IRB Study Number 23-307
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objective:
• To improve objective response rate of front-line therapy in advanced RCC by prospectively assigning ipilimumab/nivolumab or nivolumab/cabozantinib according to a patient’s RNAseq-defined biologic cluster.
Secondary Objective:
• To assess clinical outcome of cluster-assigned treatment in front-line mRCC.
Exploratory Objective:
• To assess tissue and peripheral blood for pharmacodynamic correlations with response to treatment
Inclusion Criteria
Histological confirmation of RCC with a clear cell component.
Advanced (not amenable to curative surgery or radiation therapy) or metastatic (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% (Appendix 1).
No prior systemic therapy for RCC in the neoadjuvant, adjuvant or metastatic setting.
At least one measurable lesion as defined by RECIST 1.1.
Tumor tissue for RNA-sequencing (tumor tissue from bony metastasis is not suitable but a soft tissue component around bone is acceptable) (see Section 6.3).
• 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 (Appendix 2).
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×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 (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 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 (Appendix 3).
• 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 CNS metastases are eligible after they have completed local therapy (eg, whole brain radiation therapy [WBRT], surgery or radiosurgery). There is no washout period after local therapy and no additional imaging outside of required baseline imaging is required.
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.
• 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).
