Genetic testing to choose the best treatment for advanced kidney cancer
Optimal Treatment by Invoking Biologic Clusters in Renal Cell Carcinoma (OPTIC RCC)
This study is testing if using genetic testing to pick the best treatment can help people with advanced kidney cancer respond better to either a combination of immunotherapy drugs or a mix of immunotherapy and targeted therapy.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 54 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Vanderbilt-Ingram Cancer Center Academic / other |
| Drugs / interventions | radiation, prednisone, nivolumab, ipilimumab, cabozantinib, immunotherapy |
| Locations | 6 sites (Duarte, California and 5 other locations) |
| Trial ID | NCT05361720 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Ideal candidates include adults aged 18 and older with advanced or metastatic clear cell renal cell carcinoma who have not received prior systemic therapy.
Not a fit: Patients with RCC that does not have a clear cell component or those assigned to specific RNA sequencing clusters that are not eligible for treatment will not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could lead to more effective personalized treatment options for patients with advanced kidney cancer.
How similar studies have performed: Other studies have shown promise in using genetic testing to guide treatment decisions in cancer, suggesting potential success for this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
Duarte, California and 5 other locations
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.