanoma who have received no more than 2 prior lines of therapy for BRAF V600 wild type and no more than 3 prior lines of therapy for BRAF V600 mutant melanoma. * Arm C: Patients with relapsed advanced or metastatic cSCC who have received no more than 1 prior line of therapy Combination Dose Expansion:
• Arm D: Patients with RCC who have received no more than 3 prior lines of therapy
• Arm E: Patients with cutaneous melanoma who may be naïve to all prior therapy for advanced or metastatic disease. For BRAF wild type melanoma, patients should have received no more than 2 prior lines of therapy. For BRAF V600 mutant disease, patients should have received no more than 3 prior lines of therapy.
• Arm F: Patients with PD-L1-positive NSCLC who have received no more than 3 prior lines;
• ≥18 years of age;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• Has at least 1 measurable lesion per RECIST 1.1(lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions);
• Agrees to undergo a pre-treatment and on-treatment biopsy of a primary or metastatic solid tumor lesion;
• Has adequate organ and bone marrow function;
• Willingness of men and women of reproductive potential to observe highly effective birth control for the duration of treatment and for 4 months following the last dose of study drug;
• Additional criteria may apply
Exclusion Criteria:
• Have a history of another active malignancy (a second cancer) within the previous 2 years except for localized cancers that are not related to the current cancer being treated, are considered cured, and, in the opinion of the Investigator, presents a low risk of recurrence. These exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast;
• Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease;
• Have received prior IL-2-directed therapy;
• Have had an allogeneic tissue/solid organ transplant;
• Have known symptomatic brain metastases requiring steroids;
• Have significant cardiovascular disease;
• Have an active autoimmune disease that required systemic treatment in the past 2 years;
• Diagnosis of immunodeficiency, is on immunosuppressive therapy, or is receiving chronic systemic or enteric steroid therapy
• Major surgery (excluding placement of vascular access) within 2 weeks prior to the first dose of study drug;
• Investigational agent or anticancer therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to the first dose of study drug;
• Has received prior radiotherapy within 2 weeks of start of study treatment. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease;
• Any unresolved toxicities from prior therapy greater than NCI CTCAE version 5.0 Grade 1 at the time of starting study drug with the exception of alopecia and Grade 2 prior platinum-therapy related neuropathy;
• Received a live or live-attenuated vaccine within 30 days of the first dose of study drug; Note: Administration of killed vaccines or other formats are allowed.
• Active, uncontrolled systemic bacterial, viral, or fungal infection;
• HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease;
• Active infection as determined by hepatitis B surface antigen and hepatitis B core antibody, or hepatitis B virus DNA by quantitative polymerase chain reaction (qPCR) testing;
• Active infection as determined by hepatitis C virus (HCV) antibody or HCV RNA by qPCR testing;
• Pregnant or lactating;
• History of hypersensitivity to any of the study drug components;
• Additional criteria may apply.
DRUG: WTX-124, DRUG: pembrolizumab
Metastatic Solid Tumor, Advanced Solid Tumor, Kidney, Lung/Thoracic, Melanoma, skin
WTX-124, pembrolizumab, Tumors, Cutaneous Malignant Melanoma, mRCC, Renal Carcinoma, IL-2, Cutaneous SCC (cutaneous squamous cell carcinoma), NSCLC (non-small cell lung cancer)
UT Southwestern
Testing Cabozantinib With or Without Atezolizumab in Patients With Advanced Papillary Kidney Cancer, PAPMET2 Trial
This phase II trial compares the effect of atezolizumab in combination with usual treatment with cabozantinib to cabozantinib alone in patients with papillary renal cell carcinoma that has spread from where it first started (primary site) to other places in the body (metastatic). Papillary renal cell carcinoma (PRCC) is a type of kidney cancer that forms in the lining of the tiny tubes in the kidney that return filtered substances that the body needs back to the blood and remove extra fluid and waste as urine. Most papillary tumors look like long, thin finger-like growths under a microscope. It is also called papillary kidney cancer or PRCC. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the tumor and may interfere with the ability of tumor cells to grow and spread. Cabozantinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply and may also prevent the growth of new blood vessels that tumors need to grow. By these actions it may help slow or stop the spread of tumor cells. Combination therapy with atezolizumab and cabozantinib may shrink the tumor and allow a longer survival time in patients with metastatic renal cell carcinoma.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Suzanne Cole
ALL
18 Years and over
PHASE2
NCT05411081
STU-2023-0866
Inclusion Criteria:
* Participants must have a histologically confirmed diagnosis of metastatic papillary renal cell carcinoma (PRCC), either type 1 or type 2. (NOTE: A designation of type 1 or type 2 should be made by the local pathologist if possible but is not required). Mixed histologies which contain type 1 or type 2 along with any other RCC histology/histologies will be allowed provided that they contain a papillary component
* Participants must have measurable disease per RECIST 1.1 criteria. All measurable lesions must be assessed by CT or MRI within 28 days prior to registration. All non-measurable lesions must be assessed by CT or MRI, or nuclear medicine bone scan within 42 days prior to registration. The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. If there is clinical suspicion for bone metastases at the time of enrollment (at the discretion of the investigator), bone scan must be performed at baseline (within 42 days prior to registration)
* Participants with new or progressive brain metastases (active brain metastases) must not require immediate central nervous system (CNS) specific treatment at the time of study registration or anticipated during the first cycle of therapy. Patients with leptomeningeal disease are excluded from enrolling
* Participants with measurable disease, per RECIST version (v)1.1, must be present outside the CNS
* Participants must have no history of intracranial hemorrhage or spinal cord hemorrhage
* Participants must not have undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, or neurosurgical resection within 28 days prior to initiation of study treatment
* Participants must not have ongoing requirements for corticosteroids as therapy for CNS disease
* Participants, if needed, must receive a stable dose of anti-convulsant therapy
* Participants must not have cavitating pulmonary lesions
* Participants must not have uncontrolled pleural effusions, pericardial effusions, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Participants with indwelling catheters (e.g., PleurX \[registered trademark\]) are allowed
* Participants must not have tumor invading the gastrointestinal (GI) tract or evidence of endotracheal or endobronchial tumor within 28 days prior to registration
