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