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Advanced Clear Cell Renal Cell CarcinomaPhase 1NCT06399419

CBM588 Capsules in Combination With Nivolumab and Ipilimumab for the Treatment of Advanced Stage Kidney Cancer

A Phase 1 study testing Biospecimen Collection, Bone Scan and CBM588 Capsules in people with Advanced Clear Cell Renal Cell Carcinoma and Advanced Renal Cell Carcinoma, run by Osel, Inc. at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This phase I trial tests the safety, side effects, best dose, and effectiveness of CBM588 in combination with nivolumab and ipilimumab in treating patients with kidney cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Scan and CBM588 Capsules
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteUnited States
Study dates
19 Jun 2024to 19 Oct 2026
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

  • Documented informed consent of the participant and/or legally authorized representative
  • Assent, when appropriate, will be obtained per institutional guidelines
  • Agreement to allow the use of archival tissue from diagnostic tumor biopsies
  • If unavailable, exceptions may be granted with study principle investigator (PI) approval
  • Eastern Cooperative Oncology Group (ECOG) ≤ 2
  • Age ≥ 18 years
Show all 24Show fewer
  • Histologically confirmed renal cell carcinoma with clear cell renal cell carcinoma component or sarcomatoid component
  • Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer [AJCC] stage IV) renal cell carcinoma with intermediate- or poor-risk disease by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria
  • No prior systemic therapy for renal cell carcinoma (RCC) with the following exception:
  • One prior adjuvant or neoadjuvant therapy for completely resectable RCC if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
  • Absolute neutrophil count (ANC) ≥ 1500/uL without granulocyte colony-stimulating factor support
  • White blood cell count ≥ 2500/uL
  • Platelets ≥ 100,000/uL without transfusion
  • Hemoglobin ≥ 8 g/dL
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). ALP ≤ 5 x ULN with documented bone metastases
  • Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN)
  • Serum albumin ≥ 2.8 g/dl
  • Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test < 1.3 x the laboratory ULN
  • Serum calculated creatinine clearance ≥ 50mL/min using the Cockcroft-Gault equation
  • Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of nivolumab for women with childbearing potential, and 7 months after the last dose of nivolumab for men
  • Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes. In addition, females < 55 years-of-age must have a serum follicle stimulating (FSH) level > 40 mIU/mL to confirm menopause).
  • Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site

Who cannot join

  • Prior treatment with ipilimumab and/or nivolumab
  • Current use, or intent to use, probiotics, yogurt, or bacterial fortified foods during the period of treatment
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  • Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
  • 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
  • Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment
Show all 32Show fewer
  • Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
  • Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment
  • Administration of a live, attenuated vaccine within 30 days before first dose of study treatment
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before first dose of study treatment. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted. Adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent are permitted. Transient short-term use of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is also allowed
  • Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness requiring systemic treatments, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active mycobacterial infection
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
  • Malabsorption syndrome
  • Uncompensated/symptomatic hypothyroidism
  • Moderate to severe hepatic impairment (Child-Pugh B or C)
  • Requirement for hemodialysis or peritoneal dialysis
  • History of solid organ or allogenic stem cell transplant
  • Other clinically significant disorders that would preclude safe study participation
  • Any active, known, or suspected autoimmune disease will be excluded, with the following exceptions:
  • Type 1 diabetes mellitus
  • Hypothyroidism only requiring hormone replacement
  • Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment
  • Conditions not expected to recur in the absence of an external trigger
  • Pregnant or lactating females
  • Inability to swallow tablets/capsules or unwillingness or inability to receive IV administration
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded
  • Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
  • Exclusion of subjects with a 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
  • Exclusion of subjects whose baseline pulse oximetry is less than 92% on room air
  • Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

1 site in 1 country.

United States1 site, 1 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Alex Chehrazi-Raffle, MD, 626-218-4772, achehraziraffle@coh.org

    Alex Chehrazi-Raffle, MD

    Recruiting

Other trials in United States

About this study

Official title: An Open-Label, Phase I, Dose-Finding Study of CBM588 in Combination With Nivolumab/Ipilimumab for Patients With Advanced Stage Renal Cell Carcinoma

This phase I trial tests the safety, side effects, best dose, and effectiveness of CBM588 in combination with nivolumab and ipilimumab in treating patients with kidney cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). CBM588 is a live biotherapeutic that may help improve the effects of immunotherapy. Nivolumab and ipilimumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread by enhancing the ability of the body's immune cells to attack tumor cells. CBM588 in combination with nivolumab and ipilimumab may be safe, tolerable, and/or effective in treating patients with advanced stage kidney cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the safety and tolerability of nivolumab/ipilimumab with escalating doses of Clostridium butyricum MIYAIRI 588 capsules (CBM588) in patients with metastatic renal cell carcinoma.

