Clinical Trials /

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

NCT04130763

Description:

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

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Ampulla of Vater Carcinoma
  • Esophageal Carcinoma
  • Gastrointestinal Stromal Tumor
  • Malignant Esophagogastric Neoplasm
  • Malignant Gastric Neoplasm
  • Malignant Intestinal Neoplasm
  • Malignant Small Intestinal Neoplasm
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: XBI-302CT1001
  • NCT ID: NCT04130763

Conditions

  • Gastrointestinal System Cancer

Interventions

DrugSynonymsArms
FMT capsuleFMT Capsule in Combination with Anti-PD-1 Therapy

Purpose

To determine whether the fecal microbiota transplant (FMT) capsule improves the response rate of anti-PD-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. Specifically, we will find healthy
      people that have the intestine similar to patients with Gastrointestinal (GI) system cancer
      who has responded to anti-PD-1 therapy, extract the gut microbiota of these healthy people to
      product FMT capsule, and then perform re-anti-PD-1 immunotherapy combined with FMT for GI
      system cancer patients whose anti-PD-1 treatment failed.
    

Trial Arms

NameTypeDescriptionInterventions
FMT Capsule in Combination with Anti-PD-1 TherapyExperimental
  • FMT capsule

Eligibility Criteria

        Inclusion Criteria:

          -  1. Patients have a histologically or cytologically confirmed diagnosis of unresectable
             stage III or IV solid tumors originating in the GI tract.

             2. Patients are able and willing to provide pathological tissue embedded in the wax
             blocks or paraffin sections.

             3. Patients have received radiation therapy, chemotherapy, vaccine therapy or other
             systemic therapies for tumors are permitted.

             4. Patients are currently receiving systemic PD-1 immunotherapy or have received
             anti-PD-1 immunotherapy. Anti-PD-1 drugs contain pembrolizumab, nivolumab or any other
             anti-PD-1 drugs passed clinical phase 2. Combination treatment of Ipilimumab and
             anti-PD-1 immunotherapy are not included.

             5. The results of hospital imaging examination were confirmed as progressive disease
             (PD) after patients received at least 2-dose injection of anti-PD-1 immunotherapy.
             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. Once PD is confirmed,
             the confirming date will be considered as the initiate date of disease progression.
             Patients are eligible within a year after the initiation of anti-PD-1 therapy.

             6. Patients with CNS metastasis (not leptomeningeal metastasis) are eligible if CNS
             metastases are treated and deemed stable (with a repeat CT/ MRI imaging study) prior
             to the enrollment date. If patients had radiotherapy to treat CNS metastasis, patients
             should begin this study at least 2 weeks after radiotherapy.

             7. Patients must be willing and able to take 5 doses of FMT capsules. Each dose
             contains 16 capsules and can be taken several times.

             8. Patients must be willing and able to sign the informed consent form. 9. Patients
             consent to receive follow-up medical imaging to determine disease progress, and
             provide stool samples before and after taking capsules and at each follow-up visit.

             10. Patients must be at least 18 years old on the date of enrollment. No gender
             limitation.

             11. Patients need to have basic physical movement with ECOG scale of at least 0 or 1.

             12. Female patients with childbearing potential need to collect urine for pregnancy
             test within 72 hours prior to the first day of treatment. Pregnant patients are not
             eligible.

             13. Patients with fertility potential must be willing to use serious methods of
             contraception during the study until 120 days after the last anti-PD1 treatment.

             14. Patients must have basic body function. Blood test results need to reach the
             following indexes: Absolute neutrophil count (ANC)≥1500/mcL, platelets≥100000/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.

        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 had stable diseases (per
             IRECIST).

             3. Patients are participating in any other clinical trial now or within 4 weeks before
             the first 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) are not eligible.

             5. Patients need to receive any other form of systemic antineoplastic therapy such as
             radiation therapy, chemotherapy and etc. while on study.

             6. Patients are diagnosed with immunodeficiency or is receiving systemic steroid
             therapy (>10 mg daily) or any other form of immunosuppressive therapy prior to trial
             treatment. Patients receiving physiological steroid therapy at a daily dose ≤10mg are
             permitted to enroll.

             7. 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.

             8. 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 taken ≤10mg
             steroid daily one week before study beginning. Patients with leptomeningeal disease
             are not eligible. Patients with no history of CNS metastases or no signs of CNS
             metastases do not need another medical imaging examination for brain diseases.

