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

NCT02905578 | Completed Phase 2 DMC FDA Drug

• 4 other identifiers: 2018017593P30CA0868625U01CA140206P01CA217797
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Overall survival

  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 Outcomes (3)

• Tumor Response

  Every 2 months for up to 10 years

• Progression free survival

  Every 2 months for up to 10 years

• Adverse event frequency and categorization

  Monthly through 30 days after end of treatment.

Study Arms (2)

Ascorbate group

EXPERIMENTAL

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; Drug: nab-paclitaxel; Drug: Pharmacological ascorbate

Control

ACTIVE COMPARATOR

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; Drug: nab-paclitaxel

Interventions

Gemcitabine DRUG

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

Also known as: Gemzar, Gemcitabine Hydrochloride

Ascorbate group; Control

nab-paclitaxel DRUG

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

Also known as: Abraxane

Ascorbate group; Control

Pharmacological ascorbate DRUG

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

Also known as: Ascorbate, Vitamin C, Ascorbic acid

Ascorbate group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Joseph J. Cullen: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator
• Holden Comprehensive Cancer Center: collaborator
• McGuff Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Related Publications (3)

• 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.

  PMID: 27833040 BACKGROUND

• 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.

  PMID: 28366679 BACKGROUND

• Bodeker KL, Smith BJ, Berg DJ, Chandrasekharan C, Sharif S, Fei N, Vollstedt S, Brown H, Chandler M, Lorack A, McMichael S, Wulfekuhle J, Wagner BA, Buettner GR, Allen BG, Caster JM, Dion B, Kamgar M, Buatti JM, Cullen JJ. A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer. Redox Biol. 2024 Nov;77:103375. doi: 10.1016/j.redox.2024.103375. Epub 2024 Oct 2.

  PMID: 39369582 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms; Adenocarcinoma

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Ascorbic Acid

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Joseph J. Cullen, MD, FACS

  University of Iowa

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Surgery

Study Record Dates

• First Submitted: September 14, 2016
• First Posted: September 19, 2016
• Study Start: November 28, 2018
• Primary Completion: August 26, 2024
• Study Completion: August 26, 2024
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (1)