What side effects are associated with this type of intervention?

Common treatments for Renal Cell Carcinoma, such as nivolumab (an immunotherapy) and cabozantinib (a tyrosine kinase inhibitor), have several known side effects. Nivolumab can cause immune-related adverse effects including fatigue, rash, diarrhea, and liver enzyme abnormalities. Cabozantinib's side effects often include hypertension, diarrhea, fatigue, and hand-foot syndrome. The combination of these therapies may increase the risk of these side effects. Additionally, the investigational use of CBM588 aims to restore gut microbiota, which could potentially influence the overall side effect profile, but specific data on this is still under investigation.

What prior FDA approvals exist?

The FDA has approved several treatments for Renal Cell Carcinoma (RCC), including immunotherapy and tyrosine kinase inhibitors (TKIs). Nivolumab, a PD-1 checkpoint inhibitor, and cabozantinib, a VEGF inhibitor, are both FDA-approved for advanced RCC. These drugs are part of the standard treatment regimens and are being studied in combination with CBM588, which aims to restore Bifidobacterium species in the gut microbiome to potentially enhance treatment efficacy. Other FDA-approved treatments for RCC include pembrolizumab (another PD-1 inhibitor), axitinib, sunitinib, pazopanib, and lenvatinib, which target various pathways involved in tumor growth and immune evasion.

What other types of research exist?

Promising alternatives to CBM588 for Renal Cell Carcinoma patients could include other probiotics such as Bifidobacterium pseudocatenulatum CECT 7765, which has shown efficacy in modulating metabolic and immune responses. Additionally, exploring other strains of Bifidobacterium or Lactobacillus that have demonstrated anti-inflammatory and immune-modulating properties could be beneficial. Further research into synbiotics (combinations of probiotics and prebiotics) may also offer novel therapeutic options.

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Tyrosine Kinase Inhibitor

CBM588 + Nivolumab + Cabozantinib for Kidney Cancer

Phase 1

Waitlist Available

Led By Sumanta K Pal

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Absolute neutrophil count (ANC) >= 1500/uL without granulocyte colony-stimulating factor support (within 14 days before first dose of study treatment)

Karnofsky performance status >= 70%

Must not have

Active ILD/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a special bacteria (CBM588) with two cancer drugs in patients with advanced kidney cancer. The bacteria might help the drugs work better by changing gut bacteria. The drugs help the immune system fight cancer and stop cancer growth.

Who is the study for?

Adults with advanced or metastatic kidney cancer who haven't had systemic therapy for it, except possibly one prior treatment if the cancer came back after at least 6 months. They should have a certain level of blood cells and organ function, not be pregnant, agree to use contraception, and can't have severe illnesses that would make the trial unsafe for them.

What is being tested?

The trial is testing CBM588 (a probiotic strain) combined with nivolumab (an immune system booster) and cabozantinib (a cell growth blocker), to see if they work better together against kidney cancer that has spread. It's in phase I to check how this combo affects patients' gut bacteria and their response to treatment.

What are the potential side effects?

Possible side effects include typical reactions from immunotherapy like fatigue, skin issues, or inflammation in organs; digestive changes due to the probiotic; plus liver problems or high blood pressure from cabozantinib. Each patient may experience different side effects.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My white blood cell count is healthy without needing medication.

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I am able to care for myself but may not be able to do active work.

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My kidney cancer cannot be cured with surgery or radiation and has spread.

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My white blood cell count is healthy without needing medication.

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I am not pregnant and cannot become pregnant.

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My kidney function, measured by creatinine levels or clearance, is within the required range.

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My kidney cancer has spread to other parts of my body.

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My kidney cancer has been confirmed and includes specific types.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have or had lung inflammation treated with steroids.

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I have no other active cancers or any diagnosed within the last 3 years needing treatment.

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I cannot swallow pills or receive treatments through an IV.

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I have been treated with cabozantinib before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Bifidobacterium composition of stool

Secondary study objectives

Best overall response

Change in proportion of circulating myeloid-derived suppressor cells (MDSC)

Comparison of IL-6, IL-8 and other cytokines/chemokines

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm 2 (CBM588, nivolumab, cabozantinib S-malate)Experimental Treatment3 Interventions

Patients receive CBM588 PO BID, nivolumab IV over 30 minutes on day 1, and cabozantinib S-malate PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (nivolumab, cabozantinib S-malate)Active Control2 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib S-malate PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Clostridium butyricum CBM 588 Probiotic Strain

2019

Completed Phase 1

~30

Nivolumab

2015

Completed Phase 3

~4010

Cabozantinib S-malate

2013

Completed Phase 2

~590

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Renal Cell Carcinoma (RCC) include immune checkpoint inhibitors like nivolumab, which enhance the immune system's ability to target cancer cells, and tyrosine kinase inhibitors (TKIs) like cabozantinib, which block enzymes that promote tumor growth and angiogenesis. The trial involving CBM588, which restores beneficial Bifidobacterium species in the gut microbiome, suggests that microbiome modulation can potentially improve the efficacy of these treatments. This multifaceted approach is important for RCC patients as it combines immune activation, inhibition of tumor growth pathways, and microbiome health to optimize treatment outcomes.

Stool Bacteriomic Profiling in Patients with Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor-Tyrosine Kinase Inhibitors.Current management and future perspectives of metastatic renal cell carcinoma.The future of tyrosine kinase inhibitors: single agent or combination?