Fecal Microbiota Transplant (FMT) Capsule for Improving the Efficacy of Anti- PD-1

NCT04130763 | Completed Phase 1 DMC

• 1 other identifier: XBI-302CT1001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastrointestinal System Cancer

Keywords

Immuno-checkpoint inhibitor therapy; GI cancer; FMT

Outcome Measures

Primary Outcomes (3)

• Objective Response Rate (ORR)

  Number of subjects with objective responses (Complete Response (CR) + Partial Response (PR)) divided by total number of subjects, per iRECIST.

  14 weeks

• The number of adverse events

  The number of adverse events that is related to FMT prior to the first anti-PD-1 immunotherapy treatment.

  1 week

• Rate of abnormal vital signs and laboratory test results

  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.

  1 week

Secondary Outcomes (6)

• Change in T-cells Composition

  14 weeks

• Function of T-cells

  14 weeks

• Association of anti-PD-1 response with gut microbiota

  14 weeks

• Rate of abnormal vital signs, physical examination results, 12-lead electrocardiogram and laboratory test results

  14 weeks

• Change in subsets of specific and non-specific immune system

  14 weeks

Study Arms (1)

FMT Capsule in Combination with Anti-PD-1 Therapy

EXPERIMENTAL

FMT Capsule in Combination with Anti-PD-1 Therapy

Biological: FMT capsule

Interventions

FMT capsule BIOLOGICAL

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.

FMT Capsule in Combination with Anti-PD-1 Therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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-(L)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.

You may not qualify if:

• 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 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 and 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.

Sponsors & Collaborators

• Peking University: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Lin Shen, MD

  Peking University

  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: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor, Chief of Department of GI Oncology, Beijing Cancer Hospital

Study Record Dates

• First Submitted: October 13, 2019
• First Posted: October 17, 2019
• Study Start: December 5, 2019
• Primary Completion: February 1, 2023
• Study Completion: January 29, 2024
• Last Updated: September 24, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)