Clinical Trial of High-dose Vitamin C for Advanced Pancreatic Cancer
Information source: University of Iowa
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pancreatic Neoplasms; Pancreatic Cancer
Intervention: Gemcitabine with escalating ascorbic acid (Drug)
Phase: Phase 2
Status: Terminated
Sponsored by: Joseph J. Cullen Official(s) and/or principal investigator(s): Joseph J Cullen, MD, Principal Investigator, Affiliation: The University of Iowa Joseph J Cullen, MD, Study Chair, Affiliation: The University of Iowa
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.
Clinical Details
Official title: Pharmacological Ascorbate for the Control of Metastatic and Node-Positive Pancreatic Cancer (PACMAN): A Phase II Trial
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Overall survival
Secondary outcome: Progression Free SurvivalNumber of drug-related adverse events per cycle F2-isoprostane levels Ascorbate levels
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
The Holden Comprehensive Cancer Center, Iowa City, Iowa 52242, United States
Additional Information
Related publications: Cullen JJ. Ascorbate induces autophagy in pancreatic cancer. Autophagy. 2010 Apr;6(3):421-2. Epub 2010 Apr 15. 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. 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.
Starting date: September 2012
Last updated: May 26, 2015
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