Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study
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 tumors 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.
Kidney (Renal Cell)
Phase II
Adults
Mol. targeted/Immunotherapy/Biologics
Cabozantinib,
Ipilimumab,
Nivolumab,
XL184
Rini, Brian
National
City of Hope National Medical Center, Georgetown University, Seidman Cancer Center at University Hospitals, The Cleveland Clinic, UC Irvine Health/Chao Family CCC, UT Southwestern Medical Center, Vanderbilt University
10-26-2022
Eligibility
18 Years
BOTH
NO
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.
Calculated creatinine clearance >= 30 mL/min per the Cockcroft and Gault formula
Total bilirubin = 1.5 times the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilberts 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 cabozantinib/nivolumab [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., Crohns 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)
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.
Calculated creatinine clearance >= 30 mL/min per the Cockcroft and Gault formula
Total bilirubin = 1.5 times the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilberts 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 cabozantinib/nivolumab [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., Crohns 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)
