A Research Trial of High Dose Vitamin C and Chemotherapy for Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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This study is designed to determine the maximum tolerated dose of vitamin C when given with a standard chemotherapy for people who have metastatic pancreatic cancer.

Detailed Description
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This is a phase I, dose-escalating study of ascorbic acid (vitamin C) designed to determine the maximum tolerated dose of vitamin C or, if well tolerated, the dose required to obtain a desired ascorbic acid plasma concentration. Because this is a phase I study, prospective subjects should have advanced disease (i.e., metastasis) and have failed other curative therapies (or, are unable to receive curative therapies due to comorbidities or stage of disease).

Official Title
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A Phase I Trial of Ascorbic Acid and Gemcitabine for the Treatment of Metastatic Pancreatic Cancer

Conditions
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Pancreatic Neoplasms

Intervention / Treatment
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* Drug: Gemcitabine with escalating ascorbic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal G6PD status Histologically or cytologically diagnosed pancreatic adenocarcinoma. Disease extent documented by CT scan (radiologically measurable disease is not required) Ambulatory patient without evidence of spinal cord compression No prior chemotherapy for metastatic disease Failed curative therapy or patient ineligible for definitive curative therapy Completed adjuvant therapy at least 4 weeks prior and recovered from any/all toxicities related to that treatment. If post-therapy, must have disease progression since that treatment If treated with prior radiation therapy, disease must be outside of the radiation fields No currently active second malignancies unless it is a non-melanoma skin cancer Women must be non-pregnant and non-lactating ECOG performance of 0, 1, or 2 Granulocytes at least 1,500 / ul Platelets at least 100,000 / ul Creatinine less than 1.5 mg/dL or clearance of at least 60 mL / min Total bilirubin less than 2 times the upper limit of normal AST and ALT less than 3 times the upper limit of normal if liver metastases are not present. If liver metastases are present, AST and ALT less than 5 times the upper limit of normal PT INR less than 1.5 (unless the patient is on full dose warfarin) Patient must be at least 18 years of age Patient must be able to understand consent process, the research study, and be able to sign the consent document Exclusion Criteria: A psychiatric disorder by history or examination that would prevent completion of the study ECOG performance of 3 or 4 Co-morbid conditions that affect survival: end stage congestive heart failure, unstable angina, myocardial infarction (within the past 6 weeks), uncontrolled blood sugars of greater than 300 mg/dL, known chronic active hepatitis or cirrhosis. Consumption of excess alcohol (more than 4 drinks per day) or use of illicit drugs Continued sse of over-the-counter antioxidants (supplements like vitamin C and grape seeds)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ascorbate<br> | Drug: Gemcitabine with escalating ascorbic acid<br>* Gemcitabine (1000 mg/m2) weekly for three weeks and then one week off. Ascorbic acid, given twice weekly, escalating doses weekly. Week 1: 15 grams ascorbic acid per infusion Week 2: 25 grams ascorbic acid per infusion Week 3: 50 grams ascorbic acid per infusion Week 4: 75 grams ascorbic acid per infusion Week 5: 100 grams ascorbic acid per infusion Ascorbic acid infusion dose is maintained at the level that provides a serum level of 350-400 mg/dL.<br>* Other names: Ascor L 500;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood cell counts (neutropenia, thrombocytopenia) and serum chemistries (liver function tests, creatinine) |  | weekly | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma ascorbate level (targeted to 350 to 400 mg/dL) |  | Weekly | 
| Survival |  | Ongoing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ascorbic Acid, Gemcitabine