IV Ascorbic Acid in Peritoneal Metastatic Colorectal Cancer

Vitamin C Intravenously With Chemotherapy in Peritoneal Metastatic Colorectal Cancer With High Expresison Level of GLUT3

Previous preclinical study has shown that high levels of ascorbic acid (AA) possesses the ability to kill human colorectal cancer cells and high expression of GLUT3 will augment the efficacy of AA. To date, no previous studies have investigated the therapeutic role of AA in peritoneal metastatic colorectal cancer with high expression of GLUT3. This protocol is a randomized controlled study of AA infusions combined with FOLFOXIRI +/- bevacizumab versus treatment with FOLFOXIRI +/- bevacizumab alone in peritoneal metastatic colorectal cancer patients with high expression of GLUT3.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Vitamin C; GLUT3
• Intervention / Treatment: Drug: Ascorbic acid; Drug: FOLFOXIRI Protocol

• Study Type: Interventional
• Enrollment (Anticipated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Guoxiang Cai; Phone Number: 13122618708 13122618708; Email: gxcaifuscc@163.com
• Study Contact Backup: Name: Renjie Wang; Phone Number: +86 18817519285; Email: wangbladejay@sina.com

Study Locations

• China
  • Shanghai
    • Shanhai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: WEIXING DAI; Phone Number: 13122618708 13122618708; Email: wxdai17@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age≥18 years, ≤75 years; Histologically proven peritoneal metastatic adenocarcinoma of colorectal cancer, unresectable metastatic disease; IHC confirmed strong positive GLUT3; measurable disease; Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1; Life expectancy of at least 12 weeks; ANC ≥1,500/mm3; Hemoglobin > 8g/dL; platelet ≥ 100,000/mm3; Laboratory at baseline evaluation for inclusion in the study: creatinine ≤1.5X upper limit [if the creatinine is elevated, but ≤1.5X the ULN, a 24 hour creatinine clearance will be obtained, Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault)]; Transaminase (AST/ALT) ≤2.5X upper limit of normal and bilirubin levels ≤1.5X upper limit of normal without liver metastasis; Transaminase (AST/ALT) ≤5X upper limit of normal and bilirubin levels ≤1.5X upper limit of normal with liver metastasis; Written informed consent

Exclusion Criteria:

• Prior treatment for metastatic disease (adjuvant therapy with fluoropyrimidines +/-oxaliplatin based regimens allowed if stopped 12 months prior to registration on study); Surgery (excluding diagnostic biopsy) or irradiation within 3 weeks prior to study entry; Administration of any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment; Concurrent chronic systemic immune therapy, chemotherapy, radiation therapy (palliative radiation therapy allowed) or hormone therapy not indicated in the study protocol; Brain metastasis (known or suspected); Pregnant or lactating women; Other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection; Known allergy or any other adverse reaction to any of the drugs or to any related compound; Previous (within 5 years) or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and basal cell carcinoma of the skin; Patients with low or moderate expression of GLUT3.

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
EXPERIMENTAL: Combined Ascorbic Acid with chemotherapy group; Ascorbic Acid with FOLFOXIRI with or without bevacizumab Ascorbic Acid (1.5g/kg/day, D1-3) every 2 weeks	Drug: Ascorbic acid; 1.5g/kg/day, D1-3, every 2 weeks; Other Names: Vitamin C; Drug: FOLFOXIRI Protocol; CPT-11 165 mg/m² d1 concurrent with Leucovorin 400 mg/m², followed by Oxaliplatin 85 mg/m² d1 followed by Bolus 5FU 400 mg/m² , followed by Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks with or without bevacizumab 5mg/kg, every 2 weeks; Other Names: FOLFOXIRI+/- bevacizumab
ACTIVE_COMPARATOR: Chemotherapy alone group; standard FOLFOXIRI treatment	Drug: FOLFOXIRI Protocol; CPT-11 165 mg/m² d1 concurrent with Leucovorin 400 mg/m², followed by Oxaliplatin 85 mg/m² d1 followed by Bolus 5FU 400 mg/m² , followed by Infusional 5FU 2400 mg/m² over 46 hours, every 2 weeks with or without bevacizumab 5mg/kg, every 2 weeks; Other Names: FOLFOXIRI+/- bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	To utilize CT or MRI scans to assess overall tumor response rate (complete and partial response) in subjects with peritoneal metastatic colorectal cancer treated with the combination of ascorbic acid and FOLFOXIRI +/- bevacizumab versus treatment with FOLFOXIRI +/- bevacizumab alone	up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Time-to-event outcome measure (initial disease progression) measured in days from cycle 1 day 1 to day of first progression as defined by RECIST1.1 criteria from NCI	up to 5 years
Overall Survival	Time to event outcome measure (death), measured in days from cycle 1 day 1	up to 5 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Guoxiang Cai, Doctor, Fudan University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2020
• Primary Completion (ANTICIPATED): September 1, 2022
• Study Completion (ANTICIPATED): September 1, 2023

Study Registration Dates

• First Submitted: August 12, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (ACTUAL): August 18, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 14, 2020
• Last Verified: August 1, 2020

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; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: Vitamin C-GLUT3-2020

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