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

Study Overview
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Brief Summary
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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.

Detailed Description
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Phase I: To assess whether or not (IV) Ascorbic Acid (AA) with irinotecan therapy is relatively safe and well-tolerated. This aim will be assessed by enrolling a minimum of 6 subjects meeting inclusion criteria, using a modified 3+3 design. Safety will be assessed with the following: toxicity graded by the NCI CTC, urinalysis pre- and post-infusion, basic metabolic panel, and CBC. From our experience and in the experience of our study collaborators, we hypothesize that the combination of IV AA with irinotecan will not be associated with adverse events. Phase II: To utilize CT or PET/CT (when available) scans to evaluate disease progression to assess overall tumor response rate (complete and partial response) in subjects with advanced or recurrent colorectal cancer treated with the combination of ascorbic acid and irinotecan versus irinotecan alone.

Official Title
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Phase I/II Study of Intravenous Ascorbic Acid in Combination With Irinotecan Versus Irinotecan Alone for Advanced Colorectal Cancer

Conditions
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Stage IV Colorectal Cancer

Intervention / Treatment
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* Drug: Ascorbic Acid
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 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: Ascorbic Acid + Irinotecan<br>Ascorbic Acid (50-100g, 3x weekly) with 350mg/m2 irinotecan once a week every 3 weeks | Drug: Ascorbic Acid<br>* 3x a week for 9 weeks<br>* Other names: Vitamin C;Drug: Irinotecan<br>* 350mg/m2 once a week every 3 weeks<br>* Other names: CPT-11;|
| Active Comparator: Standard of Care (irinotecan alone)<br>350mg/m2 irinotecan once a week every 3 weeks | Drug: Irinotecan<br>* 350mg/m2 once a week every 3 weeks<br>* Other names: CPT-11;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Experience Serious Adverse Events as Defined by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. | Safety: 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. | 9 weeks +/- 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Are Alive After 11 Weeks. | To evaluate progression-free survival related to treatment of patients with advanced or recurrent colorectal cancer | 9 weeks +/- 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoplasms by Site, Stage IV Colorectal cancer, Colorectal Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms, Digestive System Diseases, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases, Ascorbic Acid, Vitamins, Irinotecan, Integrative Medicine, Complementary Medicine, Alternative Medicine Antioxidants, Molecular Mechanisms of Pharmacological Action, Pharmacologic Actions, Protective Agents, Physiological Effects of Drugs, Micronutrients, Growth Substances, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Therapeutic Uses, Radiation-Sensitizing Agents, Topoisomerase I Inhibitors, Topoisomerase Inhibitors, Enzyme Inhibitors