The safety and efficacy of oral cancer vaccine B440

JRCT ID: jRCT2051220143

Registered date:27/12/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced urothelial carcinoma
• Date of first enrollment: 19/01/2023
• Target sample size: 12
• Study type: Interventional

Intervention(s)

Oral administration once a day of B440 800mg or 1600mg with fasting for 5 days, followed by 2 days off for 7 days as 1 course, total 4 consecutive courses (4 weeks, 20 times oral administration).
An interval of oral adoministration is 20 hours or more between adomistrations.

Outcome(s)

Primary Outcome

Presence or absence of DLT
(Until Day 28 after the start of drug administration)

Secondary Outcome

Safety
1. Presence or absence of adverse events
2. Serum IL-6 level
Efficacy
1. Presence or absence of response as best overall response
2. Progression free survival (PFS)
Exploratory
Immunological parameters
1. Confirmation of WT1 protein-specific T cell response
a. ELISPOT assay
b. Intracellular cytokine staining
c. Cytokine multiitem simultaneous quantification
2. Confirmation of CD8 T cell induction specific to WT1 epitopes in peripheral blood
(Tetramer assay HLA-A*02:01 RMFPNAPYL or HLA-A*24:02 CYTWNQMNL, and not performed if HLA is neither type)
3. Bacterial composition of the intestinal flora
Microbiome metagenomic analysis using next-generation sequencing
4. Fecal organic acids and short-chain fatty acids
Fecal physicochemical analysis
5. Confirmation of WT1 protein expression in tumor cells
Immunohistological examination of WT1 antigen protein

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 85age old
• Gender: Both

Include criteria

1. Be willing and able to provide written informed consent for the adequate explanation of this trial.
2. Age between 18 and 85 at the time of informed consent.
3. Have histologically confirmed urothelial carcinoma.
4. Have urothelial carcinoma resistant or intolerant to PD-1/PD-L1 inhibitors.
5. Have unresectable urothelial carcinoma refractory or intolerant to standard treatment (including Enfortumab vedotin).
6. General condition is 0 or 1 in Performance Status (PS) based on ECOG (Eastern Cooperative Oncology Group).
7. Have at least 1 measurable lesion (including lymph node lesion) based on RECIST (Response Evaluation Criteria in Solid Tumors) ver1.1 that has not been irradiated.
8. The test value within 14 days before registration satisfies all the following test criteria. In addition, it is conditional that the blood transfusion has not been performed within 14 days (including same day of the week) before the examination.
a. Neutrophil count 1.5 x10^3/microL or more
b. Hemoglobin 8.0g/dL or more
c. Platelet count 75 x10^3/microL or more
d. Total bilirubin 1.5mg/dL or less
e. AST (GOT) 100 U/L or less, ALT (GPT) 100 U/L or less
f. Serum creatinine 1.5mg/dL or less, or calculated creatinine clearance (Cockcroft-Gault formula) 50mL/min or more
g. SpO2 93 percent or more
9. Adverse events associated with prior treatment have resolved to Grade 1 or less in CTCAE (Common Terminology Criteria for Adverse Events) v5.0-JCOG (Japan Clinical Oncology Group); or Grade 2 or higher symptoms (hair loss, peripheral sensory neuropathy, skin hyperpigmentation, dysgeusia) are stable.

Exclude criteria

1. Has been administered anticancer drugs and other therapeutic drugs within 28 days before registration.
2. Has an infection requiring systemic treatment.
3. Has serious complications (intestinal paralysis, intestinal obstruction, pulmonary fibrosis, uncontrolled diabetes, heart failure, myocardial infarction, angina pectoris, renal failure, liver failure, psychiatric disease, cerebrovascular disease, ulcer required transfusion, etc.).
4. Has history or complication of interstitial pneumonia requiring treatment.
5. Has severe mental disorder.
6. Pregnant, possibly pregnant diagnosed by doctor interview etc, or breast-feeding* (* Breast-feeding who discontinue breastfeeding will not be enrolled in this study)
7. There is no intention of contraception in the subject or his/her partner from the start of administration of B440 to the specified period* (* Male: a period from the start of the drug administration to 180 days after the last dose of the drug, Female who may become pregnant: a period from the start of the drug administration to 154 days after the last dose of the drug).
8. A subject of childbearing potential who is unable to perform a pregnancy test at screening.
9. Has a history of severe drug allergy.
10. Positive for either HBs antigen or HCV antibody in a test within 6 months before the enrollment.
11. Positive for HIV antibody in past tests.
12. Be receiving continuous systemic administration (oral or intravenous) of steroids or other immunosuppressive agents (except for immune-related adverse events caused by immune checkpoint inhibitors).
13. Has complication of autoimmune disease or history of chronic or recurrent autoimmune disease (except immune-related adverse events caused by immune checkpoint inhibitors).
14. Has a history of hypersensitivity to the ingredients of this drug and bifidobacteria protein.
15. Be judged by the investigator or subinvestigator to be inappropriate to participate in this study.

Related Information

• Primary Sponsor: Teishima Jun
• Secondary Sponsor: Shirakawa Toshio
• Source(s) of Monetary Support: Immunorock Co., Ltd.