Clinical Trial of High-dose Vitamin C for Advanced Pancreatic Cancer

NCT01515046 | Terminated Phase 2 Results DMC

• 2 other identifiers: 201204737P30CA086862
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II study. It is designed to provide information about if high-dose ascorbate (vitamin C) increases survival for pancreatic cancer patients. The hypothesis is that vitamin C is well tolerated and increases cancer treatment effectiveness, lengthening survival time for patients with advanced pancreatic cancer.

Conditions

Pancreatic Neoplasms; Pancreatic Cancer

Keywords

Vitamins; Complementary medicine; Pancreatic cancer; Ascorbate; Ascorbic Acid; Antioxidants; Gemcitabine; Pharmacologic actions

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Time to event outcome measure (death), measured in days from cycle 1 day 1.

  up to 5 years

Secondary Outcomes (4)

• Progression Free Survival

  up to 5 years

• Number of Drug-related Adverse Events Per Cycle

  every 28 days up to 5 years

• F2-isoprostane Levels

  Once every 28 days for up to 5 years

• Ascorbate Levels

  Once every 28 days up to 5 years

Study Arms (1)

Gemcitabine with escalating IV ascorbate

EXPERIMENTAL

Gemcitabine (1000 mg/m2) weekly for three weeks and then one week off. Ascorbic Gemcitabine (1000 mg/m2) weekly for three weeks and then one week off. Ascorbate (vitamin C) given twice weekly, escalating doses weekly. Week 1: 15 grams ascorbate / infusion for two infusions. Doses are then escalated in 25 gram increments until therapeutic window is achieved (350 mg/dL or above). Dose is then held at that level for the full cycle.

Drug: Gemcitabine with escalating ascorbic acid

Interventions

Gemcitabine with escalating ascorbic acid DRUG

Gemcitabine 1000 mg/m2 weekly for 3 weeks with one week off (this is 1 cycle) Ascorbate dose is targeted to achieve plasma level of 350 mg/dL. Infusions are given twice weekly, each week of a cycle (4 weeks to a cycle)

Also known as: Gemzar, Ascorbic Acid for Infusion, USP

Gemcitabine with escalating IV ascorbate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a cytological or histological diagnosis of adenocarcinoma arising in the pancreas. Diagnosis from metastatic sampling is acceptable.
• Disease must be measured radiologically.
• Failed initial therapy or ineligible for definitive curative therapy.
• If prior treatment included radiation therapy, recurrent disease must be outside of the targeted volume.
• Age ≥ 18 years
• ECOG performance status 0-2 (Karnofsky \> 50%, see Appendix A).
• Patients must have normal organ and marrow function as defined below:
• leukocytes ≥ 3,000/mm3
• absolute neutrophil count ≥ 1,500/mm3
• platelets ≥ 100,000/mm3
• total bilirubin \< 2x institutional upper limit of normal
• AST(SGOT) \< 3x institutional upper limit of normal OR \< 5x institutional upper limit of normal for patients presenting with liver metastases
• ALT (SGPT) \< 3x institutional upper limit of normal OR \< 5x institutional upper limit of normal for patients presenting with liver metastases
• PT/INR within normal institutional limits, unless patient is on warfarin or other antithrombotic agents
• creatinine \< 1.5 X institutional upper limit of normal OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

You may not qualify if:

• Prior chemotherapy to treat metastatic disease.
• Adjuvant therapy (including radiation therapy) within 4 calendar weeks.
• Unresolved toxicities from prior therapy for the malignancy.
• G6PD (glucose-6-phosphate dehydrogenase) deficiency.
• Second malignancy other than non-melanoma skin cancers within the past 5 years.
• Excess consumption of alcohol where an excess of alcohol is defined as more than four of any one of the following per day: 30 mL distilled spirits, 340 mL beer, or 120 mL wine.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness/social situations, or any other condition that would limit compliance with study requirements as determined by study team members.
• Pregnant or lactating women: The risks of chemotherapy to a fetus/infant are well documented.

Sponsors & Collaborators

• Joseph J. Cullen: lead
• Susan L Bader Foundation of Hope: collaborator
• Holden Comprehensive Cancer Center: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

The Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Related Publications (3)

• Cullen JJ. Ascorbate induces autophagy in pancreatic cancer. Autophagy. 2010 Apr;6(3):421-2. doi: 10.4161/auto.6.3.11527. Epub 2010 Apr 15.

  PMID: 20400857 BACKGROUND

• Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang SH, Taghiyev AF, Du C, Knudson CM, Cullen JJ. Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer. Clin Cancer Res. 2010 Jan 15;16(2):509-20. doi: 10.1158/1078-0432.CCR-09-1713. Epub 2010 Jan 12.

  PMID: 20068072 BACKGROUND

• Welsh JL, Wagner BA, van't Erve TJ, Zehr PS, Berg DJ, Halfdanarson TR, Yee NS, Bodeker KL, Du J, Roberts LJ 2nd, Drisko J, Levine M, Buettner GR, Cullen JJ. Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial. Cancer Chemother Pharmacol. 2013 Mar;71(3):765-75. doi: 10.1007/s00280-013-2070-8. Epub 2013 Feb 5.

  PMID: 23381814 BACKGROUND

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; Ascorbic Acid

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Limitations and Caveats

There was only one treated participant. Conclusions cannot be drawn from these data due to limited sampling size.

Results Point of Contact

• Title: Joseph J. Cullen, MD, FACS
• Organization: The University of Iowa

joseph-cullen@uiowa.edu

319-353-8297

Study Officials

• Joseph J Cullen, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

• Joseph J Cullen, MD

  University of Iowa

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Surgery

Study Record Dates

• First Submitted: January 18, 2012
• First Posted: January 23, 2012
• Study Start: September 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: December 1, 2016
• Last Updated: June 8, 2017
• Results First Posted: March 29, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)