RecruitingPhase 3NCT04516681

Combination of IV Ascorbic Acid and Adebrelimab in Metastatic Colorectal Cancer

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


Sponsor

Fudan University

Enrollment

400 participants

Start Date

Dec 1, 2024

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 75 Years

Inclusion Criteria1

  • 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 Criteria1

  • 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.

Interventions

DRUGAscorbic acid

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

DRUGFOLFOX 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

DRUGAdebrelimab

20mg/Kg intravenously every 3 weeks


Locations(1)

Fudan university shanghai cancer center

Shanhai, Shanghai Municipality, China

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NCT04516681


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