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NCCH2308 Safety study of intestinal microbiota following combination therapy with fecal microbial transplantation and antibiotics for patietnts with esophageal cancer and gastric cancer treated with immune checkpoint Inhibitors

Intestinal microbiota transplantation therapy combined with antibiotics for esophageal and gastric cancer patients using immune checkpoint inhibitors (BioRichi2)

Shoji Hirokazu

National Cancer Center Hospital

5-1-1, Tsukiji, Chuo-ku, Tokyo

hshouji@ncc.go.jp

Shoji Hirokazu

National Cancer Center Hospital

5-1-1, Tsukiji, Chuo-ku, Tokyo

+81-3-3542-2511

hshouji@ncc.go.jp

Recruiting

June. 18, 2024

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

Inclusion criteria for patients
1)Histologically diagnosed as esophageal squamous cell carcinoma or gastric adenocarcinoma.
2)Unresectable advanced or recurrent esophageal cancer or gastric cancer.
3)The patient is capable of oral intake.
4)Age at the time of consent is 18 years or older.
5)ECOG-PS:0-1.
6)Have at least one measurable lesion on contrast-enhanced CT within 28 days prior to enrollment.
7)The administration of anti-PD-1 antibodies (Nivolumab, Pembrolizumab) and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody (Ipilimumab) for the treatment of unresectable advanced or recurrent esophageal or gastric cancer is scheduled.
8)Laboratory tests performed within 14 days prior to enrollment meet the criteria. However, the patient must not have received granulocyte colony stimulating factor (G-CSF product) administration or blood transfusion within 14 days prior to blood collection.
1 Neutrophil count >= 1500 /mm3
2 Platelet count >= 10x104 /mm3
3 Hemoglobin >= 8.0 g/dL
4 AST (GOT) =< 100 U/L (=< 200 U/L if liver metastases are present)
5 ALT (GPT) =< 100 U/L (=< 200 U/L if liver metastases are present)
6 Total bilirubin =< 1.5 mg/dL
7 Creatinine =< 1.5 mg/dLor creatinine clearance >=40 ml/min (Cockcroft-Gault estimation formula or 24-hour urine collection)
9)For female of childbearing potential, have agreed to dual contraception, prohibition of egg donation and prohibition of breast feeding from the time of consent until at least 6 months after the last dose of any investigational drug. For male, have agreed to dual contraception and prohibition of sperm donation from the start of investigational drug administration until at least 6 months after the last dose of any investigational drugs.
10)Written consent to participate in the study has been obtained from the patient.

Inclusion criteria for donors
1) Healthy persons who are 18 years of age or older at the time of obtaining consent.
2) Persons who can donate stool regularly.
3) Persons who can undergo a medical interview and screening tests (blood test, stool test, and saliva test) on a regular basis
4) Persons who have the capacity to consent and can obtain written consent of their own free will.

Exclusion criteria for patients
1)The patient has an active overlapping cancer.
2)Patients who are severely allergic to the medications utilized in this study.
3)Patients with HER2 postive.
4)Patients with chronic bowel disease and inflammatory bowel disease.
5)Active autoimmune disease or autoimmune disease requiring systemic steroids or immunosuppressive agents.
6)Receiving systemic corticosteroids or immunosuppressive drugs within 14 days prior to enrollment.
7)Receiving systemic cytotoxic therapy within 14 days prior to enrollment.
8)Receiving systemic molecular targeted therapy within 21 days prior to enrollment.
9)Receiving more than 50 Gy of radiation therapy within 28 days prior to registration. However, in the case of irradiation of less than 50 Gy for bone metastases, irradiation was performed within 14 days prior to enrollment in the study.
10)Received a live vaccine within 4 weeks prior to prior to enrollment.
11)Active infection requiring systemic treatment.
12)Positive for HIV antibody, HBs antigen, or HCV antibody.
13)HBs antigen negative, HBs or HBc antibody positive, and HBV-DNA quantification positive.
14)No severe ascites on CT imaging that extends beyond the pelvic cavity to the upper abdomen. No massive ascites or pleural effusion requiring drainage.
15)Patients who are judged to be unsuitable as research subjects by the principal investigator (co-investigator)

Donor exclusion criteria
1)Those who are suspected of having a health problem or risk based on an interview regarding their health condition, medical hist
ory, treatment history, vaccination history, high-risk behaviors (piercing, needle sticks, unspecified sexual contact), and travel hi
story.
2)Those who are suspected of being infected with or carrying the following pathogenic viruses, bacteria, or parasites:
Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis E virus, HIV-1,2, HTLV-1, cytomegalovirus, EB virus, syphilis, Myc
obacterium tuberculosis, Clostridioides difficile, intestinal tract Hemorrhagic E. coli (O-157), enteroaggregative E. coli (EAEC), e
nteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), Shiga toxin-producing E. coli (STEC), enteroinvasive E. coli (EI
EC), Salmonella, Shigella, Yersinia, Campylobacter, Vibrio parahaemolyticus, Vibrio cholerae, Vibrio vulnificus, Plesiomonas shi
gelloides, drug-resistant bacteria, adenovirus, norovirus, rotavirus, astrovirus, sapovirus, SARS-CoV-2, parasites (Strylcoccus n
ematodes, Giardia triumphalis, Cryptosporidium, Entamoeba histolytica, Cyclospora, and other insect eggs and bodies)
3)Those whose blood test results deviate from standard values for general peripheral blood tests, creatinine, C-reactive protein, A
ST, ALT, ALP, total bilirubin, and albumin.
4)Those whose fecal hemoglobin test results are positive for fecal occult blood (for women, the test is performed outside the men
strual period)
5)Those who are judged to be unsuitable as research subjects by the research director (sub-researcher)

Both

Unresectable advanced or recurrent esophageal cancer or gastric cancer

1) Three types of antibiotics (amoxicillin, fosfomycin, metronidazole) will be administered for one week.
1. For amoxicillin, administer 1,500 mg of amoxicillin hydrate orally in 3 divided doses per day.
2. For fosfomycin, administer 3,000 mg of fosfomycin calcium hydrate orally in 3 divided doses per day.
3.Metronidazole is administered orally at 750 mg in 3 divided doses per day.
2)Administer 200mL of intestinal flora solution once through colonoscopy.
3) Start administering a regimen containing ICI from the day after FMT.

Esophageal cancer, gastric cancer

Fecal Microbiota Transplantation

treatment limiting toxicity incidence rate

Response rate, Disease control rate, Progression-free survival, Overall Survival, Adverse event rate, Biomarkers

+81-3-3542-2511

May. 23, 2024

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