Nivolumab and Ipilimumab With and Without Camu Camu for the Treatment of Patients With Metastatic Renal Cell Carcinoma

NCT06049576 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 22457NCI-2023-06703P30CA033572
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, and best dose of camu camu when used in combination with nivolumab and ipilimumab in treating patients with kidney cancer that has spread to other places in the body. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Camu camu is a prebiotic that may have a beneficial effect on the immune system. Giving camu camu in combination with nivolumab and ipilimumab may kill more tumor cells than nivolumab and ipilimumab alone in patients with metastatic kidney cancer.

Conditions

Clear Cell Renal Cell Carcinoma; Sarcomatoid Renal Cell Carcinoma; Stage III Renal Cell Cancer AJCC v8; Stage IV Renal Cell Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Abundance of ruminococcus in the stool

  Using a two-group t-test with a one-sided type I error of 0.05.

  From baseline to week 12 of therapy

Secondary Outcomes (3)

• Best overall response

  Every 12 weeks for up to 3 years

• Progression-free survival (PFS)

  Time from enrollment to progression date or date of death, whichever occurs first (Each cycle is 4 weeks)

• Incidence of adverse events

  Up to 30 days post-last dose of protocol therapy

Study Arms (2)

Arm 1 (nivolumab and ipilimumab)

ACTIVE COMPARATOR

Patients receive nivolumab IV over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.

Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Biological: Ipilimumab; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab

Arm 2 (nivolumab, ipilimumab, camu camu)

EXPERIMENTAL

Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu PO QD continuously with each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1, and camu camu PO QD of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial.

Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Biological: Ipilimumab; Procedure: Magnetic Resonance Imaging; Drug: Myrciaria dubia Prebiotic Supplement; Biological: Nivolumab

Interventions

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Arm 1 (nivolumab and ipilimumab); Arm 2 (nivolumab, ipilimumab, camu camu)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Arm 1 (nivolumab and ipilimumab); Arm 2 (nivolumab, ipilimumab, camu camu)

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 1 (nivolumab and ipilimumab); Arm 2 (nivolumab, ipilimumab, camu camu)

Biospecimen Collection PROCEDURE

Undergo blood and stool sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm 1 (nivolumab and ipilimumab); Arm 2 (nivolumab, ipilimumab, camu camu)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Arm 1 (nivolumab and ipilimumab); Arm 2 (nivolumab, ipilimumab, camu camu)

Myrciaria dubia Prebiotic Supplement DRUG

Given PO

Also known as: Camu Camu Prebiotic, Camu-camu Prebiotic, Myrciaria dubia based Prebiotic, Myrciaria dubia Supplement

Arm 2 (nivolumab, ipilimumab, camu camu)

Nivolumab BIOLOGICAL

Given IV

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

Arm 1 (nivolumab and ipilimumab); Arm 2 (nivolumab, ipilimumab, camu camu)

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide informed consent for the trial
• Histological confirmation of renal cell carcinoma (RCC) with a clear-cell or sarcomatoid component
• Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \[AJCC\] 8 stage IV) RCC
• Intermediate or poor risk disease by International Metastatic Renal Cell Carcinoma Database Consortium Criteria (IMDC) classification
• No prior systemic therapy for RCC with the following exception:
• One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets PD-1 or PD-L1 and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Males and females, ages \>= 18
• Any ethnicity or race
• Adequate renal function defined as calculated creatinine clearance \>= 30 milliliters per minute (mL/min) per the Cockcroft and Gault formula or Serum creatinine \< 1.5 x upper limit of normal (ULN)
• Adequate liver function defined by aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x ULN (\< 5 x ULN if liver metastases are present), and total bilirubin \< 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin up to 3.0 mg/dL)
• White blood cells (WBC) \> 2,000/mm\^3
• Neutrophils \> 1,500/mm\^3
• Platelets \> 100,000/mm\^3

You may not qualify if:

• Presence of untreated brain metastases. Patients with treated brain metastases must be stable for 4 weeks after completion of treatment and have documented stability on pre-study imaging. Patients must have no clinical symptoms from brain metastases and have no requirement for systemic corticosteroids amounting to \> 10 mg/day of prednisone or its equivalent for at least 2 weeks prior to first dose of study drug. Patients with known leptomeningeal metastases are excluded, even if treated
• Favorable risk disease by IMDC classification
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
• Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
• Baseline pulse oximetry less than 92% "on room air"
• Current use, or intent to use probiotics, prebiotics, yogurt, bacterial fortified foods and other natural supplements =\< 2 week prior to treatment initiation and during the period of treatment
• Any condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Uncontrolled adrenal insufficiency
• Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
• Not recovered to =\< Grade 1 toxicities related to any prior therapy before administration of study drug
• Women who are pregnant or breastfeeding
• History of myocarditis or congestive heart failure (as defined by New York Heart Association Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry
• WBC \< 2,000/mm\^3
• Neutrophils \< 1,500/mm\^3

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Specimen Handling; Ipilimumab; CTLA-4 Antigen; Magnetic Resonance Spectroscopy; 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)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; 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; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Sumanta K Pal

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2023
• First Posted: September 22, 2023
• Study Start: October 6, 2023
• Primary Completion (Estimated): June 23, 2026
• Study Completion (Estimated): June 23, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)