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

This study has been terminated.
(Standard of care changed to FOLFIRINOX; poor accrual.)
Sponsor:
Collaborators:
Susan L Bader Foundation of Hope
Holden Comprehensive Cancer Center
Information provided by (Responsible Party):
Joseph J. Cullen, University of Iowa
ClinicalTrials.gov Identifier:
NCT01515046
First received: January 18, 2012
Last updated: June 19, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Pancreatic Neoplasms
Pancreatic Cancer
Drug: Gemcitabine with escalating ascorbic acid
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacological Ascorbate for the Control of Metastatic and Node-Positive Pancreatic Cancer (PACMAN): A Phase II Trial

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • Overall survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    Time to event outcome measure (death), measured in days from cycle 1 day 1.


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    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

  • Number of drug-related adverse events per cycle [ Time Frame: every 28 days up to 5 years ] [ Designated as safety issue: Yes ]
    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

  • F2-isoprostane levels [ Time Frame: Once every 28 days for up to 5 years ] [ Designated as safety issue: Yes ]
    F2-isoprostane is a marker of systemic oxidative stress.

  • Ascorbate levels [ Time Frame: Once every 28 days up to 5 years ] [ Designated as safety issue: No ]
    Ascorbate levels will be taken at the bottom of each cycle to assess therapeutic dose window.


Enrollment: 1
Study Start Date: September 2012
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01515046

Locations
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
Investigators
Principal Investigator: Joseph J Cullen, MD The University of Iowa
Study Chair: Joseph J Cullen, MD The University of Iowa
  More Information

Publications:
Responsible Party: Joseph J. Cullen, Professor of Surgery, University of Iowa
ClinicalTrials.gov Identifier: NCT01515046     History of Changes
Other Study ID Numbers: PACMAN-II, P30CA086862
Study First Received: January 18, 2012
Last Updated: June 19, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Iowa:
Vitamins
Complementary medicine
Pancreatic cancer
Ascorbate
Ascorbic Acid
Antioxidants
Gemcitabine
Pharmacologic actions

Additional relevant MeSH terms:
Neoplasms
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Ascorbic Acid
Vitamins
Gemcitabine
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Micronutrients
Growth Substances
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 25, 2014