* Participants must not have evidence of tumor invading or encasing any major blood vessels
* Participants must not have had major surgery within 28 days prior to registration, and participants must have recovered from any adverse effects of surgery
* Participants must not have had prior treatment with cabozantinib for any reason
* Participants must not have had prior treatment or adjuvant therapy with PD-1/PD-L1 checkpoint inhibitors for any reason within the past 6 months
* Participants must not have received more than one prior systemic therapy for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor Food and Drug Administration (FDA)-approved for advanced RCC (i.e., pazopanib, bevacizumab, sorafenib or axitinib). If a participant develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic RCC. If a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC
* Participants must not take within 14 days prior to registration, nor plan to take while on protocol treatment, any strong CYP3A4 inhibitors (e.g. boceprevir, cobicistat, danoprevir, elvitegravir/RIT, fluvoxamine, indinavir, itraconazole, ketoconazole, lopinavir/RIT, nefazodone, nelfinavir, posaconazole, ritonavir, telaprevir, telithromycin, tipranavir/RIT, or voriconazole,); Please refer to https://drug-interactions.medicine.iu.edu/MainTable.aspx for the updated CYP3A4 inhibitors or inducers
* Participants must not take within 14 days prior to registration, nor plan to take while on protocol treatment, any strong CYP3A4 inducers (e.g. avasimibe, phenytoin, rifampin, rifabutin); Please refer to https://drug-interactions.medicine.iu.edu/MainTable.aspx for the updated CYP3A4 inhibitors or inducers
* Participants must complete all prior radiation therapy at least 14 days prior to registration. Participants must have recovered to =\< grade 1 from all associated toxicities at the time of registration unless the toxicity is determined to be not clinically significant by the registering investigator
* Participants must not be receiving or planning to receive any other investigational agents at time of registration
* Participants must not have been diagnosed with a clinically significant autoimmune disease, exceptions such as diabetes, eczema, and vitiligo are allowed. Other non-clinically significant autoimmune diseases are allowed if approved by the registering investigator
* Participants must not be on steroid doses \> 10 mg prednisone equivalent. Replacement steroid doses for adrenal insufficiency will be allowed. Also, short duration steroid therapy to prevent allergic reactions are acceptable (e.g. prior to CT imaging)
* Participants must be \>= 18 years of age
* Participants must have a complete physical examination and medical history within 28 days prior to registration
* Participants must have a Zubrod performance status of 0-2
* White blood count (WBC) \>= 2 x 10\^3/uL (within 28 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^3/uL (within 28 days prior to registration)
* Platelet count \>= 100 x 10\^3/uL (within 28 days prior to registration)
* Lymphocyte count \>= 0.5 x 10\^3/uL (within 28 days prior to registration)
* Hemoglobin (\>= 9 g/dL) (within 28 days prior to registration). Participants may be transfused to meet this criterion
* Total serum bilirubin =\< 1.5 x the institutional upper limit of normal (ULN) unless history of Gilbert's disease (within 28 days prior to registration). Participants with history of Gilbert's disease must have total bilirubin =\< 5 x institutional ULN
* Aspartate aminotransferase (AST) must be =\< 3 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGOT) must be =\< 5 x the institutional ULN (within 28 days prior to registration)
* Alanine aminotransferase (ALT), must be =\< 3 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGPT) must be =\< 5 x the institutional ULN (within 28 days prior to registration)
* Participants must have serum creatinine =\< 2 x the institutional ULN OR creatinine clearance (either measured or calculated) \> 30 mL/min and obtained within 28 days prior to registration
* Participants must not have any clinical evidence of congestive heart failure (CHF) (specifically, New York Heart Association \[NYHA\] class III \[moderate\] or class IV \[severe\]) at the time of registration
* Participants must not have known history of congenital long QT syndrome and must not have experienced unstable angina pectoris, clinically significant cardiac arrhythmias, or stroke (transient ischemic attack \[TIA\] or other ischemic event) within 90 days prior to registration
* Participants must not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 90 days of registration, unless clinically stable with ongoing medical management
* Participants must have urine protein \< 3+ within 28 days prior to registration. If urine protein is 3+ or greater, then urine protein by 24-hour collection must show less than 3 grams of protein
* Participants must have documented blood pressure of systolic blood pressure (SBP) \< 150 mm Hg or diastolic blood pressure (DBP) \< 100 mm Hg within 14 days prior to registration
* Participants with known human immunodeficiency virus (HIV) must be on effective anti-retroviral therapy at registration and have undetectable viral load within 6 months of registration
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy within 6 months prior to registration, if indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load within 6 months prior to registration
* Participants must be able to take oral medications (i.e., swallow pills whole). Participants must not have gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures that could in the opinion of the treating investigator affect absorption, or active peptic ulcer disease. Participants with intractable nausea or vomiting are not eligible
* Participants must not have had any clinically-significant GI bleeding within 3 months prior to registration and participants must not have a GI disorder which (at the discretion of the investigator) bears a high risk of perforation or fistula (e.g. Crohn's disease)
* Participants must not have had hemoptysis of \>= (2.5 mL) of red blood, and do not demonstrate any other signs indicative of pulmonary hemorrhage within 3 months prior registration
* Participants 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
* Participants must not be pregnant or nursing, due to VEGF therapy being toxic to embryogenesis. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must not be on warfarin, at therapeutic doses. Low dose aspirin for cardio-protection (per local applicable guidelines) and low molecular weight heparin (LMWH) are allowed
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
* NOTE: For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system BIOLOGICAL: Atezolizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabozantinib S-malate, PROCEDURE: Computed Tomography, PROCEDURE: Magnetic Resonance Imaging
Metastatic Papillary Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Kidney
UT Southwestern
Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study
