Preventing Toxicity in Renal Cancer Patients Treated With Immunotherapy Using Fecal Microbiota Transplantation

NCT04163289 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: PERFORM Renal
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Cancer immunotherapy has been largely adopted in oncology patient management in the last decade. The deep and long responses to immunotherapy have accelerated the approval of these drugs across multiple disease sites. However, these agents can also be toxic to patients, meaning, the patient will have to discontinue treatment and outcomes could be negatively affected. Recently, a combination of two immunotherapy drugs, ipilimumab and nivolumab (ipi/nivo), has been approved for the treatment of intermediate and poor-risk renal cell carcinoma (RCC) patients. This powerful combination provides survival benefit, however, it can also be highly toxic leading to discontinuation of this treatment. There has been some evidence that these otherwise toxic drugs can be better tolerated by altering the composition of the patients gut bacteria to create a more diverse and healthy microbiome. The current study will involve Fecal Microbiota Transplantation (FMT) before the start of the immunotherapy combination, and during the first two cycles of ipilimumab treatment (the more toxic agent) as supportive therapy to prevent toxicity associated with the ipi/nivo combination. The goal of this project is to study the safety of such FMT combination treatment and reduce occurrence of immune-related toxicities in patients, allowing them to continue their cancer treatments in the hopes of a better outcome. The investigators will also be looking at changes in the immune populations, microbiome profile of patients, response to treatment, and patient survival as secondary objectives.

Conditions

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Occurence of immune-related colitis associated with ipilimumab/nivolumab treatment

  Occurence of grade 3 or higher immune-related colitis from the start of treatment with ipilimumab and nivolumab to 120 days after completion of treatment. Colitis will be graded using the Common Toxicity Criteria for Adverse Events version 4.02.

  28 months

Secondary Outcomes (7)

• Incidence of any immune-related adverse event associated with ipilimumab/nivolumab treatment

  28 months

• Proportion of patients who discontinue treatment because of immune-related adverse events

  28 months

• Objective response rate

  Approximately 9 years (end of study)

• Changes in patient microbiome following FMT

  At baseline (prior to FMT) and prior to the 1st, 2nd, 3rd and fourth dose of immunotherapy (approximately 1 week, 3 weeks, 7 weeks , and 10 weeks post FMT).

• Success rate of the fecal microbiota transplant

  At baseline (prior to FMT) and prior to the 1st, 2nd, 3rd and fourth dose of immunotherapy (approximately 1 week, 3 weeks, 7 weeks , and 10 weeks post FMT).

Other Outcomes (3)

• Progression-free survival

  Approximately 7 years

• Overall survival

  Approximately 7 years

• Assess the immune profile of the tumor

  At baseline (prior to FMT) and between weeks 7 and 10.

Study Arms (1)

Fecal Microbiota Transplantation

EXPERIMENTAL

Fecal microbiota transplantation combined with approved standard of care treatment with nivolumab and ipilimumab.

Drug: Fecal Microbiota Transplantation

Interventions

Fecal Microbiota Transplantation DRUG

Fecal microbiota transplantation is the process of administering stool samples derived from healthy donors, which have been processed and prepared into capsules. Capsules will be taken 7 days or more prior to the first treatment with nivolumab and ipilimumab, and 1 to 3 days prior to the next 2 treatments with nivolumab and ipilimumab.

Fecal Microbiota Transplantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed diagnosis of advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) renal cell carcinoma
• Intermediate or poor risk RCC as defined by International Metastatic RCC Database Consortium (IMDC criteria, Heng et al 2009):
• Karnofsky performance status (KPS) \< 80%
• Less than 1 year form initial RCC diagnosis (including original localized disease if applicable) to systemic treatment
• Hemoglobin \< lower limit of normal (LLN)
• Corrected calcium \> 10 mg/dL
• Absolute neutrophil count (ANC) \> upper limit of normal (ULN)
• Platelet count \> ULN
• Age ≥ 18 years.
• Karnofsky Performance Status (KPS) ≥70%
• Evaluable disease determined by the Investigator
• Ability to ingest capsules
• Able to provide written informed consent
• Understand non-infectious risks associated with FMT administration and that the long term data regarding safety risks of FMT are lacking
• Recovery to baseline or ≤ Grade 1 CTCAE v 4.0 from toxicities related to any prior treatments, unless AEs are clinically non-significant

