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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04130763
Recruitment Status : Recruiting
First Posted : October 17, 2019
Last Update Posted : August 12, 2020
Sponsor:
Information provided by (Responsible Party):
Shen Lin, Peking University

Brief Summary:
To determine whether the fecal microbiota transplant (FMT) capsule improves the response rate of anti-PD-1 treatment.

Condition or disease Intervention/treatment Phase
Gastrointestinal System Cancer Biological: FMT capsule Phase 1

Detailed Description:
This study is designed to improve the response rate of anti-PD-1 among patients with anti-PD-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-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-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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 3, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bowel Movement

Arm Intervention/treatment
Experimental: FMT Capsule in Combination with Anti-PD-1 Therapy Biological: FMT capsule
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.




Primary Outcome Measures :
  1. 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.

  2. Rate of abnormal vital signs and laboratory test results [ Time Frame: 1 weeks ]
    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.

  3. The number of adverse events [ Time Frame: 1 weeks ]
    The number of grade 2 or above adverse events that is related to FMT prior to the first anti-PD-1 immunotherapy treatment.


Secondary Outcome Measures :
  1. Change in T-cells Composition [ Time Frame: 14 weeks ]
    Compare the changes in CD8 + PD1+ T cells, Ki67+PD-1+CD8+T cells before and after treatment between response subjects and non-response subjects (per iRECIST).

  2. Change in subsets of specific immune system [ Time Frame: 14 weeks ]
    Compare the changes in CD8+ 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 (per iRECIST).

  3. Change in subsets of non-specific immune system [ Time Frame: 14 weeks ]
    Compare the changes in CD56 + NK cells and CD68+ cells before and after treatment between response subjects and non-response subjects (per iRECIST).

  4. Function of T-cells [ Time Frame: 14 weeks ]
    Compare the changes in cells expressing IFN-γ before and after treatment between response subjects and non-response subjects (per iRECIST).

  5. Association of anti-PD-1 response with gut microbiota [ Time Frame: 14 weeks ]
    Compare the changes in bacterial abundance and bacterial diversity before and after treatment between response subjects and non-response subjects (per iRECIST).

  6. Rate of abnormal vital signs, physical examination results, 12-lead electrocardiogram and laboratory test results [ Time Frame: 14 weeks ]
    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.

  7. The number of adverse events [ Time Frame: 14 weeks ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients have a histologically or cytologically confirmed diagnosis of unresectable or metastatic solid tumors originating from the GI tract.
  2. Patients are able and willing to provide pathological tissue embedded in the wax blocks or paraffin sections.
  3. Patients who have received any number of radiation therapy, chemotherapy, vaccine therapy or other oncological therapy are permitted.
  4. Patients are currently receiving or have received at least 2-dose injection of systemic PD-1 immunotherapy. The results of hospital imaging examination were confirmed as 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-1 drugs contain pembrolizumab, nivolumab or any other anti-PD-1 drugs that haspassed 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.
  5. Patients are willing and able to swallow at least 20 FMT capsules.
  6. Patients must be willing and able to sign the informed consent form.
  7. Patients consent to receive follow-up medical imaging to determine disease progression, and provide stool samples before and after taking capsules at each follow-up visit.
  8. Patients must be at least 18 years old, regardless male or female..
  9. Patients need to have basic physical movement with ECOG scale of 0 or 1.
  10. 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 must be negative.
  11. Patients must have basic body function. Blood test results need 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 is receiving anticoagulant therapy, coagulation indexes should be within normal range of therapy.
  12. Expected survival duration≥3 months.

Exclusion Criteria:

  1. Patients with irritable bowel syndrome, toxic megacolon, severe dietary allergies (including severe allergic to shellfish, nuts, seafood).
  2. Patients who have responded to anti-PD-1 therapy or are in stable disease status (per iRECIST).
  3. Patients are participating in any other clinical trial within 4 weeks before the first dose of FMT capsule treatment.
  4. Patients with highly severe symptom (including rapidly declining on ECOG performance; rapidly worsening symptoms; lesion transferring to critical sites and requiring urgent medical intervention).
  5. Patients have a known history of malignant blood diseases, has a primary brain tumor or sarcoma, or other primary solid tumors except digestive system tumors.
  6. Has progressing CNS metastases or leptomeningeal metastasis. Patients with stable brain metastases must 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 before study beginning. Patients with no history of CNS metastases or no signs of CNS metastases do not need another medical imaging examination for brain diseases.
  7. Had a severe hypersensitivity reaction to anti-PD-1 immunotherapy.
  8. Has an autoimmune disease or a history of autoimmune disease or requires treatment of systemic steroid (prednisone >10 mg daily or equivalent dose of similar drugs) or immunosuppressive agents. The following cases are excepted: local, ophthalmic, intra-articular, intranasal, or inhaled corticosteroids with extremely low systemic absorption, hormone replacement therapy, short-term (≤7 days) treatment of corticosteroids for preventive use (e.g., allergy to contrast agents).
  9. Currently has pneumonitis or a history of (non-infectious) pneumonitis that required steroid therapy.
  10. Has 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, systemic infections.
  11. Has active human immunodeficiency virus (HIV) infection (performance as HIV 1/2 antibodies and/or positive).
  12. Has active Hepatitis B (HBV) or Hepatitis C (HCV) infection.
  13. Has known active tuberculosis.
  14. Has received a live vaccine or live attenuated vaccine within 4 weeks prior to enrollment.
  15. Has appeared adverse events (per CTCAE 5.0, ≥grade 2) due to drug treatment within 4 weeks and not recovered from it. Patients who have undergone major surgery must have completely recovered from toxicity and complications of previous interventions before study beginning.
  16. Has received anti-tumor therapy except experimental drugs (e.g., chemotherapy, targeted small molecule therapy or radiotherapy) within 2 weeks before screening or plans 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 controlling is excepted.
  17. Has known history of psychiatric or drug abuse.
  18. Patient is pregnant or breastfeeding, or subjects (including male subject and his female spouse) cannot take effective contraceptive measures from signing the informed consent to 120 days after the final anti-PD-1 therapy combined with FMT treatment.
  19. Patients who cannot stop antibiotics treatment 24 hours before administration due to infection, etc.
  20. Other cases that investigators think patients cannot 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04130763


Contacts
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Contact: Lin Shen 86-10-88196561 linshenpku@163.com

Locations
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China, Beijing
Beijing Cancer Hospital Recruiting
Beijing, Beijing, China, 100142
Contact: Lin Shen    86-10-88196561    linshenpku@163.com   
Sponsors and Collaborators
Peking University
Investigators
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Principal Investigator: Lin Shen, MD Peking University
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Responsible Party: Shen Lin, MD, Professor, Chief of Department of GI Oncology, Beijing Cancer Hospital, Peking University
ClinicalTrials.gov Identifier: NCT04130763    
Other Study ID Numbers: XBI-302CT1001
First Posted: October 17, 2019    Key Record Dates
Last Update Posted: August 12, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shen Lin, Peking University:
Immuno-checkpoint inhibitor therapy
GI cancer
FMT