This phase II trial tests whether using genetic testing of tumor tissue to select the optimal treatment regimen works in treating patients with clear cell renal cell (kidney) cancer that has spread to other places in the body (advanced or metastatic). The current Food and Drug Administration (FDA)-approved regimens for advanced kidney cancer fall into two categories. One treatment combination includes two immunotherapy drugs (nivolumab plus ipilimumab), which are delivered by separate intravenous infusions into a vein. The other combination is one immunotherapy drug (nivolumab infusion) plus an oral pill taken by mouth (cabozantinib). Nivolumab and ipilimumab are "immunotherapies" which release the brakes of the immune system, thus allowing the patient's own immune system to better kill cancer cells. Cabozantinib is a "targeted therapy" specifically designed to block certain biological mechanisms needed for growth of cancer cells. In kidney cancer, cabozantinib blocks a tumor's blood supply. The genetic (DNA) makeup of the tumor may affect how well it responds to therapy. Testing the makeup (genes) of the tumor, may help match a treatment (from one of the above two treatment options) to the specific cancer and increase the chance that the disease will respond to treatment. The purpose of this study is to learn if genetic testing of tumor tissue may help doctors select the optimal treatment regimen to which advanced kidney cancer is more likely to respond.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Tian Zhang
ALL
18 Years and over
PHASE2
NCT05361720
STU-2023-0365
Inclusion Criteria:
* Histological confirmation of RCC with a clear cell component
* Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \[AJCC\] stage IV) RCC
* Patient can comprehend and sign the study informed consent form
* Male or female \>= 18 years of age at the time of informed consent
* Karnofsky performance status (KPS) of \>= 70%
* No prior systemic therapy for RCC in the neoadjuvant, adjuvant or metastatic setting
* At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Tumor tissue for ribonucleic acid (RNA)-sequencing (tumor tissue from bony metastasis is not suitable but a soft tissue component around bone is acceptable)
* Screening tissue consent- Patient must be assigned to either Cluster 1/2 or 4/5. Patients assigned to cluster 3/6/7 will not be eligible for the treatment study
* Adequate renal function defined as calculated creatinine clearance \>= 30 mL/min per the Cockcroft and Gault formula
* Adequate liver function defined by:
* Total bilirubin =\< 1.5 times the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN
* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test during screening and prior to receiving first dose of protocol-indicated treatment
* Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal
* Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 years of age in the absence of other biological or physiological causes
Exclusion Criteria:
* =\< 14 days before first dose of protocol-indicated treatment:
* Major surgery requiring general anesthesia
* Inadequately controlled hypertension (systolic blood pressure \[SBP\] \> 160/90 mmHg)
* Anti-hypertensive medications are permitted.
* Active infection requiring infusional treatment
* Has preexisting gastrointestinal or non-gastrointestinal fistula
* Proteinuria \> 2 g/ 24 hours (hrs)
* If patient has 1+ protein on urine dipstick then a 24 hr urine collection is required
* Non-healing wounds on any part of the body (for patients assigned to Cabo/Nivo only)
* Known clinically significant active bleeding including hemoptysis
* Inability to swallow oral medication; or the presence of a poorly controlled gastrointestinal disorder that could significantly affect the absorption of oral study drug (for patients assigned to Cabo/Nivo only) - e.g., Crohn's disease, ulcerative colitis, chronic diarrhea (defined as \> 4 loose stools per day), malabsorption, or bowel obstruction
* Significant cardiovascular disease or condition including:
* Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) functional criteria
* Unstable angina pectoris (i.e., last episode =\< 3 months prior to first dose of protocol-indicated treatment)
* Myocardial infarction within 3 months prior to starting treatment
* Subjects with central nervous system (CNS) metastases are eligible after they have completed local therapy (e.g., whole brain radiation therapy \[WBRT\], surgery or radiosurgery)
* Any condition requiring systemic treatment with either systemic corticosteroids (\> 10 mg/day prednisone or equivalent daily) or other immunosuppressive medications within 14 days prior to initiating protocol-indicated treatment
* In the absence of active autoimmune disease: Subjects are permitted the use of corticosteroids with minimal systemic absorption (e.g., topical, ocular, intra-articular, intranasal, and inhalational), =\< 10 mg/day prednisone or equivalent daily; and physiologic replacement doses of systemic corticosteroids =\< 10 mg/day prednisone or equivalent daily (e.g., hormone replacement therapy needed in patients with hypophysitis) DRUG: Cabozantinib, BIOLOGICAL: Ipilimumab, BIOLOGICAL: Nivolumab
Advanced Clear Cell Renal Cell Carcinoma, Metastatic Clear Cell Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Kidney
UT Southwestern
Testing the Addition of Stereotactic Radiation Therapy With Immune Therapy for the Treatment of Patients With Unresectable or Metastatic Renal Cell Cancer, SAMURAI Trial (SAMURAI)
This phase II trial tests whether the addition of radiation to the primary tumor, typically given with stereotactic ablative radiation therapy (SABR), in combination with standard of care immunotherapy improves outcomes in patients with renal cell cancer that is not recommended for surgery and has spread from where it first started (primary site) to other places in the body (metastatic). Radiation therapy uses high energy photons to kill tumor cells and shrink tumors. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses of radiation over a shorter period and cause less damage to normal tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, ipilimumab, avelumab, and pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are in a class of medications called antiangiogenic agents. They work by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving SABR in combination with standard of care immunotherapy may help shrink or stabilize the cancer in patients with renal cell cancer.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Raquibul Hannan
ALL
18 Years and over
PHASE2
NCT05327686
STU-2023-0448
Inclusion Criteria:
* Pathologically (histologically or cytologically) proven diagnosis of renal cell carcinoma prior to registration
* Node-positive unresectable (TxN1Mx) or metastatic (TxNxM1) based on the following diagnostic workup:
* History/physical examination within 45 days prior to registration
* CT/magnetic resonance imaging (MRI) of the chest/abdomen/pelvis within 45 days prior to registration
* Patients must have IMDC intermediate (1-2 factors) or poor risk disease (\>= 3 factors)
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with measurable disease (node positive or metastatic) as defined by RECIST version 1.1 excluding the primary renal tumor
* Patient not recommended for or refused immediate cytoreductive nephrectomy
* Candidate for standard of care therapy with either immuno-oncology (IO)-IO or IO-VEGF combination regimen
* Primary renal tumor measuring 20 cm or less in anterior to posterior dimension only on axial imaging