You may not qualify if:

• Prior systemic therapy for unresectable locally advanced or metastatic RCC including investigational agents.
• Radiation therapy for bone metastasis within 2 weeks, or any other radiation therapy within 4 weeks prior to study entry. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible for the study.
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with signing the informed consent through 6 months after FMT.
• Diagnosis of immunodeficiency (e.g. HIV, transplantation)
• Receiving systemic steroid therapy (\>10mg prednisone daily or equivalent) or any other form of immunosuppressive therapy prior to trial treatment. Adrenal replacement steroids doses \> 10 mg daily prednisone equivalent are permitted. Transient short-term use of systemic steroids for allergic situations (e.g. contrast allergy) is also permitted. Patients who require inhaled, intranasal, intra-articular, or topical steroids are allowed. Intermittent use of bronchodilators or local steroid injections are not excluded from the study
• Ongoing use of antibiotics or previous use of antibiotics in the last two weeks prior to the initial FMT procedure
• Presence of a chronic intestinal disease (e.g. Celiac, malabsorption, colonic tumor)
• Presence of absolute contra-indications to FMT administration
• Toxic megacolon
• Severe dietary allergies (e.g. shellfish, nuts, seafood)
• Inflammatory bowel disease
• Expected to require any other form of systemic or localized anti-neoplastic therapy while on study. Treatment with either bisphosphonate or denosumab for bone metastatic disease is allowed
• Known history of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the patient has undergone potentially curative therapy with no evidence of that disease for five years
• o NOTE: This time requirement also does not apply to patients who underwent successful definitive resection of basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cancers including cervical cancer, breast cancer, melanoma, or other in situ cancers.
• Active central nervous system (CNS) metastases and/or leptomeningeal involvement, unless treated with radiotherapy and/or radiosurgery with stable disease for at least 4 weeks prior to study entry after radiotherapy or at least 8 weeks prior to study entry after major surgery

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• Academic Medical Organization of Southwestern Ontario: collaborator

Study Sites (1)

London Regional Cancer Program of the Lawson Health Research Institute

London, Ontario, N6A 5W9, Canada

Location

Related Publications (3)

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

• Fernandes R, Jabbarizadeh B, Rajeh A, Hong MMY, Baines KJ, Ernst S, Winquist E, Ali AS, Penny S, Figueredo R, Parvathy SN, Lenehan JG, Pinto DM, Silverman MS, Maleki Vareki S. Fecal microbiota transplantation plus immunotherapy in metastatic renal cell carcinoma: the phase 1 PERFORM trial. Nat Med. 2026 Jan 28. doi: 10.1038/s41591-025-04183-8. Online ahead of print.

  PMID: 41606120 DERIVED

• Ninkov M, Schmerk CL, Moradizadeh M, Parvathy SN, Figueredo R, Burton JP, Silverman MS, Fernandes R, Maleki Vareki S, Haeryfar SMM. Improved MAIT cell functions following fecal microbiota transplantation for metastatic renal cell carcinoma. Cancer Immunol Immunother. 2023 May;72(5):1247-1260. doi: 10.1007/s00262-022-03329-8. Epub 2022 Nov 18.

  PMID: 36396738 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Ricardo Fernandes, MD

  London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

  PRINCIPAL INVESTIGATOR

• Saman Maleki, PhD

  London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2019
• First Posted: November 14, 2019
• Study Start: January 23, 2020
• Primary Completion: November 28, 2023
• Study Completion (Estimated): November 1, 2028
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)