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Pancreatic NeoplasmsPhase 2PACMAN-IINCT01515046

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

A Phase 2 study testing Gemcitabine with escalating ascorbic acid in people with Pancreatic Neoplasms and Pancreatic Cancer, run by Joseph J. Cullen at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreatic Neoplasms, Pancreatic Cancer
What is being tested?
Gemcitabine with escalating ascorbic acid
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
Sep 2012to Dec 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
Show all 17Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Gemcitabine with escalating ascorbic acid
Keywords
Vitamins, Complementary medicine, Pancreatic cancer, Ascorbate, Ascorbic Acid, Antioxidants, Gemcitabine, Pharmacologic actions
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gemcitabine with escalating ascorbic acidDrug

    Also called Gemzar, Ascorbic Acid for Infusion, USP

    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)

Study groups in NCT01515046
Study groupRoleWhat they receive
Gemcitabine with escalating IV ascorbateExperimentalGemcitabine (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.
Receives: Drug: Gemcitabine with escalating ascorbic acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    Time to event outcome measure (death), measured in days from cycle 1 day 1.

    Measured: up to 5 years

Secondary outcomes (4)

  1. Progression Free Survival

    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.

    Measured: up to 5 years

  2. Number of Drug-related Adverse Events Per Cycle

    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

    Measured: every 28 days up to 5 years

  3. F2-isoprostane Levels

    F2-isoprostane is a marker of systemic oxidative stress.

    Measured: Once every 28 days for up to 5 years

  4. Ascorbate Levels

    Ascorbate levels will be taken at the bottom of each cycle to assess therapeutic dose window.

    Measured: Once every 28 days up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionJul 2015
  4. Study completionDec 2016

Why it stopped: Standard of care changed to FOLFIRINOX; poor accrual.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01515046
Sponsor's protocol ID
201204737
Other IDs
P30CA086862
Acronym
PACMAN-II
Status last verified
May 2017
First submitted
18 Jan 2012
Last updated
8 Jun 2017
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 20400857

  • 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.

    PubMed 20068072

  • 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.

    PubMed 23381814

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Gemcitabine with escalating ascorbic acid in people with Pancreatic Neoplasms and Pancreatic Cancer, run by Joseph J. Cullen at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01515046, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2017.

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