Combination of IV Ascorbic Acid and Adebrelimab in Metastatic Colorectal Cancer

Fudan University

Status and phase: Enrolling; Phase 3

Conditions: GLUT3; Vitamin C; Colorectal Cancer

Treatments: Drug: Ascorbic acid; Drug: FOLFOX Protocol; Drug: Adebrelimab

Study type: Interventional

Funder types: Other

Identifiers

NCT04516681

Vitamin C-GLUT3-2020

Details and patient eligibility

About

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.

Enrollment: 400 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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400 participants in 2 patient groups

Combined Ascorbic Acid with Adebrelimab and chemotherapy group

Experimental group

Description:

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

Treatment:

Drug: Adebrelimab

Drug: FOLFOX Protocol

Drug: Ascorbic acid

Chemotherapy alone group

Active Comparator group

Description:

standard FOLFOX treatment

Treatment:

Drug: FOLFOX Protocol