Combination of IV Ascorbic Acid and Adebrelimab in Metastatic Colorectal Cancer

Phase 3

Recruiting

• Conditions: Colorectal Cancer; Vitamin C; GLUT3
• Interventions: Drug: Ascorbic acid; Drug: FOLFOX Protocol; Drug: Adebrelimab

• Registration Number: NCT04516681
• Lead Sponsor: Fudan University

Brief Summary

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 combination of therapeutic role of AA and PD-L1 antibody in metastatic colorectal cancer with high expression of GLUT3. This protocol is a randomized controlled study of AA infusions combined with Adebrelimab and FOLFOX +/- bevacizumab versus treatment with FOLFOX +/- bevacizumab alone in metastatic colorectal cancer patients with high expression of GLUT3.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-08-12
• Study First Submitted QC: 2020-08-14
• Study First Posted: 2020-08-18
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-22
• Last Update Posted: 2024-10-24
• Study Start: 2024-12-01
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 400

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combined Ascorbic Acid with Adebrelimab and chemotherapy group	Ascorbic acid	Ascorbic Acid with Adebrelimab and FOLFOX ± bevacizumab. Ascorbic Acid (1.5g/kg/day, D1-3) every 2 weeks
Combined Ascorbic Acid with Adebrelimab and chemotherapy group	FOLFOX Protocol	Ascorbic Acid with Adebrelimab and FOLFOX ± bevacizumab. Ascorbic Acid (1.5g/kg/day, D1-3) every 2 weeks
Combined Ascorbic Acid with Adebrelimab and chemotherapy group	Adebrelimab	Ascorbic Acid with Adebrelimab and FOLFOX ± bevacizumab. Ascorbic Acid (1.5g/kg/day, D1-3) every 2 weeks
Chemotherapy alone group	FOLFOX Protocol	standard FOLFOX treatment

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	up to 5 years	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

Secondary Outcome Measures

Name	Time	Method
Overall Survival	up to 5 years	Time to event outcome measure (death), measured in days from cycle 1 day 1
Progression Free Survival	up to 5 years	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

Trial Locations

Locations (1)

Fudan university shanghai cancer center; 🇨🇳 Shanhai, Shanghai, China