Clinical Trial of High-dose Vitamin C for Advanced Pancreatic Cancer (PACMAN-II)

May 11, 2017 updated by: Joseph J. Cullen

Pharmacological Ascorbate for the Control of Metastatic and Node-Positive Pancreatic Cancer (PACMAN): A Phase II Trial

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Adenocarcinoma of the pancreas is the fourth leading cause of cancer death in the United States and is increasing in incidence; the prognosis remains dismal. We propose to investigate an entirely new approach, using pharmacological ascorbate, combined with Gemcitabine, to treat this cancer. Intravenous ascorbate (i.e., ascorbic acid, vitamin C), but not oral ascorbate, produces high plasma concentrations, which are in the range that can be cytotoxic to tumor cells. Though ascorbate has been utilized in cancer therapy, few studies have investigated intravenous deliver of ascorbate. Preliminary studies from our group have demonstrated that ascorbate induces oxidative stress and cytotoxicity in pancreatic cancer cells; this cytotoxicity appears to be greater in tumor vs. normal cells. We hypothesize that production of H2O2 mediates the increased susceptibility of pancreatic cancer cells to ascorbate-induced metabolic oxidative stress. Gemcitabine is the standard chemotherapy drug used to treat pancreatic cancer.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • The Holden Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.
    • Not pregnant. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
    • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Gemcitabine with escalating IV ascorbate

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

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)

Other Names:
  • Gemzar
  • Ascorbic Acid for Infusion, USP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: up to 5 years
Time to event outcome measure (death), measured in days from cycle 1 day 1.
up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: up to 5 years
Time-to-event outcome measure (initial disease progression) measured in days from cycle 1 day 1 to day of first progression as defined by RECIST criteria from NCI.
up to 5 years
Number of Drug-related Adverse Events Per Cycle
Time Frame: every 28 days up to 5 years
Adverse events linked to ascorbate will be categorized and quantified using CTCAE v4 at the bottom of each cycle. Incidence and frequency will be compared to scientific literature
every 28 days up to 5 years
F2-isoprostane Levels
Time Frame: Once every 28 days for up to 5 years
F2-isoprostane is a marker of systemic oxidative stress.
Once every 28 days for up to 5 years
Ascorbate Levels
Time Frame: Once every 28 days up to 5 years
Ascorbate levels will be taken at the bottom of each cycle to assess therapeutic dose window.
Once every 28 days up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Joseph J. Cullen

Collaborators

National Cancer Institute (NCI)
Holden Comprehensive Cancer Center
Susan L Bader Foundation of Hope

Investigators

  • Principal Investigator: Joseph J Cullen, MD, University of Iowa
  • Study Chair: Joseph J Cullen, MD, University of Iowa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

January 18, 2012

First Submitted That Met QC Criteria

January 18, 2012

First Posted (Estimate)

January 23, 2012

Study Record Updates

Last Update Posted (Actual)

June 8, 2017

Last Update Submitted That Met QC Criteria

May 11, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201204737
  • P30CA086862 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe