A Clinical Trial Evaluating the Effect of Pharmacological Ascorbate on Radiation Therapy for Pancreatic Cancer Patients

NCT03541486 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: XACT-PANC-2
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Radiation therapy improves cancer cure rates by killing cancer cells but it also contributes to long-term side effects in cancer survivors by unintentionally damaging normal organs such as the intestine. This research will what side effects patients with cancer experience, if high dose vitamin C helps reduce these side effects, and if high dose vitamin C increases the survival of patients with pancreatic cancer. We will meet with patients during the study to better understand their experience during their cancer treatment. In the long term, our research could provide a new way help cancer survivors avoid many permanent side effects of cancer treatments.

Conditions

Pancreatic Neoplasm

Keywords

ascorbic acid; ascorbate; sodium ascorbate; radiotherapy; radiotherapy, image-guided; gemcitabine; adverse event; quality of life; radiation enteropathy

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  The study will determine the time (calculated in months) between study day 1 and death from any cause. After 10 years post-treatment, dates will be censored to date of last follow-up

  Up to 5 years post treatment

Secondary Outcomes (8)

• Progression free survival (PFS)

  Up to 5 years post-treatment

• Toxicity over time (ToxT)

  Treatment day 1 to 30 days post-treatment

• Metastasis free survival (MFS)

  Up to 5 years post-treatment

• Resection rate

  Within 2 month post-radiation

• Adverse event frequency and categorization

  Weekly for the first 6 weeks and then at follow-up through 5 years post-treatment

Other Outcomes (1)

• Exploration of patient reported outcomes during combined therapy [qualitative string]

  During treatment phase and up to 5 years post-treatment

Study Arms (2)

Investigational Therapy (ASC)

EXPERIMENTAL

75 grams of pharmacological ascorbate, daily (M-F) 600 mg/m2 of gemcitabine, once a week for up to 6 weeks 50 to 50.4 Gray of radiation therapy delivered using a volumetric arc therapy (VMAT) technique

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

Standard Therapy (ChemoRT)

ACTIVE COMPARATOR

600 mg/m2 of gemcitabine, once a week for up to 6 weeks 50 to 50.4 Gray of radiation therapy delivered using a volumetric arc therapy (VMAT) technique

Drug: Gemcitabine; Radiation: radiation therapy

Interventions

Ascorbate DRUG

75 gram infusion daily (M-F) on days when radiation therapy is administered. The infusion occurs during the 'beam on' of the radiation therapy.

Also known as: Ascor L 500, Pharmacological ascorbate, Vitamin C

Investigational Therapy (ASC)

Gemcitabine DRUG

600 mg/m2 once weekly for up to weeks

Also known as: Gemzar

Investigational Therapy (ASC); Standard Therapy (ChemoRT)

radiation therapy RADIATION

Prescribed to 50 Gy in 25 fractions. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.

Also known as: Volumetric Arc Therapy (VMAT), External beam radiation therapy

Investigational Therapy (ASC); Standard Therapy (ChemoRT)

Eligibility Criteria

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

You may qualify if:

• To be eligible to participate in this study, an individual must meet ALL of the following criteria:
• Ability and willingness to provide informed consent (power of attorney and legally authorized representatives are not accepted for informed consent)
• Stated willingness to comply with all study procedures and availability for duration of the study
• At least 18 years of age
• Histologic or cytologic diagnosis of pancreatic adenocarcinoma
• Referral for gemcitabine-based chemoradiation
• Good performance status (ECOG of 0, 1, or 2; KPS of \> 50)
• No other active malignancy that requires immediate treatment. Slow growing concurrent cancers (such as prostate cancer) are acceptable with appropriate documentation from their treating oncologists for that primary.
• Not experiencing an uncontrolled illness such as infection requiring inpatient admission, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other condition that would limit compliance with the study requirements or unacceptably increase risk to the participant (as determined by study team members).
• Agree to abstain from alcohol and specified over the counter supplements during study treatment

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participating in this study:
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• HIV positive individuals requiring anti-retroviral drug therapy (high-dose ascorbate is known to interact with many of these drugs)
• Platelet count of \<100,000 k/mm3
• Prior radiation that would result in field overlap (this will be determined by the study's radiation oncologist)
• Presence of metastatic disease beyond regional lymphatics
• Actively receiving insulin
• Other therapy (including radiation therapy) within 2 calendar weeks of study therapy
• On any of the following drugs and cannot or will not accept a drug substitution: warfarin, flecainide, methadone, amphetamines, quinidine, and chlorpropamide
• Other investigational agents (PET or SPECT imaging agents are acceptable)
• Other investigational therapy with the intention to treat the disease under study
• Pregnancy
• Individuals declining to use acceptable birth control during the duration of the study
• Lactating women who decline to discontinue breastfeeding their child (women may withhold breast feeding and resume under the direction of their medical oncologist after completion of study)

Sponsors & Collaborators

• Joseph J. Cullen, MD, FACS: lead
• Holden Comprehensive Cancer Center: collaborator

Study Sites (1)

The University of Iowa

Iowa City, Iowa, 52242, United States

Location

Related Publications (5)

• 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

• Tash JS, Means AR. Ca2+ regulation of sperm axonemal motility. Methods Enzymol. 1987;139:808-23. doi: 10.1016/0076-6879(87)39128-1. No abstract available.

  PMID: 3587047 BACKGROUND

• Cantoni C, Bianchi MA, Beretta G, Cerutti F. [Digestibility of uncooked stored ham]. Arch Vet Ital. 1971 Feb 28;22(1):19-26. No abstract available. Italian.

  PMID: 5106370 BACKGROUND

• Hoffman M. [Cardiological findings in adult age]. Pol Tyg Lek. 1969 May 5;24(18):689-92. No abstract available. Polish.

  PMID: 4895694 BACKGROUND

• Alexander MS, Wilkes JG, Schroeder SR, Buettner GR, Wagner BA, Du J, Gibson-Corley K, O'Leary BR, Spitz DR, Buatti JM, Berg DJ, Bodeker KL, Vollstedt S, Brown HA, Allen BG, Cullen JJ. Pharmacologic Ascorbate Reduces Radiation-Induced Normal Tissue Toxicity and Enhances Tumor Radiosensitization in Pancreatic Cancer. Cancer Res. 2018 Dec 15;78(24):6838-6851. doi: 10.1158/0008-5472.CAN-18-1680. Epub 2018 Sep 25.

  PMID: 30254147 BACKGROUND

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 Caster, MD, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Radiologic measurements will be completed by a reviewer blinded to treatment assignment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Randomized trial (standard vs. experimental) in a one-to-one ratio.

Study Record Dates

• First Submitted: April 29, 2018
• First Posted: May 30, 2018
• Study Start: December 31, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Study protocol and consent will be shared after primary completion. Statistical analysis plan will be shared with results reporting. Data are available upon request and will be available for 2 years after the withdraw of the IND.
• Access Criteria: An IRB-stamped signed usage agreement will be required in addition to a data sharing agreement between the academic centers. Interested researchers should contact Dr. Caster or Dr. Cullen

Locations

US (1)