Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study

NCT05361720 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: VICCURO21103NCI-2022-03150P30CA068485CDMRP-KC210255
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Overall response rate (ORR) (Arm 1)

  Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. ORR = complete response (CR) + partial response (PR). The Agresti-Coull two-sided 95% confidence intervals (CIs) for the success rate will be reported.

  Up to 4 years

• Overall response rate (Arm 2)

  Assessed per RECIST 1.1. ORR = CR + PR. The Agresti-Coull two-sided 95% CIs for the success rate will be reported.

  Up to 4 years

Secondary Outcomes (3)

• Progression free survival

  Up to 4 years

• Depth of response > 80%

  At 6 months

• Incidence of immune-related adverse events

  Up to 4 years

Study Arms (2)

Arm I (ipilimumab, nivolumab)

EXPERIMENTAL

INDUCTION: Patients receive ipilimumab and nivolumab IV on day 1. Cycles repeat every 21 days for 4 cycles. MAINTENANCE: Patients receive nivolumab IV on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Biological: Nivolumab

Arm II (nivolumab, cabozantinib)

EXPERIMENTAL

Patients receive nivolumab IV on day 1 and cabozantinib PO QD. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib; Biological: Nivolumab

Interventions

Cabozantinib DRUG

Given PO

Arm II (nivolumab, cabozantinib)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Arm I (ipilimumab, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Arm I (ipilimumab, nivolumab); Arm II (nivolumab, cabozantinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• =\< 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

Sponsors & Collaborators

• Vanderbilt-Ingram Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• United States Department of Defense: collaborator

Study Sites (6)

City of Hope National Medical Center

Duarte, California, 91010, United States

RECRUITING

Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

University of Texas, Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma; Carcinoma, Renal Cell

Interventions

cabozantinib; Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Study Officials

• Brian I Rini, MD

  Vanderbilt University/Ingram Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanderbilt-Ingram Service for Timely Access

CONTACT

800-811-8480; cip@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 25, 2022
• First Posted: May 5, 2022
• Study Start: December 6, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

US (6)