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

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ClinicalTrials.gov Identifier: NCT02905578
Recruitment Status : Recruiting
First Posted : September 19, 2016
Last Update Posted : September 26, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Holden Comprehensive Cancer Center
McGuff Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Joseph J. Cullen, University of Iowa

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Pancreatic Neoplasms Cancer of Pancreas Cancer of the Pancreas Neoplasms, Pancreatic Pancreas Cancer Pancreas Neoplasms Adenocarcinoma Drug: Gemcitabine Drug: nab-paclitaxel Drug: Pharmacological ascorbate Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Pharmacological Ascorbate, Gemcitabine, and Nab-Paclitaxel for Metastatic Pancreatic Cancer (PACMAN 2.1)
Actual Study Start Date : November 5, 2018
Estimated Primary Completion Date : February 10, 2025
Estimated Study Completion Date : December 31, 2025


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 Name: 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:
  • Ascorbate
  • Vitamin C
  • 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 Name: Abraxane




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • 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
  • 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

If all of the above are met, the potential participant will receive a 15 gram challenge dose of ascorbate via intravenous infusion. This is the final screening procedure.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02905578


Contacts
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Contact: Joseph J. Cullen, MD, FACS 319-353-8297 joseph-cullen@uiowa.edu
Contact: Daniel J. Berg, MD 319-353-7800 daniel-j-berg@uiowa.edu

Locations
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United States, Iowa
Holden Comprehensive Cancer Center Recruiting
Iowa City, Iowa, United States, 52242
Contact: Sandy Vollstedt, RN, BSN, OCN    319-353-7143    sandy-vollstedt@uiowa.edu   
Contact: Heather Brown, RN, BAN, OCN    (319) 384-7912    heather-brown@uiowa.edu   
Sub-Investigator: Daniel Berg, MD         
Principal Investigator: Joseph Cullen, MD         
Sponsors and Collaborators
Joseph J. Cullen
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Holden Comprehensive Cancer Center
McGuff Pharmaceuticals, Inc.
Investigators
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Study Director: Joseph J. Cullen, MD, FACS University of Iowa

Publications:
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Responsible Party: Joseph J. Cullen, Professor, Department of Surgery, University of Iowa
ClinicalTrials.gov Identifier: NCT02905578     History of Changes
Other Study ID Numbers: 201801759
3P30CA086862 ( U.S. NIH Grant/Contract )
5U01CA140206 ( U.S. NIH Grant/Contract )
First Posted: September 19, 2016    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
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.
Access Criteria: A signed usage and confidentiality agreement must be executed prior to data sharing.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joseph J. Cullen, University of Iowa:
Ascorbate
Vitamin C
Pharmacological ascorbate
Pharmacologic ascorbate
Ascorbic Acid
gemcitabine
nab-paclitaxel
Gemzar
Abraxane
Additional relevant MeSH terms:
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Adenocarcinoma
Pancreatic Neoplasms
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Vitamins
Ascorbic Acid
Gemcitabine
Paclitaxel
Albumin-Bound Paclitaxel
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents