A Phase 2 Trial of High-dose Ascorbate for Pancreatic Cancer (PACMAN 2.1)

October 18, 2023 updated by: Joseph J. Cullen

A Phase II Trial of Pharmacological Ascorbate, Gemcitabine, and Nab-Paclitaxel for Metastatic Pancreatic Cancer (PACMAN 2.1)

This clinical trial adds high-dose ascorbate (vitamin C) to the standard of care regimen for metastatic pancreatic adenocarcinoma (a type of pancreatic cancer). Subjects are randomized between a control group (standard treatment) and an intervention group (pharmacologic ascorbate in addition to the standard treatment).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

One of the standard treatments for metastatic pancreatic adenocarcinoma is nab-paclitaxel with gemcitabine. This standard therapy administers chemotherapy once per week for three weeks; patients then get a 'rest week' to complete the cycle (1 cycle = 4 weeks).

This study adds 75 grams of ascorbate (vitamin C, sometimes called pharamcological ascorbate because the dose is so high) to standard therapy. The ascorbate is administered intravenously - through a vein in the arm.

Participants in the control group will:

  • receive gemcitabine and nab-paclitaxel chemotherapy, which is standard for their cancer.
  • undergo imaging which is standard for their cancer and therapy. This can include CT scans, PET scans, and X-rays

Participants in the intervention group will:

  • receive 75 grams of ascorbate 3 times per calendar week for each week of the chemotherapy cycle.
  • undergo imaging which is standard for their cancer and therapy. This can include CT scans, PET scans, and X-rays
  • provide blood samples to determine the biological effects, if any, the ascorbate has on the body during therapy.

This active therapy portion lasts until the disease progresses and a new treatment needs to be adopted - this can be months to years. If disease progresses, participants go back to standard follow-up for their caner and the new/additional therapy their doctors prescribe.

However, it is very important we remain in contact with participants; they will have life-long follow-up for this study.

Study Type

Interventional

Enrollment (Estimated)

65

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Holden Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologic diagnosis (cell samples, biopsy, brushing, surgical sample) of adenocarcinoma of the pancreas. Cancer from the Ampullae of Vater is also eligible. The tissue sample can be from a metastatic location, like a lymph node.
  • Metastatic or node positive disease
  • One cancer site, that did not receive radiation therapy, that is at least 1 cm in size when looking at it by CT scan (CAT scan)
  • Recommended to receive gemcitabine and nab-paclitaxel
  • Failed initial therapy or be ineligible for definitive curative therapy (e.g., surgical excision, radiation therapy)
  • A platelet count of at least 100,000 cells per mL
  • A creatinine level of less than 1 1/2 times the upper limit of normal for the local lab test, or, a creatinine clearance of at least 60 mL/(min*1.73m2)
  • Not pregnant
  • Commit to using birth control during the study (all participants)

Exclusion Criteria:

  • Prior chemotherapy to treat the metastatic disease
  • Other therapy (including radiation) within the past 4 weeks
  • Side effects from prior therapies that are still deemed moderate to severe by a physician
  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Patients actively receiving insulin or who are currently recommended to receive insulin by a doctor
  • Patients requiring daily finger-stick blood glucose measurements

  • Patients who are on the following drugs and cannot have a substitution (or who decline the substitution):

    • warfarin
    • flecainide
    • methadone
    • amphetamines
    • quinidine
    • chlorpropamide
  • An active cancer, other than the pancreatic cancer, that requires treatment.
  • Enrolled in another therapeutic clinical trial
  • Uncontrolled, intercurrent illness
  • HIV positive individuals undergoing therapy due to known drug:drug interaction between antiretroviral drugs and high-dose ascorbate therapy
  • Women who are nursing

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ascorbate group

Each cycle is 4 calendar weeks

Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Pharmacological ascorbate: 75 grams, three times weekly for 4 weeks
Drug: Gemcitabine

Administered intravenously the same day as nab-paclitaxel and ascorbate Administered after nab-paclitaxel and before ascorbate

  • given for 3 weeks out of the 4 week cycle
  • standard dose reductions are used
  • up to 2 cycles are administered before standard of care CT scan
  • decision to continue therapy is based disease response to therapy as measured from the CT scan
  • treatment continues until disease progression is identified
Other Names:
  • Gemzar
  • Gemcitabine Hydrochloride
Drug: nab-paclitaxel