* Age \>= 18
* Karnofsky performance status \>= 60 within 45 days prior to registration
* Hemoglobin \>= 8 g/dL (transfusions are allowed) (within 45 days prior to registration)
* Platelet count \>= 50,000/mm\^3 (within 45 days prior to registration)
* Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within 45 days prior to registration)
* Calculated (Calc.) creatinine clearance \>= 30 mL/min (within 45 days prior to registration)
* Creatinine clearance (CrCl) \>= 30 mL/min estimated by Cockcroft-Gault Equation
* For African American patients specifically whose renal function is not considered adequate by the formula above, an alternative formula that takes race into account (Chronic Kidney Disease Epidemiology Collaboration CKD-EPI formula) should be used for calculating the related estimated glomerular filtration rate (GFR) with a correction factor for African American race creatinine clearance for trial eligibility, where GFR \>= 30 mL/min/1.73m\^2 will be considered adequate
* Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) (within 45 days prior to registration)
* Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =\< 3 x upper limit of normal (ULN) or \< 5 x ULN if hepatic metastases present (within 45 days prior to registration)
* Patients with known human immunodeficiency virus (HIV) on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Testing is not required for entry into protocol
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. Patients with HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load
* The patient must agree to use a highly effective contraception, including men with vasectomies if they are having sex with a woman of childbearing potential or with a woman who is pregnant, while on study drug and for 6 months following the last dose of study drug. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
* Patients with planned treatment of all metastatic disease with definitive therapy including either surgery, ablative (non-palliative) doses of radiation, or intervention of some type (definitive interventional radiology techniques) to ALL metastatic sites rendering the patient without extra-renal measurable disease. Patients NOT planned for definitive treatment of all metastatic sites are eligible. Lesions radiated palliatively are not eligible for response assessment
* Patients with untreated or unstable brain metastases or cranial epidural disease
* Note: Patients who have been adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator are eligible. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to registration as documented by MRI or CT imaging or deemed stable by clinical investigator
* Prior radiotherapy to the kidney that would result in overlap of radiation therapy fields treatment of the primary tumor
* Any systemic therapy for metastatic renal cell carcinoma (RCC) that was initiated \> 90 days before registration, note that prior chemotherapy for a different cancer is allowed (completed \> 3 years prior to registration)
* Severe, active comorbidity defined as follows:
* Active autoimmune disease requiring ongoing therapy including systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications daily. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
* History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies
* Active tuberculosis (purified protein derivative \[PPD\] response without active tuberculosis \[TB\] is allowed)
* Uncontrolled hypertension (systolic blood pressure \[BP\] \>= 190 mmHg or diastolic BP \> 110 mmHg)
* Major surgery requiring hospital admission =\< 28 days prior to registration
* Any serious (requiring hospital stay or long term rehab) non-healing wound, ulcer, or bone fracture within 45 days prior to registration
* Any arterial thrombotic (ST elevation myocardial infarction \[STEMI\], non-ST elevation myocardial infarction \[NSTEMI\], cerebrovascular accident \[CVA\], etc) events within 180 days prior to registration
* Active New York (NY) Heart Association class 3-4 heart failure symptoms
* Moderate or severe hepatic impairment (Child-Pugh B or C)
* Any history of untreated pulmonary embolism or deep venous thrombosis (DVT) within 180 days prior to registration. (Any asymptomatic or treated pulmonary embolism or asymptomatic treated deep venous thrombosis \> 30 days prior to registration is allowed)
* Unstable cardiac arrhythmia within 180 days prior to registration
* History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, bowel obstruction, or gastric outlet obstruction within 180 days prior to registration
* History of or active inflammatory bowel disease
* Malabsorption syndrome within 45 days prior to registration
* Pregnancy and individuals unwilling to discontinue nursing. For women of child bearing potential must have a negative pregnancy test =\< 45 days prior to registration BIOLOGICAL: Avelumab, DRUG: Axitinib, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, DRUG: Cabozantinib, PROCEDURE: Computed Tomography, BIOLOGICAL: Ipilimumab, DRUG: Lenvatinib, PROCEDURE: Magnetic Resonance Imaging, BIOLOGICAL: Nivolumab, BIOLOGICAL: Pembrolizumab, RADIATION: Stereotactic Ablative Radiotherapy
Metastatic Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8, Unresectable Renal Cell Carcinoma, Kidney
UT Southwestern; Parkland Health & Hospital System
Phase 2/3 Adaptive Study of VX-147 in Adult and Pediatric Participants With APOL1- Mediated Proteinuric Kidney Disease (AMPLITUDE)
The purpose of this study is to evaluate the efficacy, safety, tolerability, and pharmacokinetics (PK) of VX-147 in adult and pediatric participants with apolipoprotein L1 (APOL1)-mediated proteinuric kidney disease.
Call 214-648-5005
studyfinder@utsouthwestern.edu, ZHENGNAN.WANG@UTSouthwestern.edu
Robert Toto
ALL
10 Years to 65 Years old
PHASE2
NCT05312879
STU-2023-1084
Key
Inclusion Criteria:
* APOL1 genotype of G1/G1, G2/G2, or G1/G2
* Proteinuric kidney disease
Key Exclusion Criteria:
* Solid organ or bone marrow transplant
* Uncontrolled hypertension
* History of diabetes mellitus
* Known underlying cause of kidney disease including but not limited to sickle cell disease
Other protocol defined Inclusion/Exclusion criteria apply. DRUG: VX-147, DRUG: Placebo
Proteinuric Kidney Disease
UT Southwestern; Parkland Health & Hospital System
Neoadjuvant Lenvatinib and Pembrolizumab for IVC Tumor Thrombus
This study will be evaluating safety and efficacy of the combination of lenvatinib and pembolizumab neoaadjuvant therapy prior to surgical resection of locally advanced renal cell carcinoma with IVC tumor thrombus.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Vitaly Margulis
ALL
18 Years and over
PHASE2
NCT05319015
STU-2021-1240
Inclusion Criteria:
• Male/female participants who are at least 18 years of age on the day of signing informed consent
• Have histologically confirmed cT3-4,N0-1,M0-1 (clinical stage III-IV) diagnosis of renal cell carcinoma (any subtype) with level II-IV inferior vena cava tumor thrombus as per the Mayo classification of macroscopic venous invasion in renal cell carcinoma:
• Level 1 tumor thrombus is either at the entry of renal vein or within the IVC \< 2 cm from the confluence of renal vein and IVC
• Level II tumor thrombus extends within the IVC \> 2 cm above the confluence of renal vein and IVC, but still remains below the hepatic veins.
