Ascorbic Acid and Combination Chemotherapy in Treating Patients With Locally Advanced or Recurrent Pancreatic Cancer That Cannot Be Removed by Surgery

Study Overview
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Brief Summary
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This pilot clinical trial studies the side effects of ascorbic acid and combination chemotherapy in treating patients with pancreatic cancer that has spread to other places in the body, has come back, or cannot be removed by surgery. Nutrients found in food and dietary supplements, such as ascorbic acid, may improve the tolerability of chemotherapy regimens. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ascorbic acid and combination chemotherapy may work better in treating patients with pancreatic cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine safety of intravenous ascorbic acid in combination with fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin (FOLFIRINOX) as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 in patients with advanced pancreatic cancer. SECONDARY OBJECTIVES: I. To test feasibility of collecting quality of life (QOL), patient reported outcomes (PRO) data and correlative studies on patients with advanced pancreatic cancer.

Official Title
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A Pilot Study of Intravenous Ascorbic Acid and Folfirinox in the Treatment of Advanced Pancreatic Cancer

Conditions
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Pancreatic Adenocarcinoma, Recurrent Pancreatic Carcinoma, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer, Unresectable Pancreatic Carcinoma

Intervention / Treatment
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* Drug: Oxaliplatin
* Drug: Irinotecan Hydrochloride
* Drug: Leucovorin Calcium
* Drug: Fluorouracil
* Dietary Supplement: Ascorbic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving informed consent Histological diagnosis of adenocarcinoma of the pancreas Stage IV or recurrent pancreatic cancer by imaging Locally advanced unresectable pancreatic cancer by National Comprehensive Cancer Network (NCCN) criteria Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 No prior treatment for metastatic disease (prior neo-adjuvant or adjuvant chemotherapy, except FOLFIRINOX, chemoradiation or radiation allowed) White blood count >= 3000 Platelets >= 100,000 Total bilirubin =< 1.5 mg/dl Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 5 X upper limit of normal (ULN) Creatinine < 1.5 mg/dL Glucose-6-phosphatase deficiency (G6PD) level of 5-14 units/g hemoglobin (Hgb) or within institutional standard parameters All subjects of child producing potential must agree to use contraception or avoidance of pregnancy measures while enrolled on study Exclusion Criteria: Other pancreatic cancer histology (islet cell, acinar, neuroendocrine tumors) Resectable pancreatic cancer Prior neoadjuvant FOLFIRINOX Pregnant or lactating females No clinical ascites (mild ascites on scans permissible) Central nervous system (CNS) metastasis Known congestive heart failure, significant ventricular arrhythmias, cirrhosis, grade 4/5 chronic kidney disease, uncontrolled diabetes Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy Peripheral neuropathy grade 2 or greater Any condition, psychiatric or otherwise, that would preclude informed consent, consistent follow-up or compliance with any aspect of the study (e.g., untreated schizophrenia or other significant cognitive impairment, etc.)

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (FOLFIRINOX, ascorbic acid)<br>Patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46 hours on day 1. Patients then receive ascorbic acid IV over 2 hours on days 3, 5, 8, 10 and 12. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. | Drug: Oxaliplatin<br>* Given IV<br>* Other names: trans-l diaminocyclohexane oxalatoplatinum;Drug: Irinotecan Hydrochloride<br>* Given IV<br>* Other names: Camptothecin 11;Drug: Leucovorin Calcium<br>* Given IV<br>* Other names: Wellcovorin;Drug: Fluorouracil<br>* Given IV<br>* Other names: Ro 2-9757;Dietary Supplement: Ascorbic Acid<br>* Given IV<br>* Other names: Vitamin C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events as Determined by CTCAE Version 4.03 | After 4 patients are enrolled on the study and receive at least one dose of intravenous ascorbic acid, the data will be reviewed. If 2 out of the 4 cannot complete 2 courses of FOLFIRINOX then the study will be halted. | Up to 28 days after the last treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of Life as Defined by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30 | Change in quality of life over the six measurement times will be modeled using mixed effects linear regression to account for correlation among repeated measurements from the same subjects. Average change in QoL from baseline to follow-up will be computed. | Baseline to up to 28 days after the last treatment |