Treatment of Advance Gastric Cancer With Disulfiram

Clinical Study of Disulfiram Combined With Cisplatin in the Treatment of Advanced Gastric Cancer

Chemotherapy is generally needed for advanced gastric cancer, and cisplatin is the main chemotherapy drug. However, there are many adverse reactions, including bone marrow suppression, gastrointestinal reactions, renal toxicity and neurotoxicity. These adverse reactions can affect the comfort and compliance of patients during treatment. At present, it is necessary to reduce adverse reactions of cisplatin and increase the chemotherapy sensitivity of gastric cancer to cisplatin. Recent studies have found that disulfiram has a potential anti-tumor effect. The disulfiram has shown significant in vivo and in vitro anti-tumor activity in preclinical studies, and has become a potential candidate drug for tumor treatment as an adjuvant in various clinical trials. In this clinical study, cisplatin combined with disulfiram is mainly used to treat advanced gastric cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Chemotherapy；Advanced Gastric Cancer；Cisplatin；Disulfiram
• Intervention / Treatment: Drug: disulfiram and cisplatin; Drug: cisplatin

Detailed Description

Chemotherapy is generally needed for advanced gastric cancer, and cisplatin is the main chemotherapy drug. However, there are many adverse reactions, including bone marrow suppression, gastrointestinal reactions, renal toxicity and neurotoxicity. These adverse reactions can affect the comfort and compliance of patients during treatment. At present, it is necessary to reduce adverse reactions of cisplatin and increase the chemotherapy sensitivity of gastric cancer to cisplatin. Recent studies have found that disulfiram has a potential anti-tumor effect. The disulfiram has shown significant in vivo and in vitro anti-tumor activity in preclinical studies, and has become a potential candidate drug for tumor treatment as an adjuvant in various clinical trials. In this clinical study, cisplatin combined with disulfiram is mainly used to treat advanced gastric cancer.Subjects were randomized in a 1:1 ratio, one group being the control group and the other group being the observation group. Control group: On the first day of treatment, the patients were given intravenous drip of 80mg/m2 cisplatin, 21 days as a course of treatment, lasting for six courses. Observation group: On the first day of treatment, the patients were given intravenous drip of 80mg/m2 cisplatin, 21 days as a course of treatment, lasting for six courses. Disulfiram 400mg was given orally daily and continued until the end of the chemotherapy course. Based on the patient's tolerance to disulfiram, the disulfiram dose may be reassessed during treatment with a minimum oral dose of 125mg per day. The clinical symptoms, signs and adverse reactions were observed in the patients, and the treatment effect was evaluated after three weeks as a cycle and two cycles.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hongzhang Shen; Phone Number: 057156005600; Email: sakshen@126.com
• Study Contact Backup: Name: Xiaofeng Zhang; Phone Number: 057156005600

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Hangzhou First People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

1. Inclusion criteria: ① Age ≥18 years old; ② Gastric cancer is confirmed through gastroscopy biopsy; ③ The patient meets the relevant diagnostic criteria in People's Republic of China (PRC) Health Industry Standards: Diagnostic Criteria for Gastric Cancer, and has reached the level of stage III and IV futures, and the patient refuses to receive surgical treatment; ④ Estimated survival time > 3 months; ⑤ Without any chemotherapy treatment or more than one month from the end of the last chemotherapy course; ⑥Karnofsky functional status score ≥ 60;
2. Exclusion criteria: ① patients who had allergic reaction to therapeutic drugs; ② patients with other types of cancer; ③ Patients with severe diseases of heart, liver, kidney, etc.; (4) gastrointestinal dysfunction or unable to oral medication.
3. Shedding/eliminating criteria: exiting in the midway; Lost to follow-up during the follow-up period; Treatment was not continued according to the treatment protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: disulfiram and cisplatin; Cisplatin combined with disulfiram chemotherapy	Drug: disulfiram and cisplatin; on the first day of treatment, patients were given intravenous drip of 80mg/m2 cisplatin, and 21 days was a course of treatment, lasting for 6 courses. Take 400mg disulfiram orally every day, and continue to use it until the end of chemotherapy. According to the patient's tolerance to disulfiram, the dose of disulfiram can be re-evaluated during the treatment, and the lowest dose is 125mg per day. The clinical symptoms, signs and adverse reactions of patients were observed, and the treatment effect of patients was evaluated after two consecutive cycles with 3 weeks as a cycle.
Active Comparator: standard cisplatin; Cisplatin chemotherapy alone	Drug: cisplatin; on the first day of treatment, patients were given 80mg/m2 cisplatin intravenously, and 21 days was a course of treatment, lasting for 6 courses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response (CR)	The tumor lesion in our patient completely resolved and lasted for ≥4 weeks, and no new lesion appeared	every 6 weeks
Partial response (PR)	the overall reduction in the longest diameter of the tumor focus is > 50% and it can be maintained for at least 4 weeks, with no new focus emerging	every 6 weeks
Stable disease (SD)	the overall reduction or increase of the longest diameter of the tumor lesion is < 50% or < 25%, and the duration is > 4 weeks; no new lesion appears	every 6 weeks
Disease progression (PD)	the combined increase in the longest diameter of the tumor lesion is ≥25%, or a new lesion appears	every 6 weeks

Collaborators and Investigators

• Sponsor: First People's Hospital of Hangzhou
• Collaborators: College of Pharmaceutical Sciences at Zhejiang University; The Innovation Institute for Artificial Intelligence in Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): June 30, 2026

Study Registration Dates

• First Submitted: December 12, 2022
• First Submitted That Met QC Criteria: December 26, 2022
• First Posted (Estimate): December 28, 2022

Study Record Updates

• Last Update Posted (Estimate): December 28, 2022
• Last Update Submitted That Met QC Criteria: December 26, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Alcohol Deterrents; Acetaldehyde Dehydrogenase Inhibitors; Cisplatin; Disulfiram
• Other Study ID Numbers: 20221212

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No