search
Back to results

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

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Biospecimen Collection
Bone Scan
Computed Tomography
Ipilimumab
Magnetic Resonance Imaging
Myrciaria dubia Prebiotic Supplement
Nivolumab
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Clear Cell Renal Cell Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • City of Hope Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm 1 (nivolumab and ipilimumab)

Arm 2 (nivolumab, ipilimumab, camu camu)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Abundance of ruminococcus in the stool
Using a two-group t-test with a one-sided type I error of 0.05.

Secondary Outcome Measures

Best overall response
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Will be examined using Fisher's exact test.
Progression-free survival (PFS)
PFS, assessed as the duration of time from enrollment to progression, with camu camu in combination with nivolumab/ipilimumab vs nivolumab/ipilimumab alone. The difference in progression-free survival across the two groups will be explored graphically using Kaplan-Meier survival plots. Median progression-free survival time for each of the two arms will be reported and Cox Proportional Hazards model will be used to estimate the hazard ratio and its confidence interval.
Incidence of adverse events
Will perform statistical analysis to compare the rates of all grade and grade >= 3 (per Common Terminology Criteria for Adverse Events version 5) treatment related adverse events between nivolumab/ipilimumab and nivolumab/ipilimumab with camu camu arms.

Full Information

First Posted
September 7, 2023
Last Updated
September 19, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT06049576
Brief Title
Nivolumab and Ipilimumab With and Without Camu Camu for the Treatment of Patients With Metastatic Renal Cell Carcinoma
Official Title
Combination Nivolumab and Ipilimumab With and Without Camu Camu in First Line Treatment of Metastatic Renal Cell Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 25, 2023 (Anticipated)
Primary Completion Date
January 8, 2025 (Anticipated)
Study Completion Date
January 8, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clear Cell Renal Cell Carcinoma, Sarcomatoid Renal Cell Carcinoma, Stage III Renal Cell Cancer AJCC v8, Stage IV Renal Cell Cancer AJCC v8

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1 (nivolumab and ipilimumab)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Arm 2 (nivolumab, ipilimumab, camu camu)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo blood and stool sample collection
Intervention Type
Procedure
Intervention Name(s)
Bone Scan
Other Intervention Name(s)
Bone Scintigraphy
Intervention Description
Undergo bone scan
Intervention Type
Procedure
Intervention Name(s)
Computed Tomography
Other Intervention Name(s)
CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography
Intervention Description
Undergo CT
Intervention Type
Biological
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Magnetic Resonance Imaging
Other Intervention Name(s)
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
Intervention Description
Undergo MRI
Intervention Type
Drug
Intervention Name(s)
Myrciaria dubia Prebiotic Supplement
Other Intervention Name(s)
Camu Camu Prebiotic, Camu-camu Prebiotic, Myrciaria dubia based Prebiotic, Myrciaria dubia Supplement
Intervention Description
Given PO
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Abundance of ruminococcus in the stool
Description
Using a two-group t-test with a one-sided type I error of 0.05.
Time Frame
From baseline to week 12 of therapy
Secondary Outcome Measure Information:
Title
Best overall response
Description
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Will be examined using Fisher's exact test.
Time Frame
Every 12 weeks for up to 3 years
Title
Progression-free survival (PFS)
Description
PFS, assessed as the duration of time from enrollment to progression, with camu camu in combination with nivolumab/ipilimumab vs nivolumab/ipilimumab alone. The difference in progression-free survival across the two groups will be explored graphically using Kaplan-Meier survival plots. Median progression-free survival time for each of the two arms will be reported and Cox Proportional Hazards model will be used to estimate the hazard ratio and its confidence interval.
Time Frame
Time from enrollment to progression date or date of death, whichever occurs first (Each cycle is 4 weeks)
Title
Incidence of adverse events
Description
Will perform statistical analysis to compare the rates of all grade and grade >= 3 (per Common Terminology Criteria for Adverse Events version 5) treatment related adverse events between nivolumab/ipilimumab and nivolumab/ipilimumab with camu camu arms.
Time Frame
Up to 30 days post-last dose of protocol therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sumanta K Pal
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sumanta K. Pal
Phone
626-359-8111
Email
SPal@coh.org
First Name & Middle Initial & Last Name & Degree
Sumanta K. Pal

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs