Colorectal Cancer, Vitamin C, GLUT3
Conditions
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.
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
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Overall Survival | up to 5 years | Time to event outcome measure (death), measured in days from cycle 1 day 1 |
Countries
China
Contacts
Primary ContactGuoxiang Cai
Backup ContactRenjie Wang
Outcome results
None listed