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

Primary Purpose

Pancreatic Neoplasms, Cancer of Pancreas, Cancer of the Pancreas

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Gemcitabine

nab-paclitaxel

Pharmacological ascorbate

About this trial

This is an interventional treatment trial for Pancreatic Neoplasms focused on measuring Ascorbate, Vitamin C, Pharmacological ascorbate, Pharmacologic ascorbate, Ascorbic Acid, gemcitabine, nab-paclitaxel, Gemzar, Abraxane

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Holden Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ascorbate group

Control

Arm Description

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

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

Outcomes

Primary Outcome Measures

Overall survival

Time, measured in months, from the start of chemotherapy (C1D1) to death from any cause.

Secondary Outcome Measures

Tumor Response

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.

Progression free survival

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.

Adverse event frequency and categorization

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.

Full Information

NCT ID

NCT02905578

First Posted

September 14, 2016

Last Updated

October 18, 2023

Sponsor

Joseph J. Cullen

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT02905578

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

November 28, 2018 (Actual)

Primary Completion Date

December 31, 2025 (Anticipated)

Study Completion Date

December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Joseph J. Cullen

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pancreatic Neoplasms, Cancer of Pancreas, Cancer of the Pancreas, Neoplasms, Pancreatic, Pancreas Cancer, Pancreas Neoplasms, Adenocarcinoma

Keywords

Ascorbate, Vitamin C, Pharmacological ascorbate, Pharmacologic ascorbate, Ascorbic Acid, gemcitabine, nab-paclitaxel, Gemzar, Abraxane

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

65 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ascorbate group

Arm Type

Experimental

Arm Description

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

Arm Title

Control

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

Gemzar, Gemcitabine Hydrochloride

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

nab-paclitaxel

Other Intervention Name(s)

Abraxane

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Pharmacological ascorbate

Other Intervention Name(s)

Ascorbate, Vitamin C, Ascorbic acid

Intervention Description

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

Primary Outcome Measure Information:

Title

Overall survival

Description

Time, measured in months, from the start of chemotherapy (C1D1) to death from any cause.

Time Frame

Every 2 months for up to 20 years post-treatment

Secondary Outcome Measure Information:

Title

Tumor Response

Description

Time Frame

Every 2 months for up to 10 years

Title

Progression free survival

Description

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.

Time Frame

Every 2 months for up to 10 years

Title

Adverse event frequency and categorization

Description

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.

Time Frame

Monthly through 30 days after end of treatment.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joseph J. Cullen, MD, FACS

Organizational Affiliation

University of Iowa

Official's Role

Study Director

Facility Information:

Facility Name

Holden Comprehensive Cancer Center

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

Citations:

PubMed Identifier

27833040

Citation

Doskey CM, Buranasudja V, Wagner BA, Wilkes JG, Du J, Cullen JJ, Buettner GR. Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy. Redox Biol. 2016 Dec;10:274-284. doi: 10.1016/j.redox.2016.10.010. Epub 2016 Oct 28.

Results Reference

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PubMed Identifier

26081808

Citation

Du J, Cieslak JA 3rd, Welsh JL, Sibenaller ZA, Allen BG, Wagner BA, Kalen AL, Doskey CM, Strother RK, Button AM, Mott SL, Smith B, Tsai S, Mezhir J, Goswami PC, Spitz DR, Buettner GR, Cullen JJ. Pharmacological Ascorbate Radiosensitizes Pancreatic Cancer. Cancer Res. 2015 Aug 15;75(16):3314-26. doi: 10.1158/0008-5472.CAN-14-1707. Epub 2015 Jun 16.

Results Reference

background

PubMed Identifier

28366679

Citation

Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer-Morales KL, Furqan M, Sandhu S, Carlisle TL, Smith MC, Abu Hejleh T, Berg DJ, Zhang J, Keech J, Parekh KR, Bhatia S, Monga V, Bodeker KL, Ahmann L, Vollstedt S, Brown H, Shanahan Kauffman EP, Schall ME, Hohl RJ, Clamon GH, Greenlee JD, Howard MA, Schultz MK, Smith BJ, Riley DP, Domann FE, Cullen JJ, Buettner GR, Buatti JM, Spitz DR, Allen BG. O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate. Cancer Cell. 2017 Apr 10;31(4):487-500.e8. doi: 10.1016/j.ccell.2017.02.018. Epub 2017 Mar 30. Erratum In: Cancer Cell. 2017 Aug 14;32(2):268.

Results Reference

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

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