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

Pancreatic Neoplasm Clinical Trial

— XACT-PANC-2  

Official title:

XACT-Pancreas 2: Pharmacological Ascorbate, Gemcitabine, and Radiation Therapy for Pancreatic Cancer, Phase 2

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03541486
• Other study ID #: XACT-PANC-2
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 31, 2025
• Est. completion date: December 31, 2030

Study information

• Verified date: February 2023
• Source: University of Iowa
• Contact: Joseph Caster, MD, PhD
• Phone: 319-353-8836
• Email: joseph-caster[@]uiowa.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 31, 2030
• Est. primary completion date: December 31, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

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)

Related Conditions & MeSH terms

• Pancreatic Neoplasm
• Pancreatic Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	The University of Iowa	Iowa City	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
Joseph J. Cullen, MD, FACS	Holden Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

Cieslak JA, Cullen JJ. Treatment of Pancreatic Cancer with Pharmacological Ascorbate. Curr Pharm Biotechnol. 2015;16(9):759-70. doi: 10.2174/138920101609150715135921. — View 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. — View 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploration of patient reported outcomes during combined therapy [qualitative string]	Semi-structured one-on-one interviews for thematic analysis	During treatment phase and up to 5 years post-treatment
Primary	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	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
Secondary	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
Secondary	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
Secondary	Resection rate	Rate of patients who undergo resection of tumor	Within 2 month post-radiation
Secondary	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
Secondary	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
Secondary	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
Secondary	Pathologic characteristics	• Mucosal ulcerations, inflammatory cell infiltration, collage deposition, and microvascular changes will be assessed	At surgery