Clinical Trials /

CBM588, Nivolumab, and Ipilimumab in Treating Patients With Stage IV or Advanced Kidney Cancer

NCT03829111

Description:

This phase I trial studies how well CBM588 works when given together with nivolumab and ipilimumab in treating patients with kidney cancer that is stage IV or has spread to other places in the body (advanced). CBM588 is a probiotic that may help to increase the effect of immunotherapy. 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. Giving CBM588, nivolumab, and ipilimumab may work better in treating patients with kidney cancer.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CBM588, Nivolumab, and Ipilimumab in Treating Patients With Stage IV or Advanced Kidney Cancer
  • Official Title: Pilot Study to Evaluate the Biologic Effect of CBM588 in Combination With Nivolumab/Ipilimumab for Patients With Metastatic Renal Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 18523
  • SECONDARY ID: NCI-2019-00248
  • SECONDARY ID: 18523
  • NCT ID: NCT03829111

Conditions

  • Advanced Renal Cell Carcinoma
  • Clear Cell Renal Cell Carcinoma
  • Metastatic Renal Cell Carcinoma
  • Stage III Renal Cell Cancer American Joint Committee on Cancer AJCC v8
  • Stage IV Renal Cell Cancer American Joint Committee on Cancer AJCC v8
  • Unresectable Renal Cell Carcinoma

Interventions

DrugSynonymsArms
CBM588CBM588; C. butyricum MIYAIRI Strain; C. butyricum MIYAIRI Strain CBM 588, Clostridium butyricum MIYAIRI 588 Probiotic Strain; Clostridium butyricum MIYAIRI 588; MIYAIRI 588; CBM 588, MIYAIRI 588 Strain of C. butyricum; C. butyricum CBM 588 Probiotic Strain; C. butyricum Strain MIYAIRI 588Arm II (CBM588, nivolumab, ipilimumab)
IpilimumabAnti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, YervoyArm I (nivolumab, ipilimumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoArm I (nivolumab, ipilimumab)

Purpose

This phase I trial studies how well CBM588 works when given together with nivolumab and ipilimumab in treating patients with kidney cancer that is stage IV or has spread to other places in the body. CBM588 is a probiotic that may help to increase the effect of immunotherapy. 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. Giving CBM588, nivolumab, and ipilimumab may work better in treating patients with kidney cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the effect of clostridium butyricum CBM 588 probiotic strain (CBM588) (in
      combination with nivolumab/ipilimumab) on the gut microbiome in patients with metastatic
      renal cell carcinoma (mRCC).

      SECONDARY OBJECTIVES:

      I. To evaluate the effect of CBM588 on the clinical efficacy of the nivolumab/ipilimumab
      combination.

      II. To assess the effect of CBM588 on systemic immunomodulation of the nivolumab/ipilimumab
      combination in patients with mRCC.

      III. To assess the effect of CBM588 on toxicities such as diarrhea and nausea using Common
      Terminology Criteria for Adverse Events (CTCAE) version (v) 5 criteria with the
      nivolumab/ipilimumab combination in patients with mRCC.

      OUTLINE: Patients are randomized to 1 of 2 arms.

      ARM I: Patients receive nivolumab intravenously (IV) over 60 minutes and ipilimumab IV over
      60 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of
      disease progression or unacceptable toxicity. Beginning in cycle 5, patients receive
      nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease
      progression or unacceptable toxicity.

      ARM II: Patients receive clostridium butyricum CBM 588 probiotic strain orally (PO) twice
      daily (BID), nivolumab IV over 60 minutes on day 1, and ipilimumab IV over 60 minutes on day
      1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression
      or unacceptable toxicity. Beginning in cycle 5, treatment with clostridium butyricum CBM 588
      probiotic strain and nivolumab repeats every 28 days in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and periodically
      thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (nivolumab, ipilimumab)Active ComparatorPatients receive nivolumab IV over 60 minutes and ipilimumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, patients receive nivolumab IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Ipilimumab
  • Nivolumab
Arm II (CBM588, nivolumab, ipilimumab)ExperimentalPatients receive clostridium butyricum CBM 588 probiotic strain PO BID, nivolumab IV over 60 minutes on day 1, and ipilimumab IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, treatment with clostridium butyricum CBM 588 probiotic strain and nivolumab repeats every 28 days in the absence of disease progression or unacceptable toxicity.
  • CBM588
  • Ipilimumab
  • Nivolumab

Eligibility Criteria

        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

          -  Intermediate or poor risk disease by International Metastatic RCC Database Consortium
             (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

          -  Any ethnicity or race

          -  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)

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (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 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, yogurt or bacterial fortified foods 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

          -  Grade 1 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse
             Events [CTCAE] version [v]4) or baseline 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

          -  White blood cells (WBC) < 2,000/mm^3

          -  Neutrophils < 1,500/mm^3

          -  Platelets < 100,000/mm^3

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x upper limit
             of normal (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)

          -  Serum creatinine > 1.5 x upper limit of normal (ULN)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in Bifidobacterium composition of stool
Time Frame:Baseline up to week 12
Safety Issue:
Description:Will be assessed for patients on both arms.

Secondary Outcome Measures

Measure:Change in Shannon index
Time Frame:Baseline up to week 12
Safety Issue:
Description:Using translational methods, will compute the Shannon index at baseline for a comparison of microbial diversity.
Measure:Best overall response
Time Frame:Up to 2 years
Safety Issue:
Description:Will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST). The association between treatment arm and overall response as per RECIST criteria (response observed versus [vs] not observed) will be examined using Fisher's exact test.
Measure:Progression-free survival (PFS)
Time Frame:From enrollment to progression, assessed up to 2 years
Safety Issue:
Description:The difference in progression free survival across the two groups will be explored graphically using Kaplan-Meier survival plots. Median PFS 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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:City of Hope Medical Center

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