• Level III tumor Thrombus involves the intrahepatic IVC.
• Level IV tumor thrombus extends above diaphragm or into the right atrium.
• The primary tumor and thrombus may be assessed to be resectable or unresectable at the time of enrollment.
• Male participants: A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the 120 day neoadjuvant treatment period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period. Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 14 days prior to the first dose of study intervention.
• Criteria for known Hepatitis B and C positive subjects Hepatitis B and C screening tests are not required unless: * Known history of HBV or HCV infection * As mandated by local health authority Hepatitis B positive subjects: Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis C positive subjects: Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
• Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization
• HIV-positive participants may be enrolled.
• HIV-infected participants must have well-controlled HIV on ART, defined as:
• Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening 2. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening 3. It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months.
• Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study 5. The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers)
• Have adequate organ function as defined in the following table (Table 4). Specimens must be collected within 14 days prior to the start of study intervention.
Exclusion Criteria:
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents prior to allocation.
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. COVID-19 vaccines are permitted provided they are not live attenuated vaccines.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention with the exception of participating in the exploratory imaging trial utilizing 89Zr-DFO-Atezolizumab ImmunoPET/CT (STU-2019-0714).
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past year. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer, bladder in situ) that have undergone potentially curative therapy are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has more than three different sites of metastatic renal cell carcinoma.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and lenvatinib and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
• Has had an allogenic tissue/solid organ transplant.
• Has prolongation of QTcF interval to \>480 ms.
• Has a left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).
• Patients with an ejection fraction (LVEF) of 50 or greater are eligible to enroll on the study
• Patients with an ejection fraction (LVEF) of 40 to 49 are eligible to enroll on the study if they they DO NOT have signs of New York Heart Association Class III or IV congestive heart failure: i. NYHA Class III signs of congestive heart failure include marked limitation of physical activity - ordinary activity or movements cause significant fatigue, heart palpitations, or shortness of breath ii. NYHA Class IV signs of congestive heart failure include being unable to carry out physical activity without discomfort, having symptoms of heart failure at rest, if physical activity or movement is undertaken, discomfort increase c. Patients with an ejection fraction (LVEF) of 39 or less are not eligible to enroll on the study.
• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted.
• If urinalysis reveals proteinuria of 2+ or 500mg/dL greater based on the scale below, the patient will need to undergo a 24 hour urine collection, if the patient has 2000mg/24 hour or great of protein in the 24 hour the urine collection they are NOT ELIGIBLE for the study. If urinalysis protein is negative, trace, 1+, or urinalysis protein is reported in the range 0-499mg/dL protein, the patient IS ELIGIBLE to enroll on the study and does not need to complete a 24 hour urine collection:
• 1+ = 200 - 500 mg/24 hours
• 2+ = 500 - 1500 mg/24 hours
• 3+ = over 2500 mg/24 hours
• 4+ = over 3000 mg/24 hours.
• Uncontrolled blood pressure defined as consistently elevated blood pressure with a Systolic BP\>140 mmHg or diastolic BP \>90 mmHg in spite of an optimized regimen of antihypertensive medication are not able to enroll on the study. However, patients with borderline, isolated, or occasional elevation of blood pressure readings are eligible to enroll on the trial. If the treating physician believes the blood pressure elevation is transient the patient may enroll and blood pressure will be monitored during the study. Patients with persistent hypertension may be initiated on antihypertensive medication by the treating physician if deemed necessary and may enroll on the study. The treating physician may also adjust antihypertensive medication in the attempt to achieve a normal blood pressure while the patient is in screening and on study. It is at the discretion of the enrolling physician to continue adjusting the hypertension medication while the patient is enrolled and treated on the study to maintain adequate blood pressure readings.
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
• Patients with active Hepatitis B infection (defined as HBsAg positive and/or detectable HBV DNA).
• Patients with active Hepatitis C infection (defined as anti-HCV Ab positive and detectable HCV RNA).
• Hepatitis B and C screening tests are not required unless there is a known history of HBV and HCV infection or as mandated by local health authority.
DRUG: Neoadjuvant Lenvatinib, DRUG: Neoadjuvant Pembrolizumab, PROCEDURE: Radical nephrectomy, IVC thrombectomy, retroperitoneal lymph node dissection, DRUG: Adjuvant Pembrolizumab
Renal Cell Carcinoma, Kidney, Cardiovascular
Renal Cell Carcinoma, IVC tumor thrombus, Neoadjuvant therapy, Immunotherapy, Nephrectomy
UT Southwestern
Tiragolumab and Atezolizumab for the Treatment of Relapsed or Refractory SMARCB1 or SMARCA4 Deficient Tumors
This phase I/II trial studies how well tiragolumab and atezolizumab works when given to children and adults with SMARCB1 or SMARCA4 deficient tumors that have either come back (relapsed) or do not respond to therapy (refractory). SMARCB1 or SMARCA4 deficiency means that tumor cells are missing the SMARCB1 and SMARCA4 genes, seen with some aggressive cancers that are typically hard to treat. Immunotherapy with monoclonal antibodies, such as tiragolumab and atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Laura Klesse
ALL
12 Months and over
PHASE1
NCT05286801
STU-2022-0879
Inclusion Criteria:
* Patients must be \>= 12 months of age at the time of study enrollment. For part A, patients must be \< 18 years old at enrollment. For part B, there is no upper age limit
* The Part B (phase 2) cohorts will initially open concurrently with the part A but will only enroll patients at least 18 years of age. Patients \< 18 years of age will be included in the part B cohorts only after the tiragolumab monotherapy dose has been assessed to be safe in the part A portion
* Patients must have SMARCB1 (INI1) or SMARCA4 deficient tumors verified through institutional immunohistochemistry (IHC) or molecular confirmation of a pathologic SMARCB1 (INI1) or SMARCA4 loss or mutation in the tumor from a Clinical Laboratory Improvement Act (CLIA) certified lab with the following disease histologies:
* Renal medullary carcinoma
* Malignant rhabdoid tumor (extra-CNS)
* Atypical teratoid rhabdoid tumor (CNS)
* Poorly differentiated chordoma
* Epithelioid sarcoma
* Other SMARCB1 or SMARCA4 deficient tumors
* Note: Molecular studies will only be used if IHC is equivocal or cannot be performed. Documentation of the institutional IHC or molecular testing must be uploaded via the RAVE system
* Part A: Patients must have either measurable or evaluable disease Part B: Patients must have measurable disease per RECIST v1.1 for non-CNS tumors or CNS response criteria for CNS tumors
* Note: See protocol for specific exclusion for patients with CNS primary or metastatic disease
* Patients must have relapsed, refractory disease or newly diagnosed disease for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (Karnofsky/Lansky score of \>= 50). Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: See Developmental Therapeutics (DVL) homepage on the Children's Oncology Group (COG) Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea). Please refer to the table of myelosuppressive/Anticancer Agents on the COG website: https://www.cogmembers.org/uploadedFiles/Site/Disc/DVL/Documents/TableOfMyelosuppressiveAnti-CancerAgents.pdf
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent. See the DVL homepage on the COG Members site for commercial and investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell infusions (with or without total-body irradiation \[TBI\]):
* Autologous stem cell infusion including boost infusion: \>= 30 days
* Cellular therapy: \>= 30 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.)
