- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04130763
Fecal Microbiota Transplant (FMT) Capsule for Improving the Efficacy of Anti- PD-1
December 7, 2023 updated by: Shen Lin, Peking University
Investigator-initiated Trial of Fecal Microbiota Transplant (FMT) Capsule for Improving the Efficacy of Anti-PD-1 in Patients With PD-1 Resistant Digestive System Cancers
To determine whether the fecal microbiota transplant (FMT) capsule can help reverse the resistance of anti-PD-(L)1 treatment in Gastrointestinal (GI) cancer patients.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
This study is designed to improve the response rate of anti-PD-(L)1 among patients with anti-PD-(L)1 resistant/refractory digestive (including gullet, stomach and intestine) system cancers through the intervention on their gut microbiota.
Healthy people who have the gut microbiota profile similar to the responders of anti-PD-(L)1 therapy will be identified.
The gut microbiota of these healthy people will be extracted to product FMT capsule.
Gastrointestinal (GI) cancer patients who failed anti-PD-(L)1 treatment will be administrated with anti-PD-1 immunotherapy combined with FMT.
The enrolled subjects will firstly receive 1-week of FMT therapy.
Subsequently, each anti-PD-1 treatment will be combined with the maintenance dose of FMT capsules to ensure the efficiency of gut microbiota colonization.
Each subject will receive anti-PD-1 therapy for 6 cycles.
After the completion of both 3 and 6 cycles of therapy, safety and efficacy assessments will be conducted.
The subjects who complete 3 cycles of treatment but are clinically evaluated as disease progression will not continue to the following 3 cycles of treatment.
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Beijing
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Beijing, Beijing, China, 100142
- Beijing Cancer Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Patient had a histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumors originating from the GI tract.
- Patient was able and willing to provide pathological tissue embedded in wax blocks or paraffin sections.
- Patient had received any number of radiation therapy, chemotherapy, vaccine therapy or other oncological therapy are permitted.
- Patient was receiving or has received at least 2-dose injections of systemic PD-(L)1 immunotherapy, and imaging results confirmed progressive disease (PD). According to iRECIST, PD is defined as an increase in the length of the lesion > 20% or occurrence of new lesion or non-target lesion progression. Anti-PD-(L)1 drugs can contain pembrolizumab, nivolumab or any other anti-PD-(L)1 drugs that have passed phase 2 clinical development. Patients are eligible when the previous failed anti-PD-1 treatment was initiated within one year of the first dose of this trial.
- Patient was willing and able to swallow at least 20 FMT capsules.
- Patient was willing and able to sign the informed consent form.
- Patient consented to receive follow-up medical imaging to determine disease progression and provide stool samples before and after taking capsules at each follow-up visit.
- Patient was at least 18 years old, male or female.
- Patient had an ECOG performance of 0 or 1.
- For women with childbearing potential, the results of blood pregnancy test within 7 days prior to enrollment or the results of urine pregnancy test within 72 hours prior to enrollment had to be negative.
- Patient must have had basic body function. Blood test results needed to reach the following indexes: Absolute neutrophil count (ANC)≥1500/mcL, platelets≥100,000/mcL, hemoglobin≥9 g/dL or 5.6 mmol/L, no transfusion or EPO dependency (within 7 days of assessment), serum creatinine≤1.5×upper limit of normal (ULN) or creatinine clearance≥60 mL/min, serum total bilirubin≤1.5×ULN or direct bilirubin≤ULN, AST (SGOT) and ALT (SGPT)≤2.5×ULN for patients with serum total bilirubin >1.5 ULN or ≤5×ULN for patients with liver metastases, albumin≥2.5 mg/dL, coagulation indexes INR or PT ≤1.5×ULN. Unless patient was receiving anticoagulant therapy, coagulation indexes were within normal range of therapy.
- Expected survival duration ≥3 months.
Exclusion Criteria:
- Patient with irritable bowel syndrome, toxic megacolon, and severe dietary allergies (including severe allergic to shellfish, nuts, seafood).
- Patient had responded to anti-PD-(L)1 therapy or had a stable disease status (per iRECIST at CR, PR, or SD).
- Patient had participated in any other clinical trial within 4 weeks before the first dose of FMT capsule treatment.
- Patient had highly severe symptoms including rapidly declining ECOG performance; rapidly worsening symptoms; lesion transferring to critical sites and requiring urgent medical intervention.
- Patient had a known history of malignant blood diseases, primary brain tumor or sarcoma, or other primary solid tumors except gastrointestinal tumors.
- Patient had progressing CNS metastases or leptomeningeal metastases. Patients with stable brain metastases had to be re-screened by brain MRI brain or CT scan within two weeks before enrollment to ensure no disease progression, and simultaneously take ≤10mg steroid daily one week prior to treatment. Patients with no history of CNS metastases or no signs of CNS metastases did not need another medical imaging examination for brain diseases.
- Patient had a severe hypersensitivity or reaction to anti-PD-(L)1 immunotherapy.
