Research Study of IV Vitamin C in Combination With Irinotecan vs Irinotecan Alone for Advanced Colorectal CA

• Safety [ Time Frame: 9 weeks +/- 2 weeks ] [ Designated as safety issue: Yes ]
  the primary aim is to assess whether or not (IV) Ascorbic Acid (AA) with irinotecan therapy is relatively safe and well-tolerated according to Common Terminology Criteria for Adverse Events (CTCAE)v4.0
• Efficacy [ Time Frame: 9 weeks +/- 2 weeks ] [ Designated as safety issue: No ]
  To utilize CT or PET/CT scans to assess overall tumor response rate (complete and partial response) and evaluate disease progression in subjects with advanced or recurrent colorectal cancer treated with the combination of ascorbic acid and irinotecan versus irinotecan alone.

This protocol is a phase I/II, study of ascorbic acid (AA) infusions combined with treatment with irinotecan versus treatment with irinotecan alone in patients with recurrent or advanced colorectal cancer who have failed at least one treatment regimen with a 5-FU based therapy. This study will be conducted as an amendment to Investigational New Drug # 77486.

Inclusion Criteria:

• Age > 18 years
• Metastatic colorectal carcinoma (stage IV disease).
• Patients must have progressed on one or more prior chemotherapy treatment regimens including at least one trial of a 5-FU/oxaliplatin based therapy (FOLFOX) in combination with bevacizumab. Patients must not have had standard chemotherapy within at least 2 weeks of beginning ascorbic acid treatment provided that they have recovered from any toxicities that they experienced.
• G6PD status > lower limit of normal
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• 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); transaminase (AST/ALT) ≤2.0X upper limit of normal; bilirubin levels ≥ 2 mg/dL; ANC ≥1,500/mm3; Hemoglobin > 8g/dL; platelet ≥ 100,000/mm3;
• Women of childbearing potential will confirm a negative pregnancy test and must practice effective contraception during the study.
• Willing and able to provide informed consent and participate in the study procedures.

Exclusion Criteria:

• Patients with evidence of a significant current psychiatric disorder that would prevent completion of the study as determined by the PI will not be allowed to participate.
• Co-morbid medical condition that would affect survival or tolerance as determined by the PI. This includes patients who have not fully recovered from toxicities associated with prior therapy. It also includes subjects who, as determined by the PI, are at risk of experiencing fluid overload (i.e., congestive heart failure).
• Patients who currently abuse alcohol or drugs.
• Patients with known glomerular filtration rate of <60ml/min or with nephrotic range proteinuria.
• Pregnant or lactating women
• Enrollment in active clinical trial/ experimental therapy or IND study within the prior 30 days.
• Contraindication for CT or PET/CT as per the PI.
• Patients who are on strong inducers of CYP3A4 which include but are not limited to: Aminoglutethimide, Bexarotene, Bosentan, Carbamazepine, Dexamethasone, Efavirenz, Fosphenytoin, Griseofulvin, Modafinil, Nafcillin, Nevirapine, Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, Rifapentine, St. John's wort.