A Clinical Trial Evaluating The Effect Of Pharmacological Ascorbate On Radiation Therapy For Pancreatic Cancer Patients

Study Overview

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

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.

This is a randomized phase 2 study is designed to determine initial efficacy and assess adverse events, and quantify pathologic evidence of intestinal radiation injury. The ascorbate is infused before, during, and after the external beam radiation therapy treatment. Each ascorbate infusion is 75 grams (roughly the same amount of vitamin C from 1,000 oranges). For patients eligible for this trial, standard treatment for their cancer includes radiation therapy combined with weekly gemcitabine (a chemotherapy). Participants will: * be randomized (like flipping a coin) to receive the investigational treatment (pharmacological ascorbate plus gemcitabine plus radiation) or standard treatment only (gemcitabine plus radiation) * receive gemcitabine (a chemotherapy) once a week for up to 6 weeks of therapy (all participants) * receive radiation treatments are given once a day, Monday through Friday (all participants). * have routine doctor's visits and be asked about any side effects they are experiencing (all participants). * be interviewed to discuss their side effects, how it impacts their life, and describe their recent activities. * receive pharmacological ascorbate intravenously ascorbate during their daily radiation therapy treatments (if randomized to receive the investigational treatment). Once the patient completes radiation, the ascorbate infusions are also completed. However, the patient will need to return for regular follow-up care at University of Iowa. We are interested in the long-term side effects of radiation - which may not develop for years - so it is important the participant return to radiation oncology for follow-up. We will also conduct interviews at that time to review the side effects and how they impact the participant's quality of life.

Pancreatic Neoplasm

DRUG: Ascorbate
DRUG: Gemcitabine
RADIATION: radiation therapy

XACT-PANC-2

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2018-04-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-03-05
First Submitted that Met QC Criteria 2018-05-22	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-03-10
First Posted (ACTUAL) 2018-05-30	Results First Posted N/A	Last Verified 2025-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
Single

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Investigational Therapy (ASC) 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 75 gram infusion daily (M-F) on days when radiation therapy is administered. The infusion occurs during the 'beam on' of the radiation therapy. DRUG: Gemcitabine 600 mg/m2 once weekly for up to weeks RADIATION: radiation therapy Prescribed to 50 Gy in 25 fractions. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
ACTIVE_COMPARATOR: Standard Therapy (ChemoRT) 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 600 mg/m2 once weekly for up to weeks RADIATION: radiation therapy Prescribed to 50 Gy in 25 fractions. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Investigational Therapy (ASC)

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

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

DRUG: Gemcitabine

600 mg/m2 once weekly for up to weeks

RADIATION: radiation therapy

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

ACTIVE_COMPARATOR: Standard Therapy (ChemoRT)

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

600 mg/m2 once weekly for up to weeks

RADIATION: radiation therapy

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

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
Progression free survival (PFS)	From radiation day 1 to documented disease progression in CT imaging as described by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Measured in months.	Up to 5 years post-treatment
Toxicity over time (ToxT)	Toxicity over time will be assessed by summarizing treatment emergent adverse events by system organ class and/or preferred term, type of adverse event, and severity. Elapsed days of toxicity will be summarized.	Treatment day 1 to 30 days post-treatment
Metastasis free survival (MFS)	time from treatment initiation (day 1) to the date of first documentation of disease progression outside of the pelvis (per RECIST 1.1)	Up to 5 years post-treatment
Resection rate	Rate of patients who undergo resection of tumor	Within 2 month post-radiation
Adverse event frequency and categorization	Categorize and quantify adverse events using the Common Terminology Criteria for Adverse Events (CTCAE, v 5)	Weekly for the first 6 weeks and then at follow-up through 5 years post-treatment
Patient reported outcome measure: Vaizey Incontinence questionnaire	Patient reported outcome measure of bowel side effects collected at pre-specified timepoints.	Treatment day 1 to 5 years post-treatment
Quality of life: Modified Inflammatory Bowel Disease questionnaire	Patient completed quality of life form collected at pre-specified timepoints.	Treatment day 1 to 5 years post-treatment
Pathologic characteristics	• Mucosal ulcerations, inflammatory cell infiltration, collage deposition, and microvascular changes will be assessed	At surgery

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Holden Comprehensive Cancer Center

Investigators

PRINCIPAL_INVESTIGATOR: Joseph Caster, MD, PhD, University of Iowa

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

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