- Patient had an autoimmune disease or a history of autoimmune disease or required treatment with systemic steroid (prednisone >10 mg daily or equivalent dose of similar drugs) or immunosuppressive agents. The following cases were exceptions: local, ophthalmic, intra-articular, intranasal, or inhaled corticosteroids with extremely low systemic absorption; hormone replacement therapy; short-term (≤7 days) treatment of corticosteroids for preventative use (e.g., allergy to contrast agents).
- Patient had pneumonitis or had a history of (non-infectious) pneumonitis requiring steroid therapy.
- Patient had severe cardiovascular disease (e.g., drug-uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, severe obstructive or restrictive pulmonary diseases, or systemic infections.
- Patient had active human immunodeficiency virus (HIV) infection (performance as HIV 1/2 antibodies and/or positive).
- Patient had active Hepatitis B (HBV) or Hepatitis C (HCV) infection.
- Patient had known active tuberculosis.
- Patient had received a live vaccine or live attenuated vaccine within 4 weeks prior to enrollment.
- Patient had reported adverse events (per CTCAE 5.0, ≥grade 2) due to drug treatment within 4 weeks and not recovered from it. Patients who had undergone major surgery had to have completely recovered from toxicity and complications of previous interventions prior to participating in the study.
- Patient had received anti-tumor therapy except experimental drugs (e.g., chemotherapy, targeted small molecule therapy or radiotherapy) within 2 weeks prior to screening or planned to receive anti-tumor therapy except experimental drugs (e.g., chemotherapy, targeted small molecule therapy or radiotherapy) during the study period. Radiotherapy used for pain control was an exception.
- Patient had a known history of psychiatric or drug abuse.
- Patient was pregnant or breastfeeding, or subjects (including male subject and his female spouse) could not take effective contraceptive measures at the time of signing the informed consent until 120 days after the final anti-PD-1 therapy combined with FMT treatment.
- Patient could not stop antibiotics treatment 24 hours before administration due to infection, etc.
- Other cases that investigators qualified as relevant for patients who could not participate in the study, e.g., any medical history, treatment history, or history of abnormal test data that possibly confuses the study results, or interferes with patients' participation in the whole study, or damages patient interests.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: FMT Capsule in Combination with Anti-PD-1 Therapy
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FMT capsules administration starts in the first week of enrollment.
Capsules are taken for three consecutive days in the first week.
From week 2, anti-PD-1 therapy will be administrated in combination with the maintenance dose of FMT treatment once every two weeks for up to 6 times.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: 14 weeks
|
Number of subjects with objective responses (Complete Response (CR) + Partial Response (PR)) divided by total number of subjects, per iRECIST.
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14 weeks
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Rate of abnormal vital signs and laboratory test results
Time Frame: 1 weeks
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Rate of abnormal vital signs and laboratory test results that are determined to be clinically significant prior to the first anti-PD-1 immunotherapy treatment.
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1 weeks
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The number of adverse events
Time Frame: 1 weeks
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The number of grade 2 or above adverse events that is related to FMT prior to the first anti-PD-1 immunotherapy treatment.
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1 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Function of T-cells
Time Frame: 14 weeks
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Compare the changes in cells expressing IFN-γ before and after treatment between response subjects and non-response subjects (per iRECIST).
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14 weeks
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Association of anti-PD-1 response with gut microbiota
Time Frame: 14 weeks
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Compare the changes in bacterial abundance and bacterial diversity before and after treatment between response subjects and non-response subjects (per iRECIST).
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14 weeks
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Rate of abnormal vital signs, physical examination results, 12-lead electrocardiogram and laboratory test results
Time Frame: 14 weeks
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Rate of abnormal vital signs, physical examination results, 12-lead electrocardiogram and laboratory test results that are determined to be clinically significant from the beginning of the first anti-PD-1 immunotherapy treatment to the end of study.
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14 weeks
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The number of adverse events
Time Frame: 14 weeks
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The number of grade 2 or above adverse events that is related to FMT from the beginning of the first anti-PD-1 immunotherapy treatment to the end of study.
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14 weeks
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Change in T-cells Composition
Time Frame: 14 weeks
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Compare the changes in CD8+PD-1+T cells, Ki67+CD8+ T cells before and after treatment between response subjects and non-response subjects (evaluated by iRECIST).
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14 weeks
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Change in subsets of specific and non-specific immune system
Time Frame: 14 weeks
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Compare the changes in T-cell receptor diversity (quantified by immune repertoire sequencing analyses), CD8+CCR7+CD45RA+T cells, CD4+CCR7+CD45RA+ T cells and CD4 + Foxp3 + T cells before and after treatment between response subjects and non-response subjects (evaluated by iRECIST).
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14 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Lin Shen, MD, Peking University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 5, 2019
Primary Completion (Actual)
February 1, 2023
Study Completion (Estimated)
January 31, 2024
Study Registration Dates
First Submitted
October 13, 2019
First Submitted That Met QC Criteria
October 15, 2019
First Posted (Actual)
October 17, 2019
Study Record Updates
Last Update Posted (Estimated)
December 13, 2023
Last Update Submitted That Met QC Criteria
December 7, 2023
Last Verified
December 1, 2023
More Information
Terms related to this study
Other Study ID Numbers
- XBI-302CT1001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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