             9. Had a severe hypersensitivity reaction to treatment with anti-PD-1 therapy. 10. Has
             an autoimmune disease or a history of autoimmune disease or syndrome that requires
             treatment of systemic steroid or immunosuppressive agents. Patients with vitiligo,
             type I diabetes, resolved childhood asthma/specific reaction are exceptions to this
             rule. Patients who require intermittent use of bronchodilators or local steroid
             injections are not excluded from the study. Patients with hypothyroidism stable on
             hormone replacement are not excluded from the study.

             11. Currently has pneumonitis or a history of (non-infectious) pneumonitis that
             required steroid therapy.

             12. Has severe cardiovascular disease (e.g., drug-uncontrolled congestive heart
             failure, hypertension, cardiac ischemia, myocardial infarction, and severe cardiac
             arrhythmia), bleeding disorders, autoimmune diseases, severe obstructive or
             restrictive pulmonary diseases, systemic infections, or irritable bowel syndrome.

             13. Has an active systemic infection requiring systemic therapy. 14. Has active human
             immunodeficiency virus (HIV) infection (performance as HIV 1/2 antibodies and/or
             positive).

             15. Has active Hepatitis B (HBV) or Hepatitis C (HCV) infection. Patients who have
             recovered after receiving anti-viral therapy may be considered for enrollment after
             discussion with Principal Investigator.

             16. Has a known history of active bacillary phthisis. 17. Has received a live vaccine
             within 4 weeks prior to the first dose of treatment. Note: General inactivated
             influenza vaccine for injection do not influence the enrollment; however intranasal
             influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.

             18. Has appeared adverse events due to drug treatment within 4 weeks and not recovered
             from it.

             19. Has received chemotherapy, targeted small molecule therapy or radiotherapy within
             two weeks before study beginning, or has not recovered from adverse events due to the
             pre-administered agents. Patients with ≤ 2 level neuropathy are exception of this
             criteria and permitted to participate in this study. Patients who have undergone major
             surgery must have completely recovered from the toxicity and complications of previous
             interventions before study beginning.

             20. Has any history of disease, 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 damage patients' interests.

             21. Has known history of psychiatric or drug abuse and will interfere patients who
             cooperate with this trial.

             22. Patient is pregnant or breastfeeding, or male or female patients plan for
             pregnancy within the duration of the trial until 120 days after study ending.

             23. Has taken antibiotics within 30 days before first treatment due to infection, etc.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:14 weeks
Safety Issue:
Description:Number of patients with objective responses (Complete Response (CR) + Partial Response (PR)) divided by total number of patients, per iRECIST.

Secondary Outcome Measures

Measure:Change in T-cells Composition
Time Frame:14 weeks
Safety Issue:
Description:Compare the changes in CD8 + PD1+ T cells, Ki67+PD-1+CD8+T cells (measured by percent of total cells) and MFI (staining intensity) before and after treatment between response patients and non-response patients (per iRECIST).
Measure:Change in subsets of specific immune system
Time Frame:14 weeks
Safety Issue:
Description: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 patients and non-response patients (per iRECIST).
Measure:Change in subsets of non-specific immune system
Time Frame:14 weeks
Safety Issue:
Description:Compare the changes in CD56 + NK cells and CD68+ cells before and after treatment between response patients and non-response patients (per iRECIST).
Measure:Function of T-cells
Time Frame:14 weeks
Safety Issue:
Description:Compare the changes in cells (measured by percent of total cells) expressing IFN-γ and MFI (fluorescence intensity) before and after treatment between response patients and non-response patients (per iRECIST and irRECIST).
Measure:Association of anti-PD-1 response with gut microbiota
Time Frame:14 weeks
Safety Issue:
Description:Compare the changes in bacterial abundance (quantified by the operational taxonomic unit (OTU) which indicates the number of different species present along with the representative proportion of each species in the sample) and bacterial diversity (quantified by alpha diversity which is defined by the Shannon Index and quantifies both the organismal richness of a sample and the evenness of the organisms' abundance distribution) before and after treatment between response patients and non-response patients (per iRECIST).
Measure:Safety evaluation (from the beginning of the first anti-PD-1 immunotherapy treatment to the end of study)
Time Frame:14 weeks
Safety Issue:
Description:The safety of FMT capsule by ways of assessing adverse events.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Peking University

Trial Keywords

  • Immuno-checkpoint inhibitor therapy
  • GI cancer
  • FMT

Last Updated

October 15, 2019