IV Ascorbic Acid in Peritoneal Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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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 therapeutic role of AA in peritoneal metastatic colorectal cancer with high expression of GLUT3. This protocol is a randomized controlled study of AA infusions combined with FOLFOXIRI +/- bevacizumab versus treatment with FOLFOXIRI +/- bevacizumab alone in peritoneal metastatic colorectal cancer patients with high expression of GLUT3.

Official Title
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Vitamin C Intravenously With Chemotherapy in Peritoneal Metastatic Colorectal Cancer With High Expresison Level of GLUT3

Conditions
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GLUT3, Colorectal Cancer, Vitamin C

Intervention / Treatment
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* Drug: Ascorbic acid
* Drug: FOLFOXIRI Protocol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined Ascorbic Acid with chemotherapy group<br>Ascorbic Acid with FOLFOXIRI with or without bevacizumab Ascorbic Acid (1.5g/kg/day, D1-3) every 2 weeks | Drug: Ascorbic acid<br>* 1.5g/kg/day, D1-3, every 2 weeks<br>* Other names: Vitamin C;Drug: FOLFOXIRI Protocol<br>* CPT-11 165 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<br>* Other names: FOLFOXIRI+/- bevacizumab;|
| Active Comparator: Chemotherapy alone group<br>standard FOLFOXIRI treatment | Drug: FOLFOXIRI Protocol<br>* CPT-11 165 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<br>* Other names: FOLFOXIRI+/- bevacizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | 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 | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | 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 | up to 5 years | 
| Overall Survival | Time to event outcome measure (death), measured in days from cycle 1 day 1 | up to 5 years |