SECONDARY OBJECTIVES:

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

II. To determine the effect of CBM588 (in combination with nivolumab/ipilimumab) in modulation of the gut microbiome in patients with metastatic renal cell carcinoma.

III. To assess the effect of CBM588 on the change of metabolic pathways with the nivolumab/ipilimumab combination in patients with metastatic renal cell carcinoma.

IV. To determine the effect of CBM588 on systemic immunomodulation.

OUTLINE: This is a dose-escalation study of CBM588 followed by a dose-expansion study.

Patients receive CBM588 capsules orally (PO) twice daily (BID) on days 1-21, nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles. Patients then receive CBM588 PO BID on days 1-28 and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT), bone scan and blood sample collection throughout the study. Patients may optionally undergo magnetic resonance imaging (MRI) on study.

After completion of study treatment, patients are followed up once a year.

Being tested
Biospecimen Collection, Bone Scan, CBM588 Capsules, Computed Tomography, Ipilimumab
Medical subject headings
Clear-cell metastatic renal cell carcinoma, Carcinoma, Renal Cell

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone ScanProcedure or surgery

    Also called Bone Scintigraphy

    Undergo bone scan

  • CBM588 CapsulesBiological

    Also called CBM588, Clostridium butyricum MIYAIRI 588, C. butyricum MIYAIRI 588, C. butyricum strain MIYAIRI 588

    Given PO

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • IpilimumabBiological

    Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010

    Given IV

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS-936558, CMAB819

    Given IV

Study groups in NCT06399419
Study groupRoleWhat they receive
Treatment (CBM588 capsules, nivolumab, ipilimumab)ExperimentalPatients receive CBM588 PO BID on days 1-21, nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles. Patients then receive CBM588 PO BID on days 1-28 and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT, bone scan and blood sample collection throughout the study. Patients may optionally undergo MRI on study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Scan; Biological: CBM588 Capsules; Procedure: Computed Tomography; Biological: Ipilimumab; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab

What is being measured

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

  1. Dose limiting toxicity (DLT)

    Toxicities at least possibly related to study agent will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.

    Measured: Up to 28 days

  2. Maximum tolerated dose (MTD)

    MTD estimate will be the highest dose with the occurrence of DLT in no more than 1 out of 6 of the patients.

    Measured: Up to 28 days

  3. Incidence of adverse events (AEs)

    AEs will be graded using CTCAE. Summaries will be provided overall and by dose group. The number and percentage of subjects reporting treatment-emergent AEs (TEAE) will be summarized overall and by the worse CTCAE grade, with a breakdown by dose. The number and percentage of subjects reporting TEAEs considered related to each study drug will be summarized.

    Measured: Up to 3 years

Secondary outcomes (8)

  1. Progression free survival (PFS)

    PFS will be defined as the duration of time from start of treatment to time of progressive disease or death, whichever occurs first. PFS will be estimated using the Kaplan-Meier method. The difference in PFS across dose levels will be explored using the log-rank test. Median PFS time for each dose level will be reported, and the Cox proportional hazard model will be used to estimate the hazard ratio and its confidence interval without adjustment for clinically relevant covariates.

    Measured: From enrollment to progression or death, assessed up to 3 years

  2. Overall response rate (ORR)

    Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The best overall response is the best response recorded from the start of the treatment until disease progression or recurrence. ORR will be calculated as the number of patients with complete or partial response divided by the total number of treated/evaluable subjects. ORR will be summarized by dose levels, number, and percentage, along with corresponding exact 95% confidence interval. The association between dose level and overall response as per RECIST v1.1 criteria will be examined using Fisher's exact test.

    Measured: Up to 3 years

  3. Change in stool microbial diversity

    The Shannon index will be computed from whole metagenome sequence data from stool samples to compare microbial diversity between baseline and 12 weeks and between the two study arms. The index takes into account the number of species (richness) and their relative abundance (evenness). A higher Shannon index indicates greater microbial diversity. The minimum value the Shannon diversity index can take is 0 (one species) and there is no upper limit to the index.

