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

Early Phase 1

Completed

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

Interventions: Drug: Oxaliplatin
Drug: Irinotecan Hydrochloride
Drug: Leucovorin Calcium
Drug: Fluorouracil
Dietary Supplement: Ascorbic Acid

Registration Number: NCT02896907

Lead Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 8

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.)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (FOLFIRINOX, ascorbic acid)	Leucovorin Calcium	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.
Treatment (FOLFIRINOX, ascorbic acid)	Ascorbic Acid	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.
Treatment (FOLFIRINOX, ascorbic acid)	Irinotecan Hydrochloride	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.
Treatment (FOLFIRINOX, ascorbic acid)	Oxaliplatin	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.
Treatment (FOLFIRINOX, ascorbic acid)	Fluorouracil	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events as Determined by CTCAE Version 4.03	Up to 28 days after the last treatment	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.

Secondary Outcome Measures

Name	Time	Method
Change in Quality of Life as Defined by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C-30	Baseline to up to 28 days after the last treatment	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.