Administered intravenously the same day as nab-paclitaxel and ascorbate Administered after before gemcitabine and ascorbate

  • given for 3 weeks out of the 4 week cycle
  • standard dose reductions are used
  • up to 2 cycles are administered before standard of care CT scan
  • decision to continue therapy is based disease response to therapy as measured from the CT scan
  • treatment continues until disease progression is identified
Other Names:
  • Abraxane
Drug: Pharmacological ascorbate

Administered intravenously the same day as nab-paclitaxel and gemcitabine Administered after nab-paclitaxel and gemcitabine

  • given 3 times weekly
  • given for 4 weeks out of the 4 week cycle
  • no dose reductions are used
  • up to 2 cycles are administered before standard of care CT scan
  • decision to continue therapy is based disease response to therapy as measured from the CT scan
  • treatment continues until disease progression is identified
Other Names:
  • Vitamin C
  • Ascorbate
  • Ascorbic acid
Active Comparator: Control

Each cycle is 4 calendar weeks

Gemcitabine: 1000 mg/m2, once weekly for 3 weeks nab-paclitaxel: 125 mg/m2, once weekly for 3 weeks Each cycle has 1 rest week
Drug: Gemcitabine

Administered intravenously the same day as nab-paclitaxel and ascorbate Administered after nab-paclitaxel and before ascorbate

  • given for 3 weeks out of the 4 week cycle
  • standard dose reductions are used
  • up to 2 cycles are administered before standard of care CT scan
  • decision to continue therapy is based disease response to therapy as measured from the CT scan
  • treatment continues until disease progression is identified
Other Names:
  • Gemzar
  • Gemcitabine Hydrochloride
Drug: nab-paclitaxel

Administered intravenously the same day as nab-paclitaxel and ascorbate Administered after before gemcitabine and ascorbate

  • given for 3 weeks out of the 4 week cycle
  • standard dose reductions are used
  • up to 2 cycles are administered before standard of care CT scan
  • decision to continue therapy is based disease response to therapy as measured from the CT scan
  • treatment continues until disease progression is identified
Other Names:
  • Abraxane

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Every 2 months for up to 20 years post-treatment
Time, measured in months, from the start of chemotherapy (C1D1) to death from any cause.
Every 2 months for up to 20 years post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor Response
Time Frame: Every 2 months for up to 10 years
Determine the objective response rate of the disease, assessed every 2 months using CT or MRI, and evaluated/defined using the RECIST criteria (v1.1). Results are provided in nominal categories (CR, PR, SD, PD) as per RECIST.
Every 2 months for up to 10 years
Progression free survival
Time Frame: Every 2 months for up to 10 years
Time, measured in days, it takes disease to progress, where disease progression is defined by the RECIST criteria (v1.1). Timeframe is from radiation day 1 to date of disease progression.
Every 2 months for up to 10 years
Adverse event frequency and categorization
Time Frame: Monthly through 30 days after end of treatment.
Categorize and quantify adverse events using the Common Terminology Criteria for Adverse Events (CTCAE v4). Assessments will be monthly through 30 days past the end of therapy.
Monthly through 30 days after end of treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Joseph J. Cullen

Collaborators

National Cancer Institute (NCI)
National Institutes of Health (NIH)
Holden Comprehensive Cancer Center
McGuff Pharmaceuticals, Inc.

Investigators

  • Study Director: Joseph J. Cullen, MD, FACS, University of Iowa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 28, 2018

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

September 14, 2016

First Submitted That Met QC Criteria

September 14, 2016

First Posted (Estimated)

September 19, 2016

Study Record Updates

Last Update Posted (Actual)

October 23, 2023

Last Update Submitted That Met QC Criteria

October 18, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201801759
  • 3P30CA086862 (U.S. NIH Grant/Contract)
  • 5U01CA140206 (U.S. NIH Grant/Contract)
  • P01CA217797 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be shared per consent document, governing Federal regulations and institutional policies, and only after a signed sharing agreement between the sponsor and the requesting investigator.

IPD Sharing Time Frame

Initial requests can be submitted to the sponsor Joseph Cullen, MD, FACS at any time with a description as to the information needed.

IPD Sharing Access Criteria

A signed usage and confidentiality agreement must be executed prior to data sharing.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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