* External radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 90 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, iodine I 131 metaiodobenzylguanidine \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have had prior TIGIT targeting therapy
* Patients must not have received prior therapy with an anti- PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (i.e. OX-40, CD137)
* Patients must not have received live/attenuated vaccine within 30 days of first dose of treatment
* Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
* The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are acceptable
* Treatment with systemic immunosuppressive medication (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha \[TNF-alpha\] agents) must have concluded \>= 14 days prior to study enrollment
* For patients with solid tumors without known bone marrow involvement
* Peripheral absolute neutrophil count (ANC) \>= 1000/uL (must be performed within 7 days prior to enrollment)
* For patients with solid tumors without known bone marrow involvement
* Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (must be performed within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
* A creatinine based on age/sex as follows (must be performed within 7 days prior to enrollment):
* Age; Maximum Serum Creatinine (mg/dL)
* 1 to \< 2 years; Male: 0.6; Female: 0.6
* 2 to \< 6 years; Male: 0.8; Female: 0.8
* 6 to \< 10 years; Male: 1; Female: 1
* 10 to \< 13 years; Male: 1.2; Female: 1.2
* 13 to \< 16 years; Male: 1.5; Female: 1.4
* \>= 16 years; Male: 1.7; Female: 1.4 OR- a 24 hour urine creatinine clearance \>= 70 mL/min/1.73 m\^2 (must be performed within 7 days prior to enrollment) OR- a glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard) (must be performed within 7 days prior to enrollment)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
* Patients with known Gilbert disease: Total bilirubin =\< 3 x ULN
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (must be performed within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L
* Albumin \>= 2 g/dL (must be performed within 7 days prior to enrollment)
* Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled as evidenced by no increase in seizure frequency in the prior 7 days
* Nervous system disorders (Common Terminology Criteria for Adverse Events \[CTCAE\] v5) resulting from prior therapy must be =\< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
* International normalized ratio (INR) =\< 1.5 (must be performed within 7 days prior to enrollment)
* Serum amylase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Serum lipase =\< 1.5 x ULN (must be performed within 7 days prior to enrollment)
* Grade 1 or lower calcium level
* Note: can have history of hypercalcemia as long as controlled and asymptomatic
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in female patients of childbearing potential. Female patients of childbearing potential are defined as those who are past the onset of menarche and are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, complete hysterectomy) or post-menopausal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of therapy and at least 90 days after final dose of tiragolumab and 150 days after final dose of atezolizumab, whichever is later. Abstinence is an acceptable method of birth control.
* It is not known if atezolizumab or tiragolumab are present in breast milk; however, IgG immunoglobulins are found in milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during therapy and for at least 150 days after the last dose of atezolizumab and 90 days after the last dose of tiragolumab, whichever is later
* Concomitant medications:
* Corticosteroids:
* Patients must not be receiving concomitant systemic steroid medications and \>= 14 days must have elapsed since last dose of systemic corticosteroid with the following exceptions:
* The use of physiologic doses of corticosteroids (5 mg/m\^2/day up to 10 mg/day of prednisone equivalent) is acceptable
* The use of topical, inhaled, or ophthalmic corticosteroids are acceptable
* The use of acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g. 48 hours of corticosteroids for a contrast allergy) are acceptable
* Investigational drugs: Patients who are currently receiving another investigational drug are not eligible
* Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible
* Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) during study treatment because these agents could potentially alter the efficacy and safety of study treatments would not be eligible
* Patients must not have a known hypersensitivity to any component of tiragolumab or atezolizumab injection
* History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation
* Patients who have undergone allogeneic bone marrow or allogeneic cell transplant are not eligible
* Patients with CNS metastases from non-CNS primary tumors are not eligible unless CNS metastases have been previously treated and sequential imaging shows no evidence for active disease in the CNS.
