- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01515046
Clinical Trial of High-dose Vitamin C for Advanced Pancreatic Cancer (PACMAN-II)
Pharmacological Ascorbate for the Control of Metastatic and Node-Positive Pancreatic Cancer (PACMAN): A Phase II Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Iowa
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Iowa City, Iowa, United States, 52242
- The Holden Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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. |
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:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: up to 5 years
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Time to event outcome measure (death), measured in days from cycle 1 day 1.
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up to 5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression Free Survival
Time Frame: up to 5 years
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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.
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up to 5 years
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Number of Drug-related Adverse Events Per Cycle
Time Frame: every 28 days up to 5 years
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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
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every 28 days up to 5 years
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F2-isoprostane Levels
Time Frame: Once every 28 days for up to 5 years
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F2-isoprostane is a marker of systemic oxidative stress.
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Once every 28 days for up to 5 years
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Ascorbate Levels
Time Frame: Once every 28 days up to 5 years
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Ascorbate levels will be taken at the bottom of each cycle to assess therapeutic dose window.
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Once every 28 days up to 5 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Joseph J Cullen, MD, University of Iowa
- Study Chair: Joseph J Cullen, MD, University of Iowa
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Pancreatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Micronutrients
- Vitamins
- Antioxidants
- Gemcitabine
- Ascorbic Acid
Other Study ID Numbers
- 201204737
- P30CA086862 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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.
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