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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01515046
Recruitment Status : Terminated (Standard of care changed to FOLFIRINOX; poor accrual.)
First Posted : January 23, 2012
Results First Posted : March 29, 2017
Last Update Posted : June 8, 2017
Susan L Bader Foundation of Hope
Holden Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Joseph J. Cullen, University of Iowa

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.

Condition or disease Intervention/treatment Phase
Pancreatic Neoplasms Pancreatic Cancer Drug: Gemcitabine with escalating ascorbic acid Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacological Ascorbate for the Control of Metastatic and Node-Positive Pancreatic Cancer (PACMAN): A Phase II Trial
Study Start Date : September 2012
Actual Primary Completion Date : July 2015
Actual Study Completion Date : December 2016

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

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

Secondary Outcome Measures :
  1. 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.

  2. 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

  3. F2-isoprostane Levels [ Time Frame: Once every 28 days for up to 5 years ]
    F2-isoprostane is a marker of systemic oxidative stress.

  4. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01515046

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United States, Iowa
The Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242
Sponsors and Collaborators
Joseph J. Cullen
Susan L Bader Foundation of Hope
Holden Comprehensive Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Joseph J Cullen, MD University of Iowa
Study Chair: Joseph J Cullen, MD University of Iowa
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Responsible Party: Joseph J. Cullen, Professor of Surgery, University of Iowa Identifier: NCT01515046    
Other Study ID Numbers: 201204737
P30CA086862 ( U.S. NIH Grant/Contract )
First Posted: January 23, 2012    Key Record Dates
Results First Posted: March 29, 2017
Last Update Posted: June 8, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Joseph J. Cullen, University of Iowa:
Complementary medicine
Pancreatic cancer
Ascorbic Acid
Pharmacologic actions
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Ascorbic Acid
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protective Agents
Growth Substances