Genetic testing to choose the best treatment for advanced kidney cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase II trial evaluates the effectiveness of using genetic testing of tumor tissue to determine the most suitable treatment for patients with advanced or metastatic clear cell renal cell carcinoma. Participants will be assigned to one of two treatment arms: one receiving a combination of immunotherapy drugs (nivolumab and ipilimumab) and the other receiving nivolumab along with an oral targeted therapy (cabozantinib). The study aims to improve the objective response rate by tailoring therapy based on the patient's RNA sequencing-defined biological cluster. Patients will be monitored for clinical outcomes and pharmacodynamic responses to treatment.

Why it matters

Who can join: the full rules

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)

Where it's running

• City of Hope National Medical Center
  Duarte, California, United States Recruiting
• Chao Family Comprehensive Cancer Center
  Orange, California, United States Recruiting
• University Hospitals Seidman Cancer Center
  Cleveland, Ohio, United States Recruiting
• Cleveland Clinic
  Cleveland, Ohio, United States Recruiting
• Vanderbilt University/Ingram Cancer Center
  Nashville, Tennessee, United States Recruiting
• University of Texas, Southwestern Medical Center
  Dallas, Texas, United States Recruiting

Study contacts

• Principal investigator: Brian I Rini, MD — Vanderbilt University/Ingram Cancer Center
• Study coordinator: Vanderbilt-Ingram Service for Timely Access
• Email: cip@vumc.org
• Phone: 800-811-8480

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• VSV-IFNβ-NIS plus ipilimumab and nivolumab for advanced or metastatic clear cell renal cell carcinoma

  This trial adds a virus-based therapy (VSV-IFNβ-NIS) to standard immunotherapy (ipilimumab and nivolumab) to see if it helps people with advanced or metastatic clear cell renal cell cancer.

  Recruiting Phase 2 Mayo Clinic · Rochester, Minnesota · NCT07510334

• Adding a probiotic to standard immunotherapy for advanced kidney cancer

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• Nivolumab and ipilimumab with or without EXL01 for advanced or metastatic clear-cell and sarcomatoid renal cell carcinoma

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• Using 18F-TRX to image solid tumors

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• Inulin gel plus ipilimumab and nivolumab for advanced kidney (renal cell) cancer

  This trial tests whether adding an inulin gel to the immunotherapy drugs ipilimumab and nivolumab helps people with locally advanced or metastatic clear cell or sarcomatoid renal cell carcinoma.

  Recruiting Phase 1/2 University of Michigan Rogel Cancer Center · Ann Arbor, Michigan · NCT06866262

• Predicting how tumors respond to immune therapies using a live diagnostic platform

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.