Gemcitabine, Ascorbate, Radiation Therapy for Pancreatic Cancer, Phase I

NCT01852890 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201310772
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1 (first in man) study testing the safety of adding high dose ascorbate (vitamin C) to standard radiation and chemotherapy for treatment of pancreatic cancer.

Conditions

Pancreatic Neoplasms

Keywords

Ascorbate; Vitamin C; Radiation; Gemcitabine; Ascorbic Acid

Outcome Measures

Primary Outcomes (1)

• Number of grade 3, 4, & 5 adverse events during radiation

  Assess grade 3 and higher adverse events. Evaluate the frequency and severity against the published literature to determine the likely causality between ascorbate and the adverse event(s).

  Weekly during therapy for up to 10 weeks

Secondary Outcomes (3)

• Time to progression

  Monthly, up to 10 years post-treatment

• Overall survival

  Monthly, up to 10 years post-treatment

• Number of grade 3, 4, & 5 adverse events post-treatment

  every 3 months for 2 years

Study Arms (4)

50g Ascorbate

EXPERIMENTAL

This arm is the initial starting dose. The first study participant will be assigned the 50g ascorbate arm. * Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks. * Gemcitabine: 600 mg/m2, once weekly for 6 weeks. * Ascorbate: 50 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.

Drug: Ascorbate; Drug: Gemcitabine; Radiation: Radiation therapy

75g Ascorbate

EXPERIMENTAL

If the 50g arm is tolerated, the study opens the 75g arm. * Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks. * Gemcitabine: 600 mg/m2, once weekly for 6 weeks. * Ascorbate: 75 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.

Drug: Ascorbate; Drug: Gemcitabine; Radiation: Radiation therapy

100g Ascorbate

EXPERIMENTAL

If the 75g arm is tolerated, the study opens the 100g arm. * Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks. * Gemcitabine: 600 mg/m2, once weekly for 6 weeks. * Ascorbate: 100 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.

Drug: Ascorbate; Drug: Gemcitabine; Radiation: Radiation therapy

25g Ascorbate

EXPERIMENTAL

This study arm will only be used if participants cannot tolerate the 50g arm. If participants cannot tolerate 50 grams of Ascorbate, the 25g arm is opened. * Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks. * Gemcitabine: 600 mg/m2, once weekly for 6 weeks. * Ascorbate: 25 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.

Drug: Ascorbate; Drug: Gemcitabine; Radiation: Radiation therapy

Interventions

Ascorbate DRUG

Intravenous infusion of high-dose ascorbate

Also known as: Ascorbic Acid, Vitamin C

100g Ascorbate; 25g Ascorbate; 50g Ascorbate; 75g Ascorbate

Gemcitabine DRUG

Intravenous chemotherapeutic

Also known as: Gemzar

100g Ascorbate; 25g Ascorbate; 50g Ascorbate; 75g Ascorbate

Radiation therapy RADIATION

Also known as: External beam radiation therapy, Intensity modulated radiation therapy, IMRT

100g Ascorbate; 25g Ascorbate; 50g Ascorbate; 75g Ascorbate

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically diagnosed pancreatic adenocarcinoma. Documentation of disease extent by CT scan is required. Radiologically measurable disease is not required.
• Age ≥ 18 years
• ECOG performance status 0, 1, or 2 (Karnofsky \> 50%).
• A complete blood count and differential must be obtained within 21 days prior to radiation fraction 1, with adequate bone marrow functions as defined below:
• Absolute neutrophil count (ANC) ≥ 1500 cells per mm3
• Platelets ≥ 100,000 per mm3
• Leukocytes ≥ 3,000 per mm3
• Serum blood chemistries within 21 days of radiation fraction 1, as defined below:
• Creatinine ≤ 1.5 x UIHC upper limit of normal or creatinine clearance of at least 60 ml/min/1.73 m2 for patients with creatinine levels above institutional normal.
• Total bilirubin ≤ 2 x UIHC upper limit of normal
• ALT ≤ 2.5 times the UIHC upper limit of normal
• AST ≤ 2.5 times the UIHC upper limit of normal
• PT/INR within normal limits (UIHC)
• Tolerate one test dose (15g) of ascorbate.
• Not pregnant.

You may not qualify if:

• G6PD (glucose-6-phosphate dehydrogenase) deficiency.
• Prior abdominal radiotherapy that would result in overlap of fields. The treating radiation oncologist should review prior RT fields as available.
• Adjuvant therapy (including radiation therapy) within 2 calendar weeks. Toxicities from prior therapy for the malignancy should resolve to grade 1 or less.
• Patients actively receiving insulin are excluded.
• Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbate may affect urine acidification and, as a result, may affect clearance rates of these drugs.
• Second malignancy other than non-melanoma skin cancers within the past 5 years.
• Other investigational agents/therapy with the intention to treat the disease under study (observational or imaging trials are acceptable).
• 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 radiation and chemotherapy to a fetus are well documented.
• Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs. A clinical trial designed to address these interaction issues is more appropriate than this phase 1 study.

Sponsors & Collaborators

• Joseph J. Cullen: lead
• Holden Comprehensive Cancer Center: collaborator
• Gateway for Cancer Research: collaborator

Study Sites (1)

The Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Related Publications (5)

• 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.

  PMID: 23381814 BACKGROUND

• Du J, Cullen JJ, Buettner GR. Ascorbic acid: chemistry, biology and the treatment of cancer. Biochim Biophys Acta. 2012 Dec;1826(2):443-57. doi: 10.1016/j.bbcan.2012.06.003. Epub 2012 Jun 20.

  PMID: 22728050 BACKGROUND

• 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.

  PMID: 20400857 BACKGROUND

• 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.

  PMID: 20068072 BACKGROUND

• Mezey E, Potter JJ, French SW, Tamura T, Halsted CH. Effect of chronic ethanol feeding on hepatic collagen in the monkey. Hepatology. 1983 Jan-Feb;3(1):41-4. doi: 10.1002/hep.1840030106.

  PMID: 6295907 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Ascorbic Acid; Gemcitabine; Radiotherapy; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Therapeutics; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted

Study Officials

• Joseph J Cullen, MD, FACS

  The University of Iowa Hospitals & Clinics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 3, 2013
• First Posted: May 14, 2013
• Study Start: January 1, 2014
• Primary Completion: January 22, 2019
• Study Completion: October 14, 2025
• Last Updated: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: After completion of primary outcome.
• Access Criteria: Interested researchers should contact the study PI. A non-disclosure may need to be filed dependent upon data requested.

Locations

US (1)