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

Sidney Kimmel Cancer Center at Thomas Jefferson University

Status and phase: Completed; Early Phase 1

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

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02896907

16D.347

JT 8223 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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8 participants in 1 patient group

Treatment (FOLFIRINOX, ascorbic acid)

Experimental group

Description:

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:

Drug: Leucovorin Calcium

Dietary Supplement: Ascorbic Acid

Drug: Fluorouracil

Drug: Oxaliplatin

Drug: Irinotecan Hydrochloride