Repurposing the Antipsychotic Drug Chlorpromazine as Adjuvant Therapeutic Agent for Resected Stage III Colon Cancer

Repurposing the Antipsychotic Drug Chlorpromazine as Adjuvant Therapeutic Agent for Resected Stage III Colon Cancer: A Pilot, Randomized, Open Label, Controlled Study.

chlorpromazine displays a series of remarkable bio-molecular effects in cancer cells, as inhibition of cell growth, nuclear aberrations, inhibition of the phosphoinositide 3-kinase/mammilian target of rapamycin (PI3K/mTOR) axis, induction of cytotoxic autophagy, inhibition of glutamate and DRD2 receptors. This study will evaluate the addition of chlorpromazine to the first-line therapeutic protocol in colon cancer stage III.

Study Overview

• Status: Withdrawn
• Conditions: Colon Cancer Stage III
• Intervention / Treatment: Drug: Control; Drug: ChlorproMAZINE 50 MG

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Menoufia
    • Sadat City, Menoufia, Egypt, 13829
      • Faculty of Pharmacy, University of Sadat city

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients age ≥18 years old.
• Patients with histologically confirmed surgically resected stage III colon cancer
• No rectal cancer
• Stage III disease (any pT, N1-2, M0)
• Patients should have a good performance status according to Eastern Cooperative Oncology Group (ECOG) score (ECOG 0-2).

• Patients with normal organic function as defined for the following criteria:

  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 times the upper normal limit of the local laboratory (LSN-LL);
  • Total serum bilirubin ≤ 2.0 x ULN-LL;
  • Absolute neutrophil count ≥ 1,500 / mm3;
  • Platelet count ≥ 100,000 / mm3;
  • Hemoglobin ≥ 8.0 g / dl;
  • Serum creatinine ≤ 1.5 x ULN-LL
• Patients should undergone curative-intent complete surgical resection
• Patients have at least one month from any major surgery to start of intervention
• Written informed consent before enrollment

Exclusion Criteria:

• Patients with concurrent other malignancy or history of other malignancy treated within the past 3 years (other than non-melanoma skin cancer or in-situ cervical cancer)
• Patients with metastatic disease
• Patients who scheduled to receive any form of further adjuvant cancer therapy (A malignancy currently under active therapy
• Pregnant or breast-feeding patients
• Patients with known hypersensitivity or intolerance to CPZ
• Patients with serious illness or psychiatric condition.
• Patients have current participation in other protocols with experimental drugs.
• Patients with no ability to ingest food orally.
• Patients who have familial adenomatous polyposis, hereditary non-polyposis rectal cancer, or inflammatory bowel disease
• Patients who are taken other chemoprevention drugs (ex. NSAIDs, Aspirin)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Control	Drug: Control; The control group will receive folinic acid, fluorouracil and oxaliplatin (mFOLFOX6) regimen every 14 days for (6-12 cycles) (6 months) (Day 1: 5-FU IV 400 mg/m2, leucovorin IV 400 mg/m2, oxaliplatin IV 85 mg/m2, 5-FU continuous IV infusion (CIVI) 1200 mg/m2/day x 2 days (over 46-48 hours)
EXPERIMENTAL: Chloropromazine	Drug: ChlorproMAZINE 50 MG; The experimentall group will receive folinic acid, fluorouracil and oxaliplatin (mFOLFOX6) regimen every 14 days for (6-12 cycles) (6 months) (Day 1: 5-FU IV 400 mg/m2, leucovorin IV 400 mg/m2, oxaliplatin IV 85 mg/m2, 5-FU continuous IV infusion (CIVI) 1200 mg/m2/day x 2 days (over 46-48 hours) plus choloropromazine 50 mg daily for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Disease-free survival as measured by Logrank	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival as measured by Logrank	one year
Time occurrence of new primary colon cancer and new polyps	Time occurrence of new primary colon cancer and new polyps as measured by Logrank	one year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biological Markers	Blood and serum level of apoptotic and inflammatory markers (Sirtuin 1 (SIRT1) - p53 - TNF-α - Caspase 3)	6 months

Collaborators and Investigators

• Sponsor: Sadat City University

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 20, 2022
• Primary Completion (ACTUAL): September 30, 2022
• Study Completion (ACTUAL): September 30, 2022

Study Registration Dates

• First Submitted: June 22, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (ACTUAL): June 27, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 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; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Chlorpromazine
• Other Study ID Numbers: Onco-2022-7

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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