- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05361720
Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study
Optimal Treatment by Invoking Biologic Clusters in Renal Cell Carcinoma (OPTIC RCC)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:
I. To improve objective response rate of front-line therapy in advanced renal cell carcinoma (RCC) by prospectively assigning ipilimumab/nivolumab or nivolumab/cabozantinib according to a patient's ribonucleic acid sequence (RNAseq)-defined biologic cluster.
SECONDARY OBJECTIVE:
I. To assess clinical outcome of cluster-assigned treatment in front-line metastatic renal cell carcinoma (mRCC).
EXPLORATORY OBJECTIVE:
I. To assess tissue and peripheral blood for pharmacodynamic correlations with response to treatment.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I:
INDUCTION: Patients receive ipilimumab and nivolumab intravenously (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.
ARM II: Patients receive nivolumab IV on day 1 and cabozantinib orally (PO) once a day (QD). Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days from last dose.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Vanderbilt-Ingram Service for Timely Access
- Phone Number: 800-811-8480
- Email: cip@vumc.org
Study Locations
-
-
California
-
Duarte, California, United States, 91010
- Recruiting
- City of Hope National Medical Center
-
Contact:
- Vanderbilt-Ingram Services for Timely Access
- Email: cip@vumc.org
-
Principal Investigator:
- Sumantra Pal, MD
-
Orange, California, United States, 92868
- Recruiting
- Chao Family Comprehensive Cancer Center
-
Principal Investigator:
- Nataliya Mar, MD
-
Contact:
- Vanderbilt-Ingram Services for Timely Access
- Email: cip@vumc.org
-
-
Ohio
-
Cleveland, Ohio, United States, 44195
- Recruiting
- Cleveland Clinic
-
Principal Investigator:
- Moshe Ornstein, MD
-
Contact:
- Vanderbilt-Ingram Services for Timely Access
- Email: cip@vumc.org
-
Cleveland, Ohio, United States, 44106
- Recruiting
- University Hospitals Seidman Cancer Center
-
Principal Investigator:
- Pedro Barata, MD
-
Contact:
- Vanderbilt-Ingram Services for Timely Access
- Email: cip@vumc.org
-
-
Tennessee
-
Nashville, Tennessee, United States, 37232
- Recruiting
- Vanderbilt University/Ingram Cancer Center
-
Principal Investigator:
- Brian I. Rini, MD
-
Contact:
- Vanderbilt-Ingram Service for Timely Access
- Phone Number: 800-811-8480
- Email: cip@vumc.org
-
-
Texas
-
Dallas, Texas, United States, 75390
- Recruiting
- University of Texas, Southwestern Medical Center
-
Contact:
- Vanderbilt-Ingram Services for Timely Access
- Phone Number: 800-811-8480
- Email: cip@vumc.org
-
Principal Investigator:
- Tian Zhang, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I (ipilimumab, nivolumab)
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. |
Given IV
Other Names:
Given IV
Other Names:
|
Experimental: Arm II (nivolumab, cabozantinib)
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.
|
Given IV
Other Names:
Given PO
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate (ORR) (Arm 1)
Time Frame: Up to 4 years
|
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)
Time Frame: Up to 4 years
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression free survival
Time Frame: Up to 4 years
|
Possible risk factors will be compared for survival with Kaplan-Meier estimates and log-rank tests.
The proportional hazards model will be used for adjusting tests of significance and estimating the hazard ratios.
Will apply the generalized estimating equation (GEE) statistical procedure for longitudinal binary data analysis with multiple observable vectors for the same subject.
For the continuous multiple time points or correlated data, will use the mixed effects model to conduct the profile analysis.
The adjusted 95% CIs will be reported.
|
Up to 4 years
|
Depth of response > 80%
Time Frame: At 6 months
|
Will apply the GEE statistical procedure for longitudinal binary data analysis with multiple observable vectors for the same subject.
For the continuous multiple time points or correlated data, will use the mixed effects model to conduct the profile analysis.
The adjusted 95% CIs will be reported.
|
At 6 months
|
Incidence of immune-related adverse events
Time Frame: Up to 4 years
|
Adverse medical events will be tabulated.
National Cancer Institute toxicity grade 3 and grade 4 laboratory abnormalities will be listed.
|
Up to 4 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Brian I Rini, MD, Vanderbilt University/Ingram Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Kidney Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Carcinoma, Renal Cell
- Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
- Ipilimumab
Other Study ID Numbers
- VICCURO21103 (Other Identifier: Vanderbilt University/Ingram Cancer Center)
- P30CA068485 (U.S. NIH Grant/Contract)
- NCI-2022-03150 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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