Clinical trial NCT03541486: A Clinical Trial Evaluating the Effect of Pharmacological Ascorbate on Radiation Therapy for Pancreatic Cancer Patients
Official title: XACT-Pancreas 2: Pharmacological Ascorbate, Gemcitabine, and Radiation Therapy for Pancreatic Cancer, Phase 2
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Pancreatic Neoplasm
Keywords: ascorbic acid
ascorbate
sodium ascorbate
radiotherapy
radiotherapy, image-guided
gemcitabine
adverse event
quality of life
radiation enteropathy
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: Holden Comprehensive Cancer Center
First posted: 2018-05-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized trial (standard vs. experimental) in a one-to-one ratio.
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 5 years post treatment
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: Up to 5 years post-treatment
measure: Toxicity over time (ToxT)
timeFrame: Treatment day 1 to 30 days post-treatment
measure: Metastasis free survival (MFS)
timeFrame: Up to 5 years post-treatment
measure: Resection rate
timeFrame: Within 2 month post-radiation
measure: Adverse event frequency and categorization
timeFrame: Weekly for the first 6 weeks and then at follow-up through 5 years post-treatment
measure: Patient reported outcome measure: Vaizey Incontinence questionnaire
timeFrame: Treatment day 1 to 5 years post-treatment
measure: Quality of life: Modified Inflammatory Bowel Disease questionnaire
timeFrame: Treatment day 1 to 5 years post-treatment
measure: Pathologic characteristics
timeFrame: At surgery
Other outcomes:
measure: Exploration of patient reported outcomes during combined therapy [qualitative string]
timeFrame: During treatment phase and up to 5 years post-treatment
Locations:
city: Iowa City
country: United States
facility: The University of Iowa
state: Iowa
Study officials:
affiliation: University of Iowa
name: Joseph Caster, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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