Microbiota Transplant to Cancer Patients Who Have Failed Immunotherapy Using Faeces From Clinical Responders

NCT05286294 | Active Not Recruiting Phase 2 DMC

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

Brief Summary

This is a single-arm, single-center, open-label, phase IIa study evaluating the safety, feasibility and efficacy of Faecal Microbiota Transplant (FMT) to cancer patients not responding to ICI therapy, using ICI-responders as donors.

Conditions

Melanoma Stage IV; Head and Neck Squamous Cell Carcinoma; Cutaneous Squamous Cell Carcinoma; MSI-High; Clear Cell Renal Cell Carcinoma; Non-small Cell Lung Cancer

Keywords

Fecal microbiotal transplant (FMT); Immunotherapy

Outcome Measures

Primary Outcomes (2)

• Safety evaluation of Fecal Microbiota Transplant (FMT) in advanced cancer patients

  Safety of the intervention (FMT) as assessed by the incidence, nature, and severity of Adverse Events (AE) according to NCI CTCAE, version 5.0

  10 years

• Tumor response evaluation

  Objective Tumor Response Rate (ORR) as assessed by iRECIST in FAS

  10 years

Secondary Outcomes (11)

• Feasibility evaluation of FMT for advanced cancer patients

  10 years

• Overall survival (OS)

  10 years

• Objective Tumor Response Rate (ORR)

  10 years

• Progression Free Survival (PFS)

  10 years

• Durable response rate (DRR)

  10 years

Other Outcomes (4)

• Immunological response evaluation

  10 years

• Explorative assessment of biomarkers or clinical responses and toxicity

  10 years

• Investigation of T cell reactivity to neoantigens and microbial antigens

  10 years

Study Arms (1)

Treatment

EXPERIMENTAL

Fecal Microbiota Transplant (FMT)

Biological: Fecal Microbiota Transplant (FMT)

Interventions

Fecal Microbiota Transplant (FMT) BIOLOGICAL

Fecal Microbiota Transplant (FMT)

Treatment

Eligibility Criteria

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

You may qualify if:

• Participant must be 18 years of age, at the time of signing the informed consent
• Histologically confirmed malignant melanoma, NSCLC, CSCC, HNSCC, renal clear cell carcinoma or MSI+ solid cancer
• Metastatic disease or local recurrence not curable by standard therapy
• PD-L1 positivity is required for subjects with HNSCC (\>20% combined positive score) and NSCLC (\>20% PD-L1 expression)
• Measurable disease according to iRECIST
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Progressive disease, as considered by the treating physician, on therapy with PD1/PD-L1 blockers and/or CTLA4-blockers and/or LAG-3 blockers, or combinations regimes comprising any of these agents. Further treatment with ICI is considered to be within standard practice.
• Patients without any response to ICI at any time point during their disease history are eligible, without a need for re-introduction of ICI before enrollment, even if subsequent lines of anti-cancer therapy have been given. For patients with prior response to ICI, the criteria depend on the cancer form:
• Malignant melanoma, NSCLC and MSI-H/dMMR solid cancers: Prior response to ICI is allowed only if PD under ICI has been documented \<9 months before enrolment and without subsequent lines of anti-cancer therapy. For patients with prior response to ICI followed by subsequent lines of anti-cancer therapy, and patients that have not received ICI the last 9 months, ICI has to be re-introduced, and these patients have to again show progressive disease while on ICI therapy.
• CSCC, HNSCC and renal clear cell carcinoma: Prior response to ICI is allowed, without a need for re-introduction, even if subsequent lines of anti-cancer therapy have been given, provided that disease progression has been documented under ICI therapy the last 12 months.
• Mandatory pre-FMT biopsy and lesion accessible for further biopsies
• Life expectancy \>3 months
• Adequate organ function as defined below:
• Hemoglobin \> 9 g/dL
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L

You may not qualify if:

• Other cancer within 3 years prior to study entry, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer)
• Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \> 2 weeks prior to first FMT
• Uncontrolled pleural effusion, pericardial effusion, or ascites. Patients with indwelling catheters are allowed
• Uncontrolled tumor-related pain. Patients requiring narcotic pain medication must be on a stable regimen at study entry. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrolment. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not presently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrolment.
• Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to study entry, unstable arrhythmias, or unstable angina. Patients with a known left ventricular ejection fraction (LVEF) \< 40% will be excluded. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF \< 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate
• Undergone allogeneic stem cell or solid organ transplantation
• A positive test for HIV
• Active hepatitis B (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HbsAg test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
• Active tuberculosis
• Ongoing immune-related adverse effects from immunotherapy treatments that are of Grade ≥2, excluding endocrine adverse effects. An ongoing grade 2 cutaneous reaction is allowed.
• Severe infection within 14 days prior to first FMT, requiring hospitalization.
• Any condition that significantly increases the risk of perforation during endoscopy for FMT.
• A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
• Known psychiatric or substance abuse disorders that would interfere with cooperation and the requirements of the trial
• A requirement of systemic antibiotics at the time of study entry.

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, 0379, Norway

Location

MeSH Terms

Conditions

Melanoma; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Jon Amund Kyte, MD, Ph.D.

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: March 18, 2022
• Study Start: June 28, 2022
• Primary Completion (Estimated): March 31, 2034
• Study Completion (Estimated): December 31, 2034
• Last Updated: July 3, 2025

Record last verified: 2025-06

Locations

NO (1)