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

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

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Adenocarcinoma; Unresectable Pancreatic Carcinoma; Recurrent Pancreatic Carcinoma; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer
• Intervention / Treatment: Drug: Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin Calcium; Drug: Irinotecan Hydrochloride; Dietary supplement: Ascorbic Acid

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center at Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (FOLFIRINOX, 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.

Drug: Fluorouracil; Given IV; Other Names: Fluracil; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; AccuSite; Fluracedyl; Fluroblastin; Ribofluor; Ro 2-9757; 19893; 2,4-Dioxo-5-fluoropyrimidine; Drug: Oxaliplatin; Given IV; Other Names: Dacotin; Dacplat; Eloxatin; Ai Heng; Diaminocyclohexane Oxalatoplatinum; Oxalatoplatin; 61825-94-3; trans-l diaminocyclohexane oxalatoplatinum; [(1R,-2R)-1,2-cyclohexanediamine-N,N'][oxalato (2--)-O,O']platinum; [Sp-4-2-(1R-trans)]-(1,2,cyclohexanediamine-N,N')[ethanedioato(2--)-O,O']platinum; Drug: Leucovorin Calcium; Given IV; Other Names: Wellcovorin; Adinepar; Calcifolin; Calcium (6S)-Folinate; Calcium Folinate; Calfolex; Calinat; Cehafolin; Citofolin; Citrec; Citrovorum Factor; Cromatonbic Folinico; Dalisol; Disintox; Divical; Ecofol; Emovis; Flynoken A; Folaren; Folaxin; Foliben; Folinic Acid Calcium Salt Pentahydrate; Folix; Lederfolin; Leucosar; Rescufolin; Rescuvolin; Tonofolin; 1492-18-8; 5-Formyl Tetrahydrofolate; 5-Formyl-5,6,7,8-tetrahydrofolic Acid; 5-Formyl-5,6,7,8-tetrahydropteroyl-L-glutamic Acid; 3590; Calcium N-(p-((((6RS)-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl)methyl)amino)benzoyl)-L-glutamate (1:1); N-[4-[[(2-Amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl]amnio]benzoyl]-L-glutamic Acid; Drug: Irinotecan Hydrochloride; Given IV; Other Names: Campto; Camptosar; Camptothecin 11; 136572-09-3; Dietary supplement: Ascorbic Acid; Given IV; Other Names: Vitamin C; 2-(1,2-dihydroxyethyl)-4,5-dihydroxy-furan-3-one; Asorbicap; C Vitamin; C-Long; Ce-Vi-Sol; Cecon; Cenolate; L-Ascorbic Acid; 33832; 50-81-7

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Investigators: Principal Investigator: James Posey, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Publications and helpful links

Helpful Links

• Thomas Jefferson University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2016
• Primary Completion (Actual): March 22, 2018
• Study Completion (Actual): March 1, 2019

Study Registration Dates

• First Submitted: September 6, 2016
• First Submitted That Met QC Criteria: September 6, 2016
• First Posted (Estimated): September 12, 2016

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 28, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Pancreatic Neoplasms; Calcium-Regulating Hormones and Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Bone Density Conservation Agents; Micronutrients; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Antioxidants; Protective Agents; Antidotes; Vitamin B Complex; Oxaliplatin; Irinotecan; Calcium, Dietary; Calcium; Fluorouracil; Leucovorin; Levoleucovorin; Camptothecin; Ascorbic Acid; Vitamins; Tetrahydrofolates; Formyltetrahydrofolates
• Other Study ID Numbers: 16D.347; JT 8223 (Other Identifier: JeffTrial Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes