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

NCT ID: NCT06049576

Last Updated: 2025-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE1

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-06

Study Completion Date

2026-03-14

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVE:

I. To determine the effect of camu camu in combination with nivolumab/ipilimumab on Ruminococcus abundance in stool samples of patients with metastatic renal cell carcinoma (mRCC).

SECONDARY OBJECTIVES:

I. To evaluate the effect of camu camu on the clinical efficacy of the nivolumab/ipilimumab combination.

II. To determine the effect of camu camu on systemic immunodulation of the nivolumab/ipilimumab combination in patients with mRCC.

III. To describe the toxicity and safety profile of the use of camu camu in combination with nivolumab/ipilimumab.

IV. To determine the effect of camu camu on gut microbiome diversity and function.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients receive nivolumab intravenously (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 computed tomography (CT) and/or bone scan and/or magnetic resonance imaging (MRI) on trial.

ARM 2: Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu orally (PO) once a day (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.

After completion of study treatment, patients are followed up every 12 weeks until time of death or formal withdrawal from the study, whichever comes first.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1 (nivolumab and ipilimumab)

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.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood and stool sample collection

Bone Scan

Intervention Type PROCEDURE

Undergo bone scan

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Ipilimumab

Intervention Type BIOLOGICAL

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Arm 2 (nivolumab, ipilimumab, camu camu)

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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood and stool sample collection

Bone Scan

Intervention Type PROCEDURE

Undergo bone scan

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Ipilimumab

Intervention Type BIOLOGICAL

Given IV

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Myrciaria dubia Prebiotic Supplement

Intervention Type DRUG

Given PO

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Biospecimen Collection

Undergo blood and stool sample collection

Intervention Type PROCEDURE

Bone Scan

Undergo bone scan

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Ipilimumab

Given IV

Intervention Type BIOLOGICAL

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Myrciaria dubia Prebiotic Supplement

Given PO

Intervention Type DRUG

Nivolumab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Bone Scintigraphy CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography CT CT Scan tomography Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody BMS-734016 Ipilimumab Biosimilar CS1002 MDX-010 MDX-CTLA4 Yervoy 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 Camu Camu Prebiotic Camu-camu Prebiotic Myrciaria dubia based Prebiotic Myrciaria dubia Supplement BMS-936558 CMAB819 MDX-1106 NIVO Nivolumab Biosimilar CMAB819 ONO-4538 Opdivo

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Platelets \< 100,000/mm\^3
* AST or ALT \> 3 x ULN (\> 5 x ULN if liver metastases are present)
* Total bilirubin \> 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin 3.0 mg/dL)
* Calculated creatinine clearance \<30 millimeters per minute (mL/min) per the Cockcroft and Gault formula or serum creatinine \> 1.5 x upper limit of normal (ULN)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

City of Hope Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sumanta K Pal

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

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City of Hope Medical Center

Duarte, California, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2023-06703

Identifier Type: REGISTRY

Identifier Source: secondary_id

22457

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

22457

Identifier Type: -

Identifier Source: org_study_id