Phase 1 study of Disulfiram and Nivolumab for gastric cancer

JRCT ID: jRCTs031180183

Registered date:05/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Gastric cancer
• Date of first enrollment: 03/04/2019
• Target sample size: 16
• Study type: Interventional

Intervention(s)

Disulfiram (po): 160mg three times daily (480mg/day) or 80mg three times daily (240mg/day) for maximum 6 cycles.
Nivolumab (iv): 240mg every 2 weeks for maximum 6 cycles.
1 cycle is for 28 days.

Outcome(s)

• Primary Outcome: Rate of DLT (dose limiting toxicities) expression
• Secondary Outcome: Progression-free survival (PFS), Response rate (RR), Duration of response (DOR), Percentage of subjects treated with surgical resection after chemotherapy(complete resection), Percentage of subjects with adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Patients with histologically or cytologically confirmed advanced/recurrent gastric cancer after previous chemotherapy
2) Patients without previous treatment with anti-PD1/PDL1 inhibitor.
3) Patients with at least one measurable lesion based on the Response Evaluation Criteria in Solid Tumors (RECIST) guideline ver.1.1.
4) Patients who are aged more than 20 years at the time of informed consent.
5) Patient with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6) Patients with adequate oral intake
7) Patients with adequate organ functions as determined by laboratory test values measured within 7 days before enrollment in the study (laboratory testing on the same day of the week at 7 days before enrollment was permitted).
a) Neutrophils: more than 1200/mm3
b) Platelets: more than 75,000/mm3
c) Hemoglobin: more than 8.5 g/dL
d) Total bilirubin: less than or equal to 1.5 mg/dL
e) AST: less than or equal to 100 U/L (with liver metastasis, less than or equal to 150 U/L)
f) ALT: less than or equal to 100 U/L (with liver metastasis, less than or equal to 150 U/L)
g) Creatinine: less than or equal to 1.5 mg/dL or creatinine clearance using the Cockcroft-Gault equation of more than 40 mL/min
8) Patients who have recovered from a previous treatment regimen with a toxicity level lower than CTCAE Grade 1. The following symptoms were excluded: hair loss, peripheral sensory neuropathy, excessive skin pigmentation, and dysgeusia.
9) Patients who have not received a transfusion or hematopoietic factors, such as granulocyte colony-stimulating factor (G-CSF), within 7 days prior to enrollment.
10) Patients who have agreed to use appropriate contraceptive methods during the study period and 6 months after cessation of the test drug. Premenopausal female patients who have a possibility of becoming pregnant should have had a negative urine pregnancy test within 7 days prior to enrollment.
Contraception methods approved or certified in Japan should be used, including condoms, a pessary, an intrauterine contraceptive device (IUD), implant contraceptive devices (currently there are no approved such devices in Japan), vasectomy, and tubal ligation.
Menopause: Defined as the time during which there are no menstrual periods for more than 1 year after the last menstrual period and no other medical reasons for menorrhea have been identified.
11) Patients who are expected to survive more than 3 months from the date of the initial administration of the clinical drug.
12) Written informed consent has been obtained from the patient for participation in this study

Exclude criteria

1) Patients with a primary tumor of the central nervous system or symptomatic or progressive central nervous system metastasis. If no growth and symptoms were observed during more than past 2 months, the patient is eligible
2) Patients with acquired immunodeficiency syndrome or with active autoimmune diseases
3) Patients who have received treatments, such as chemotherapy, radiotherapy, or other any other drug under trial, within 2 weeks prior to enrollment in the study.
4) Patients who have received treatments with cancer therapeutic vaccines; genetically modified viruses, such as oncolytic virus therapy; or genetically modified cell therapy within 4 weeks prior to enrollment in the study.
5) Patients who had received live vaccination within 30 days before protocol treatment
6) Patients with active infectious diseases requiring systemic treatment.
7) Patients with clinical symptoms or image findings consistent with those of interstitial pneumonia or pulmonary fibrosis.
8) Patients who were HIV-1 antibody-positive, HBs antigen-positive, or HCV antibody-positive.
9) Patients with severe cardiovascular disease that met criteria III or higher of the New York Heart Association [NYHA] classification for congestive heart failure within 6 months prior to enrollment in the study, unstable angina, or a history of myocardial infarction or complication of serious arrhythmia.
10) Patients who require steroid (glucocorticoid) treatment or other immunosuppressants.
11) Patients with poorly controlled diabetes mellitus.
12) Patients who can not withdraw from alcohol drinking, medications, foods and cosmetics containing alcohol
13) Pregnant or lactating patients. If breastfeeding, even if breastfeeding is interrupted, patients cannot be enrolled.
14) Patients who have difficulty adhering to scheduled visits, treatment plans, clinical laboratory testing, or other study procedures.
15) Patients whom the investigator considers would influence the assessment or safety of the test drug or the interpretation of the results.

Related Information

• Primary Sponsor: Shitara Kohei
• Secondary Sponsor: Matsuhisma Kouji
• Source(s) of Monetary Support: AMED