* Patients with primary CNS tumors (including ATRT) with involvement of the brainstem are not eligible. Note: Patients with ATRT with M0-M4 disease without involvement of the brain stem are allowed to participate
* Patients must not have active autoimmune disease that has required systemic treatment in the past 12 months, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy are not excluded. Replacement therapy (e.g. thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and these patients are eligible
* Patients who have active immune deficiency are not eligible
* Patients who have known active tuberculosis are not eligible
* Hepatitis B or C infection:
* Patients \< 18 years old at enrollment, who have known hepatitis B or C
* Patients \>= 18 years old at enrollment with:
* Positive hepatitis B surface antigen (HBsAg), OR
* Positive total hepatitis B core antibody (HBcAb) who have a quantitative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) \>= 500 IU/mL, OR
* Positive hepatitis C virus (HCV) antibody with a positive HCV ribonucleic acid (RNA) test
* Note: For adults (\>= 18 years old at enrollment), hepatitis B serology testing is required to determine eligibility. The HBV DNA test is required only for patients who have a negative HBsAg test, a negative HBsAb test, and a positive total HBcAb test. For adults (\>= 18 years old at enrollment), hepatitis C serology testing is required to determine eligibility. The HCV RNA test is required only for patients who have a positive HCV antibody test
* Patients who have a known, recent Epstein-Barr virus (EBV) infection or known history of chronic, active infection are not eligible
* Patients who have history of or active human immunodeficiency virus (HIV) are not eligible except patients who are stable on anti-retroviral therapy, have a CD4 count \>= 200/uL, and have an undetectable viral load
* Patients who have significant cardiovascular disease (such as New York Heart Association class III or IV congestive heart failure, myocardial infarction, or cerebrovascular accident) within 3 months prior to study enrollment, unstable arrhythmia, or unstable angina are not eligible
* Patients who have a major surgical procedure, other than for diagnosis, within 4 weeks prior to study enrollment, or the anticipation of the need for a major surgical procedure during the study are not eligible
* Patients who have a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or known active pneumonitis are not eligible. History of radiation pneumonitis in the radiation field is permitted
* Patients who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) are not eligible. Patients with indwelling catheters (e.g., PleurX) are allowed
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible BIOLOGICAL: Atezolizumab, PROCEDURE: Biospecimen Collection, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, OTHER: Fludeoxyglucose F-18, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Positron Emission Tomography, BIOLOGICAL: Tiragolumab, PROCEDURE: X-Ray Imaging
Atypical Teratoid/Rhabdoid Tumor, Epithelioid Sarcoma, Kidney Medullary Carcinoma, Malignant Solid Neoplasm, Poorly Differentiated Chordoma, Recurrent Atypical Teratoid/Rhabdoid Tumor, Recurrent Chordoma, Recurrent Epithelioid Sarcoma, Recurrent Kidney Medullary Carcinoma, Recurrent Malignant Solid Neoplasm, Recurrent Rhabdoid Tumor, Refractory Atypical Teratoid/Rhabdoid Tumor, Refractory Chordoma, Refractory Epithelioid Sarcoma, Refractory Kidney Medullary Carcinoma, Refractory Malignant Solid Neoplasm, Refractory Rhabdoid Tumor, Rhabdoid Tumor, Bones and Joints, Soft Tissue
Children’s Health
Evaluating the Addition of the Immunotherapy Drug Atezolizumab to Standard Chemotherapy Treatment for Advanced or Metastatic Neuroendocrine Carcinomas That Originate Outside the Lung
This phase II/III trial compares the effect of immunotherapy with atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone for the treatment of poorly differentiated extrapulmonary (originated outside the lung) neuroendocrine cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). The other aim of this trial is to compare using atezolizumab just at the beginning of treatment versus continuing it beyond the initial treatment. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. Giving atezolizumab in combination with a platinum drug (cisplatin or carboplatin) and etoposide may work better in treating patients with poorly differentiated extrapulmonary neuroendocrine cancer compared to standard therapy with a platinum drug (cisplatin or carboplatin) and etoposide alone.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
Namrata Peswani
ALL
18 Years and over
PHASE2
NCT05058651
STU-2023-0750
Inclusion Criteria:
* Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC)
* Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator
* Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and nonmeasurable lesions must be assessed by CT scan with IV contrast of the chest/abdomen/and pelvis (or CT chest without contrast and MRI abdomen/pelvis with gadolinium contrast, if contraindication to CT iodinated contrast) within 28 days prior to registration. While may be used for routine clinical evaluation, PET scans and bone scans alone are not acceptable for disease assessment while participating in this study. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form
* Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) if clinically indicated within 28 days prior to registration. Note: Brain imaging is not required in participants without known and/or clinical concern for brain metastases. Participants with asymptomatic central nervous system (CNS) metastases are eligible if one or more of the following apply:
* Participants who have received treatment for brain metastases must have:
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* Discontinued all corticosteroids at least 14 days prior to registration
* Participants with treatment-naive brain lesions must have:
* No lesion measuring \> 2.0 cm in size in any axis
* MRI brain or CT head with contrast (if there is contraindication to MRI brain) demonstrating no evidence for mass effect, edema, or other impending neurological compromise within 28 days prior to registration
* No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration
* No need for \> 2 mg of dexamethasone (or equivalent of \> 10 mg prednisone) per day at time of registration
* Participants must not have symptomatic central nervous system (CNS) metastases
* Participants must not have known or suspected leptomeningeal disease
* Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinum-based therapy +/- radiation +/- surgery provided that all therapy was completed \>= 6 months prior to registration
* Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study
* Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed \>= 24 weeks prior to registration and participants have recovered from all prior toxicities to =\< grade 1.
* Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, antiPD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least 12 months prior to study registration
* Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 \[IL-2\] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to registration
* Participants must not have had history of known severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, including to Chinese hamster ovary cell products or to any component of the atezolizumab formulation, cisplatin, carboplatin, or etoposide
* Participants must not be on active systemic therapy for another cancer with the exception of hormonal therapy including androgen deprivation therapy (e.g., gonadotropin-releasing hormone \[GnRH\] agonists or antagonists), which can be continued while participants are receiving protocol therapy. Use of enzalutamide or apalutamide is permitted after completion of chemotherapy and must be held during chemotherapy for participants receiving prior to enrollment. Use of darolutamide is permitted during chemotherapy. Glucocorticoid-containing regimens, including abiraterone, are not permitted.
