Combination of IV Ascorbic Acid and Adebrelimab in Metastatic Colorectal Cancer

NCT ID: NCT04516681

Last Updated: 2024-10-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2025-12-01

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.

Conditions

Colorectal Cancer; Vitamin C; GLUT3

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combined Ascorbic Acid with Adebrelimab and chemotherapy group

Ascorbic Acid with Adebrelimab and FOLFOX ± bevacizumab. Ascorbic Acid (1.5g/kg/day, D1-3) every 2 weeks

Group Type: EXPERIMENTAL

Ascorbic acid

Intervention Type: DRUG

1.5g/kg/day, D1-3, every 2 weeks

FOLFOX Protocol

Intervention Type: DRUG

Oxaliplatin 130 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

Adebrelimab

Intervention Type: DRUG

20mg/Kg intravenously every 3 weeks

Chemotherapy alone group

standard FOLFOX treatment

Group Type: ACTIVE_COMPARATOR

FOLFOX Protocol

Intervention Type: DRUG

Oxaliplatin 130 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

Interventions

Ascorbic acid

1.5g/kg/day, D1-3, every 2 weeks

Intervention Type: DRUG

FOLFOX Protocol

Oxaliplatin 130 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

Intervention Type: DRUG

Adebrelimab

20mg/Kg intravenously every 3 weeks

Intervention Type: DRUG

Other Intervention Names

Vitamin C; FOLFOX+/- bevacizumab

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Guoxiang Cai

Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Guoxiang Cai, Doctor

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan university shanghai cancer center

Shanhai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Guoxiang Cai

Role: CONTACT

gxcaifuscc@163.com

13122618708 ext. 13122618708

Renjie Wang

Role: CONTACT

wangbladejay@sina.com

18817519285 ext. +86

Facility Contacts

WEIXING DAI

Role: primary

wxdai17@fudan.edu.cn

13122618708 ext. 13122618708

Other Identifiers

Vitamin C-GLUT3-2020

Identifier Type: -

Identifier Source: org_study_id