    Measured: Baseline to week 12 of therapy

  4. Change in abundancies of gut microbiome species

    The taxonomic composition of the microbiome will be determined from whole metagenome sequencing of stool samples and the relative abundancies of species will be compared between baseline and 12 weeks and between the two study arms. The relative abundancies will vary from 0 to 1.

    Measured: Baseline to week 12 of therapy

  5. Metabolic pathways

    The abundancies of gut microbiome metabolic pathways will be estimated using whole metagenome sequence data from stool samples. Metabolic pathways with significantly different counts between baseline and week 12 and between the two study arms will be compared.

    Measured: Baseline to week 12 of therapy

  6. Changes in serum short chain fatty acids

    The proportion of serum short chain fatty acids will be estimated using translational methods. The levels (ng/ml) of butyrate and other short chain fatty acids in blood will be assessed graphically over serial timepoints of blood collection to determine trends over time and between study arms.

    Measured: Baseline up to 3 years of therapy

  7. Circulating regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs)

    The proportion of Tregs and MDSCs in the blood will be estimated using flow cytometry methods. The percentage of viable immune cells (from 0%-100%) will be assessed graphically over serial timepoints of blood collection to determine trends over time and between study arms.

    Measured: Baseline up to 3 years of therapy

  8. Serum Cytokines

    The levels (pg/ml) of serum cytokines in blood will be estimated using flow cytometry methods and will include IFN gamma, TNF alpha, IL-2, IL-6, IL-8, IL-10, GM-CSF, and other cytokines/chemokines. The relative levels of cytokines will be assessed graphically over serial timepoints of blood collection to determine trends over time and between study arms.

    Measured: Baseline up to 3 years of therapy

Timeline

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

  1. First posted3 May 2024
  2. Study start19 Jun 2024 (estimated)
  3. Primary completion19 Oct 2026 (estimated)
  4. Study completion19 Oct 2026 (estimated)

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
28 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06399419
Sponsor's protocol ID
23554
Other IDs
NCI-2024-03079, 23554, P30CA033572
Status last verified
May 2024
First submitted
1 May 2024
Last updated
30 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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

  • Tomita Y, Ikeda T, Sakata S, Saruwatari K, Sato R, Iyama S, Jodai T, Akaike K, Ishizuka S, Saeki S, Sakagami T. Association of Probiotic Clostridium butyricum Therapy with Survival and Response to Immune Checkpoint Blockade in Patients with Lung Cancer. Cancer Immunol Res. 2020 Oct;8(10):1236-1242. doi: 10.1158/2326-6066.CIR-20-0051. Epub 2020 Jul 14.

    PubMed 32665261

  • Tomita Y, Goto Y, Sakata S, Imamura K, Minemura A, Oka K, Hayashi A, Jodai T, Akaike K, Anai M, Hamada S, Iyama S, Saruwatari K, Saeki S, Takahashi M, Ikeda T, Sakagami T. Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors. Oncoimmunology. 2022 May 27;11(1):2081010. doi: 10.1080/2162402X.2022.2081010. eCollection 2022.

    PubMed 35655708

  • Tomita Y, Sakata S, Imamura K, Iyama S, Jodai T, Saruwatari K, Hamada S, Akaike K, Anai M, Fukusima K, Takaki A, Tsukamoto H, Goto Y, Motozono C, Sugata K, Satou Y, Ueno T, Ikeda T, Sakagami T. Association of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations. Cancers (Basel). 2023 Dec 21;16(1):47. doi: 10.3390/cancers16010047.

    PubMed 38201474

  • Paz Del Socorro T, Oka K, Boulard O, Takahashi M, Poulin LF, Hayashi A, Chamaillard M. The biotherapeutic Clostridium butyricum MIYAIRI 588 strain potentiates enterotropism of Rorgammat+Treg and PD-1 blockade efficacy. Gut Microbes. 2024 Jan-Dec;16(1):2315631. doi: 10.1080/19490976.2024.2315631. Epub 2024 Feb 22.

    PubMed 38385162

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biospecimen Collection, Bone Scan and CBM588 Capsules in people with Advanced Clear Cell Renal Cell Carcinoma and Advanced Renal Cell Carcinoma, run by Osel, Inc. 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 24 inclusion and 32 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: status not confirmed, as of the sponsor's last update on 30 May 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?

Results are not available in the source record.

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

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity (DLT) (time frame: Up to 28 days). The study lists 3 primary outcomes in all. 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 NCT06399419, which also lists 5 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 30 May 2024.

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