Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Papillary Renal Cell Carcinoma

Chromophil Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

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.

Cabozantinib S-malate

Clostridium butyricum CBM 588 Probiotic Strain

Sumanta K Pal

This phase I trial evaluates the effects of CBM588 in combination with standard therapies, nivolumab and cabozantinib, in treating patients with kidney cancer that has spread to other places in the body (advanced/metastatic). The digestive microbiome may have an effect on how patients respond to treatment, and previous research shows that a specific bacteria found in the gut (Bifidobacterium) may predispose participants to a better response to standard therapies. CBM588 is a strain of bacteria that can restore species of Bifidobacterium to the microbiome. The primary aim of this study is to determine how CBM588 changes the microbiome of patients with metastatic renal cell carcinoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving CBM588, nivolumab, and cabozantinib may kill more tumor cells.

PRIMARY OBJECTIVE:

I. To determine the effect of clostridium butyricum CBM 588 probiotic strain (CBM588) (in combination with cabozantinib/nivolumab) in modulation of 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 cabozantinib/nivolumab combination.

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

OUTLINE: Patients are randomized to 1 of 2 arms.

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

ARM 2: Patients receive CBM588 PO twice a day (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.

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

CBM588 in Combination With Nivolumab and Cabozantinib for the Treatment of Advanced or Metastatic Kidney Cancer

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

Will be assessed for patients' stool sample

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

Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The association between treatment arm and overall response as per RECIST criteria (response observed versus not observed) will be examined using Fisher's exact test.

The difference in progression free survival across the two groups will be explored graphically using Kaplan-Meier survival plots. Median progression-free survival 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.

Using translational methods will estimate the proportion of T-cells in the blood. This will be assessed graphically across serial timepoints of blood collection to ascertain any trends. Will compare the proportion of circulating T-cells with cabozantinib/nivolumab alone versus cabozantinib/nivolumab with CBM 588.

Using translational methods will estimate the proportion of MDSCs in the blood. This will be assessed graphically across serial timepoints of blood collection to ascertain any trends. Will compare the proportion of circulating MDSCs with cabozantinib/nivolumab alone versus cabozantinib/nivolumab with CBM 588.

Using translational methods will estimate the proportion of serum cytokines in the blood. This will be assessed graphically across serial time points of blood collection to ascertain any trends. Will compare the IL-6, IL-8, and other cytokines/chemokines with cabozantinib/nivolumab alone versus cabozantinib/nivolumab with CBM 588.

Will compare toxicities, such as diarrhea and nausea, using Common Terminology Criteria for Adverse Events version 5 with cabozantinib/nivolumab alone versus cabozantinib/nivolumab with CBM 588.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CBM588 in Combination With Nivolumab and Cabozantinib for the Treatment of Advanced or Metastatic Kidney Cancer	NCT05122546	Advanced Clear ... Advanced Papill... Advanced Renal ... Advanced Sarcom... Metastatic Clea... Metastatic Papi... Metastatic Rena... Metastatic Sarc... Stage III Renal... Stage IV Renal ... Unresectable Cl... Unresectable Re...	Cabozantinib S-... Clostridium but... Nivolumab	18 Years -	City of Hope Medical Center
CBM588 in Combination With Nivolumab and Cabozantinib for the Treatment of Advanced or Metastatic Kidney Cancer	NCT05122546	Advanced Clear ... Advanced Papill... Advanced Renal ... Advanced Sarcom... Metastatic Clea... Metastatic Papi... Metastatic Rena... Metastatic Sarc... Stage III Renal... Stage IV Renal ... Unresectable Cl... Unresectable Re...	Cabozantinib S-... Clostridium but... Nivolumab	18 Years -	City of Hope Medical Center
CBM588 in Combination With Nivolumab and Cabozantinib for the Treatment of Advanced or Metastatic Kidney Cancer	NCT05122546	Advanced Clear ... Advanced Papill... Advanced Renal ... Advanced Sarcom... Metastatic Clea... Metastatic Papi... Metastatic Rena... Metastatic Sarc... Stage III Renal... Stage IV Renal ... Unresectable Cl... Unresectable Re...	Cabozantinib S-... Clostridium but... Nivolumab	18 Years -	City of Hope Medical Center

Spots Global Cancer Trial Database for advanced papillary renal cell carcinoma