* Participants must be \>= 18 years of age
* Participants must have a Zubrod performance status of =\< 2 within 28 days prior to registration
* Participants must have a complete medical history and physical exam within 28 days prior to registration
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9 /L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Hemoglobin \>= 9.0 g/dl (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Platelet count \>= 100 x 10\^9/L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Serum total bilirubin =\< 1.5 x ULN (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Adequate renal function as defined by any 1 of the following: 1) Measured creatinine clearance (CL) \> 50 mL/min OR 2) Calculated creatinine CL \> 50 mL/min by the Cockcroft-Gault formula OR by 24-hour urine collection for determination of creatinine clearance (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests)
* Participants must not have uncontrolled or symptomatic hypercalcemia (\> 1.5 mmol/L ionized calcium or calcium \> 12 mg/dL or corrected serum calcium \> ULN) within 14 days prior to registration. Participants who have asymptomatic hypercalcemia are eligible provided that medical therapy to treat the hypercalcemia is planned
* Participants must not have a diagnosis of immunodeficiency nor be receiving systemic steroid therapy (equivalent of \> 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 14 days prior to registration
* Participants must not have active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:
* Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
* Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
* Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
* Rash must cover \< 10% of body surface area
* Disease is well controlled at baseline and requires only low-potency topical corticosteroids
* No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
* Participants must not have history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
* Participants must not have significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction within 3 months prior to registration, unstable arrythmias, or unstable angina
* Participants must not have had a major surgical procedure other than for diagnosis within 28 days prior to registration. Participant must not plan to receive a major surgical procedure during the course of protocol treatment. NOTE: Patient port placement is not considered a major surgery
* Participants must not have severe infections (i.e., Common Terminology Criteria for Adverse Events \[CTCAE\] grade \>= 2) at time of registration, including but not limited to hospitalization for complications for infection, bacteremia, or severe pneumonia
* Participants must not have known active tuberculosis
* Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load, with testing performed as clinically indicated
* Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load, with testing performed as clinically indicated
* Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months of registration
* Participants must not have prior allogeneic bone marrow transplantation or solid organ transplant
* Participants must not have received administration of a live, attenuated vaccine (e.g., FluMist \[registered trademark\]) within 28 days prior to initiation of study treatment, during treatment with atezolizumab, and not plan to receive for 5 months after the last dose of atezolizumab
* Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method (with details provided as a part of the consent process) during the treatment period and for 5 months after the final dose of atezolizumab. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a sideeffect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines BIOLOGICAL: Atezolizumab, PROCEDURE: Biospecimen Collection, DRUG: Carboplatin, DRUG: Cisplatin, PROCEDURE: Computed Tomography, DRUG: Etoposide, PROCEDURE: Magnetic Resonance Imaging, OTHER: Patient Observation
Advanced Extrapulmonary Neuroendocrine Carcinoma, Metastatic Extrapulmonary Neuroendocrine Carcinoma, Recurrent Extrapulmonary Neuroendocrine Carcinoma, Unresectable Extrapulmonary Neuroendocrine Carcinoma, Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Cervix, Colon, Corpus Uteri, Esophagus, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Hematopoietic, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Urinary Bladder
UT Southwestern; Parkland Health & Hospital System
[18F]PT2385 PET/CT in Patients with Renal Cell Carcinoma
This is an exploratory study to assess \[18F\]PT2385 Positron Emission Tomography/Computed Tomography (PET/CT) in patients with renal cell carcinoma (RCC). This is an open-label, nontherapeutic trial. The main objective is to correlate hypoxia-inducible factor-2alpha (HIF2α) levels as determined by an investigational \[18F\]PT2385 PET/CT scan with the levels on subsequently obtained tissue by HIF2α immunohistochemistry (IHC). There will be three cohorts. The first pre-surgical cohort will have \[18F\]PT2385 PET/CT prior to nephrectomy. The uptake and retention on Positron Emission Tomography (PET), quantified as standardized uptake value (SUV) max and mean, abbreviated SUV henceforth will be correlated with HIF2α levels by IHC on the primary tumor. The second cohort will comprise patients with metastatic clear cell renal carcinoma (ccRCC). SUV will be correlated with HIF2α levels measured by IHC on a biopsy sample from a metastasis. Both low- and high-avidity sites will be biopsied and tracer uptake correlated with HIF2α IHC. A third cohort will include patients with Von Hippel-Lindau (VHL) syndrome and any of the following disease manifestations - RCC, central nervous system (CNS) hemangioblastoma, and/or pancreatic neuroendocrine tumor(s). Investigational imaging will evaluate HIF2α expression within a tumor type and across different tumor types. A biopsy is encouraged but not mandatory for this cohort.
Call 833-722-6237
canceranswerline@utsouthwestern.edu
James Brugarolas
ALL
18 Years and over
PHASE1
NCT04989959
STU-2021-0592
Inclusion Criteria:
* Ability to understand and the willingness to sign a written informed consent that includes study interventions (PET/CT and, if cohort 2, mandatory biopsy).
* Ability to lie still for a 30- to 60-minute PET/CT scan.
* One of the following:
• Cohort 1. Patients with suspected RCC planned for surgery.
• Cohort 2. Patients with metastatic ccRCC or VHL syndrome and RCC. Biopsy is required (planned resection for treatment reasons of a metastatic site is acceptable in lieu of the biopsy).
• Cohort 3. Patients with VHL syndrome with RCC, CNS hemangioblastoma, and/or pancreatic neuroendocrine tumor(s) planning to start belzutifan. * Patients with liver dysfunction will be considered "patients of special interest," and enrollment is allowed with or without criteria outlined for Cohorts 1-3. Liver dysfunction is defined clinically and is typically supported by abnormalities in imaging or laboratory studies (alanine / aspartate amino-transferase, bilirubin, alkaline phosphatase, or international normalized range (INR) for prothrombin time). * Women of child-bearing potential must agree to undergo and have documented a negative pregnancy test on the day of \[18F\]PT2385 administration. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Exclusion Criteria:
* Uncontrolled severe and irreversible intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
* Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
* Claustrophobia or other contraindications to PET/CT.
* Subjects must not weigh more than the maximum weight limit for the table for the PET/CT scanner where the study is being performed (\>200 kilograms or 440 pounds).
* For cohort 2 patients, lack of suitable sites for mandatory biopsy. For example, patients with metastatic disease restricted to the lungs that would require percutaneous biopsies with associated risk of bleeding and pneumothorax will be excluded. DRUG: [18F]PT2385, PROCEDURE: Positron Emission Tomography/Computed Tomography, PROCEDURE: Biopsy
Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma, Kidney
UT Southwestern; Parkland Health & Hospital System