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A Clinical Trial Evaluating the Effect of Pharmacological Ascorbate on Radiation Therapy for Pancreatic Cancer Patients (XACT-PANC-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03541486
Recruitment Status : Not yet recruiting
First Posted : May 30, 2018
Last Update Posted : February 11, 2022
Sponsor:
Collaborator:
Holden Comprehensive Cancer Center
Information provided by (Responsible Party):
Joseph Caster, Ph.D., M.D., University of Iowa

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.

Condition or disease Intervention/treatment Phase
Pancreatic Neoplasm Drug: Ascorbate Drug: Gemcitabine Radiation: radiation therapy Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized trial (standard vs. experimental) in a one-to-one ratio.
Masking: Single (Outcomes Assessor)
Masking Description: Radiologic measurements will be completed by a reviewer blinded to treatment assignment
Primary Purpose: Treatment
Official Title: XACT-Pancreas 2: Pharmacological Ascorbate, Gemcitabine, and Radiation Therapy for Pancreatic Cancer, Phase 2
Estimated Study Start Date : December 31, 2022
Estimated Primary Completion Date : December 31, 2029
Estimated Study Completion Date : December 31, 2030

Resource links provided by the National Library of Medicine


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.
Other Names:
  • Ascor L 500
  • Pharmacological ascorbate
  • Vitamin C

Drug: Gemcitabine
600 mg/m2 once weekly for up to weeks
Other Name: Gemzar

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.
Other Names:
  • Volumetric Arc Therapy (VMAT)
  • External beam radiation therapy

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
Other Name: Gemzar

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.
Other Names:
  • Volumetric Arc Therapy (VMAT)
  • External beam radiation therapy




Primary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: Up to 5 years post treatment ]
    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


Secondary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: Up to 5 years post-treatment ]
    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.

  2. Toxicity over time (ToxT) [ Time Frame: Treatment day 1 to 30 days post-treatment ]
    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.

  3. Metastasis free survival (MFS) [ Time Frame: Up to 5 years post-treatment ]
    time from treatment initiation (day 1) to the date of first documentation of disease progression outside of the pelvis (per RECIST 1.1)

  4. Resection rate [ Time Frame: Within 2 month post-radiation ]
    Rate of patients who undergo resection of tumor

  5. Adverse event frequency and categorization [ Time Frame: Weekly for the first 6 weeks and then at follow-up through 5 years post-treatment ]
    Categorize and quantify adverse events using the Common Terminology Criteria for Adverse Events (CTCAE, v 5)

  6. Patient reported outcome measure: Vaizey Incontinence questionnaire [ Time Frame: Treatment day 1 to 5 years post-treatment ]
    Patient reported outcome measure of bowel side effects collected at pre-specified timepoints.

  7. Quality of life: Modified Inflammatory Bowel Disease questionnaire [ Time Frame: Treatment day 1 to 5 years post-treatment ]
    Patient completed quality of life form collected at pre-specified timepoints.

  8. Pathologic characteristics [ Time Frame: At surgery ]
    • Mucosal ulcerations, inflammatory cell infiltration, collage deposition, and microvascular changes will be assessed


Other Outcome Measures:
  1. Exploration of patient reported outcomes during combined therapy [qualitative string] [ Time Frame: During treatment phase and up to 5 years post-treatment ]
    Semi-structured one-on-one interviews for thematic analysis



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03541486


Contacts
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Contact: Joseph Caster, MD, PhD 319-353-8836 joseph-caster@uiowa.edu
Contact: Joseph J. Cullen, MD, FACS (319) 353-8297 joseph-cullen@uiowa.edu

Locations
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United States, Iowa
The University of Iowa
Iowa City, Iowa, United States, 52242
Contact: Sandy Vollstedt, RN, BSN, OCN    319-353-7143    sandy-vollstedt@uiowa.edu   
Contact: Heather Brown, RN, BAN, OCN    319-384-7912    heather-brown@uiowa.edu   
Sponsors and Collaborators
Joseph J. Cullen, MD, FACS
Holden Comprehensive Cancer Center
Investigators
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Principal Investigator: Joseph Caster, MD, PhD University of Iowa
Publications:

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Responsible Party: Joseph Caster, Ph.D., M.D., Assistant Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT03541486    
Other Study ID Numbers: XACT-PANC-2
First Posted: May 30, 2018    Key Record Dates
Last Update Posted: February 11, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All collected IPD, including endpoints (OS, PFS, MFS, AE, and PROs), treatment information, coding, code book, and demographics.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joseph Caster, Ph.D., M.D., University of Iowa:
ascorbic acid
ascorbate
sodium ascorbate
radiotherapy
radiotherapy, image-guided
gemcitabine
adverse event
quality of life
radiation enteropathy
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors