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Advanced Renal Cell CarcinomaPhase 1NCT03829111

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

A Phase 1 study testing Clostridium butyricum CBM 588 Probiotic Strain, Ipilimumab and Nivolumab in people with Advanced Renal Cell Carcinoma and Clear Cell Renal Cell Carcinoma, run by City of Hope Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Clostridium butyricum CBM 588 Probiotic Strain, Ipilimumab and Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
14 May 2019to 13 Dec 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Be willing and able to provide informed consent for the trial
  • 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
Show all 15Show fewer
  • 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

Who cannot join

  • 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
  • Not recovered to =< grade 1 toxicities related to any prior therapy before administration of study drug
  • 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
Show all 20Show fewer
  • 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
  • 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
  • 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)
  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Pilot Study to Evaluate the Biologic Effect of CBM588 in Combination With Nivolumab/Ipilimumab for Patients With Metastatic Renal Cell Carcinoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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 30 minutes and ipilimumab IV over 30 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 30 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 30 minutes on day 1, and ipilimumab IV over 30 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.

Being tested
Clostridium butyricum CBM 588 Probiotic Strain, Ipilimumab, Nivolumab
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Clostridium butyricum CBM 588 Probiotic StrainDrug

    Also called C. butyricum CBM 588 Probiotic Strain, C. butyricum MIYAIRI Strain, C. butyricum Strain MIYAIRI 588, CBM 588

    Given PO

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4

    Given IV

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

Study groups in NCT03829111
Study groupRoleWhat they receive
Arm I (nivolumab, ipilimumab)Active comparatorPatients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 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 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Ipilimumab; Biological: Nivolumab
Arm II (CBM588, nivolumab, ipilimumab)ExperimentalPatients receive clostridium butyricum CBM 588 probiotic strain PO BID, nivolumab IV over 30 minutes on day 1, and ipilimumab IV over 30 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.
Receives: Drug: Clostridium butyricum CBM 588 Probiotic Strain; Biological: Ipilimumab; Biological: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Bifidobacterium composition of stool

    Will be assessed for patients on both arms.

    Measured: Baseline up to week 12

Secondary outcomes (3)

  1. Change in Shannon index

    Using translational methods, will compute the Shannon index at baseline for a comparison of microbial diversity.

    Measured: Baseline up to week 12

  2. Best overall response

    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.

    Measured: Up to 2 years

  3. Progression-free survival (PFS)

    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.

    Measured: From enrollment to progression, assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Feb 2019
  2. Study start14 May 2019
  3. Primary completion13 Dec 2023
  4. Study completion13 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03829111
Sponsor's protocol ID
18523
Other IDs
NCI-2019-00248, 18523, P30CA033572
Status last verified
Jul 2024
First submitted
1 Feb 2019
Last updated
3 Jul 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Villemin C, Six A, Neville BA, Lawley TD, Robinson MJ, Bakdash G. The heightened importance of the microbiome in cancer immunotherapy. Trends Immunol. 2023 Jan;44(1):44-59. doi: 10.1016/j.it.2022.11.002. Epub 2022 Dec 1.

    PubMed 36464584

  • Dizman N, Meza L, Bergerot P, Alcantara M, Dorff T, Lyou Y, Frankel P, Cui Y, Mira V, Llamas M, Hsu J, Zengin Z, Salgia N, Salgia S, Malhotra J, Chawla N, Chehrazi-Raffle A, Muddasani R, Gillece J, Reining L, Trent J, Takahashi M, Oka K, Higashi S, Kortylewski M, Highlander SK, Pal SK. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nat Med. 2022 Apr;28(4):704-712. doi: 10.1038/s41591-022-01694-6. Epub 2022 Feb 28.

    PubMed 35228755

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Clostridium butyricum CBM 588 Probiotic Strain, Ipilimumab and Nivolumab in people with Advanced Renal Cell Carcinoma and Clear Cell Renal Cell Carcinoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Bifidobacterium composition of stool (time frame: Baseline up to week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03829111, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.

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