Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial.
Nazli Dizman, Luis Meza, Paulo Bergerot...
https://pubmed.ncbi.nlm.nih.gov/35228755Actively Recruiting
Phase 1
Age: 18Years +
All Genders
ID06399419
CBM588 Capsules Combined With Nivolumab and Ipilimumab for Advanced Stage Kidney Cancer An Open-Label, Phase I Dose-Finding Study for Metastatic Renal Cell Carcinoma
Led by Osel, Inc. · Updated on 2024-05-30
28
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
O
Osel, Inc.
Lead Sponsor
C
City of Hope Medical Center
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety, side effects, best dose, and effectiveness of CBM588 capsules combined with nivolumab and ipilimumab in treating patients with advanced kidney cancer that has spread to nearby tissue, lymph nodes, or distant parts of the body. This phase I trial focuses on metastatic renal cell carcinoma, aiming to see how the combination affects the immune system and gut microbiome while monitoring tolerability and clinical benefits. Participants receive CBM588 capsules orally twice daily on days 1-21, along with nivolumab and ipilimumab given intravenously on day 1 of each 21-day cycle for four cycles. After this, they continue with CBM588 capsules twice daily on days 1-28 and nivolumab intravenously every 28 days if the disease does not progress or toxicity is unacceptable. The study includes dose escalation followed by dose expansion phases. Imaging scans like CT and bone scans are performed throughout, with optional MRI. During the study, participants provide blood samples and undergo various imaging tests to monitor disease and safety. Researchers assess dose-limiting toxicities, maximum tolerated dose, adverse events, progression-free survival, overall response rate, and changes in gut microbiome and metabolic pathways. Follow-up occurs once a year after treatment completion, with assessments continuing for up to three years to evaluate long-term safety and effects.
CONDITIONS
Brief Title
CBM588 Capsules in Combination With Nivolumab and Ipilimumab for the Treatment of Advanced Stage Kidney Cancer
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Provided documented informed consent
- Agreed to allow use of archival tumor tissue or obtained PI approval if unavailable
- ECOG performance status 0 to 2
- Aged 18 years or older
- Histologically confirmed renal cell carcinoma with clear cell or sarcomatoid component
- Advanced or metastatic renal cell carcinoma with intermediate- or poor-risk disease by IMDC criteria
- No prior systemic therapy for renal cell carcinoma except one prior adjuvant/neoadjuvant therapy if recurrence occurred after 6 months
- Measurable disease by RECIST 1.1
- Recovered from prior anticancer therapy toxic effects to grade 1 or less (except alopecia)
- Absolute neutrophil count ≥ 1500/uL without growth factor support
- White blood cell count ≥ 2500/uL
- Platelet count ≥ 100,000/uL without transfusion
- Hemoglobin ≥ 8 g/dL
- Liver enzymes ALT, AST, ALP ≤ 3 times ULN; ALP ≤ 5 times ULN with bone metastases
- Total bilirubin ≤ 1.5 times ULN (≤ 3 times ULN for Gilbert's disease)
- Serum albumin ≥ 2.8 g/dL
- Coagulation tests PT/INR or PTT < 1.3 times ULN
- Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault equation)
- Use of effective contraception during study and for specified months after last nivolumab dose
- Female participants of childbearing potential must not be pregnant at screening per defined criteria
You will not qualify if you...
- Prior treatment with ipilimumab and/or nivolumab
- Current or planned use of probiotics, yogurt, or bacterial fortified foods during treatment
- History of allergic reactions to similar study agents
- Active or history of interstitial lung disease/pneumonitis requiring steroid treatment
- Medical conditions increasing risk or interfering with safety interpretation
- Receipt of recent systemic anticancer therapy or radiation within specified time frames
- Known brain metastases unless stable and treated with complete wound healing
- Use of live attenuated vaccine within 30 days before study treatment
- Uncontrolled or recent significant illness including infections and immune conditions
- Active known or suspected autoimmune disease except certain controlled conditions
- Pregnant or lactating females
- Inability to swallow capsules or receive IV administration
- Known allergy to study treatments or severe infusion reactions
- Other active malignancy requiring treatment within 3 years except certain cured cancers
- History of serious cardiac conditions or low oxygen levels at baseline
- Any condition judged unsafe by investigator or interfering with study procedures
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Up to 3 years or until disease progression or unacceptable toxicity
Participants receive CBM588 capsules orally twice daily combined with nivolumab and ipilimumab intravenously in repeated cycles. The first part includes 4 cycles of 21 days each with CBM588 on days 1-21 and nivolumab and ipilimumab on day 1. This is followed by cycles of 28 days with CBM588 on days 1-28 and nivolumab on day 1, continuing until disease progression or unacceptable toxicity. Participants also undergo CT scans, bone scans, and blood sample collections throughout treatment. Optional MRI scans may be performed.
1 visit per cycle every 21 days for 4 cycles, then 1 visit per cycle every 28 days thereafter
Follow-up
Duration - Up to 3 years
After completing treatment, participants are followed up once a year to monitor their health status.
Annual follow-up visits
Trial Site Locations
Total: 1 location
1
City of Hope Medical Center
Duarte, California, United States, 91010
Actively Recruiting
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How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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Published Research Related To This Trial
Association of Probiotic Clostridium butyricum Therapy with Survival and Response to Immune Checkpoint Blockade in Patients with Lung Cancer.
Yusuke Tomita, Tokunori Ikeda, Shinya Sakata...
https://pubmed.ncbi.nlm.nih.gov/32665261Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors.
Yusuke Tomita, Yoshihiko Goto, Shinya Sakata...
https://pubmed.ncbi.nlm.nih.gov/35655708Association of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations.
Yusuke Tomita, Shinya Sakata, Kosuke Imamura...
https://pubmed.ncbi.nlm.nih.gov/38201474The biotherapeutic Clostridium butyricum MIYAIRI 588 strain potentiates enterotropism of Rorγt+Treg and PD-1 blockade efficacy.
Thomas Paz Del Socorro, Kentaro Oka, Olivier Boulard...
https://pubmed.ncbi.nlm.nih.gov/38385162