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Gemcitabine, Ascorbate, Radiation Therapy for Pancreatic Cancer, Phase I

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01852890
Recruitment Status : Active, not recruiting
First Posted : May 14, 2013
Last Update Posted : March 13, 2019
Sponsor:
Collaborators:
Holden Comprehensive Cancer Center
Gateway for Cancer Research
Information provided by (Responsible Party):
Joseph J. Cullen, University of Iowa

Tracking Information
First Submitted Date  ICMJE May 3, 2013
First Posted Date  ICMJE May 14, 2013
Last Update Posted Date March 13, 2019
Actual Study Start Date  ICMJE January 2014
Actual Primary Completion Date January 22, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2013)
Number of grade 3, 4, & 5 adverse events during radiation [ Time Frame: Weekly during therapy for up to 10 weeks ]
Assess grade 3 and higher adverse events. Evaluate the frequency and severity against the published literature to determine the likely causality between ascorbate and the adverse event(s).
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01852890 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2013)
  • Time to progression [ Time Frame: Monthly, up to 10 years post-treatment ]
    Time from the start of therapy (radiation day 1) to documented disease progression as described by RECIST.
  • Overall survival [ Time Frame: Monthly, up to 10 years post-treatment ]
    From start of treatment (radiation day 1) until the date of death from any cause.
  • Number of grade 3, 4, & 5 adverse events post-treatment [ Time Frame: every 3 months for 2 years ]
    Beginning one month after completing radiation therapy, grade 3 and higher adverse events will be assessed. Evaluate the frequency and severity against the published literature to determine the likely causality between ascorbate and the adverse event(s).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gemcitabine, Ascorbate, Radiation Therapy for Pancreatic Cancer, Phase I
Official Title  ICMJE Gemcitabine, Ascorbate, Radiation Therapy for Pancreatic Cancer, Phase I
Brief Summary This is a phase 1 (first in man) study testing the safety of adding high dose ascorbate (vitamin C) to standard radiation and chemotherapy for treatment of pancreatic cancer.
Detailed Description

This phase 1 study will test the safety of adding high dose ascorbate (vitamin C) to standard chemoradiation. The ascorbate is infused during external beam radiation therapy treatment.

For patients eligible for this trial, standard treatment for their cancer includes radiation therapy combined with weekly gemcitabine (a chemotherapy).

Participants will:

  • receive high doses of intravenous (IV) ascorbate during their daily radiation therapy treatments. Radiation treatments are given once a day, Monday through Friday.
  • have routine doctor's visits and be asked about any side effects they are experiencing.

This is a phase 1 study that will evaluate the side effects of adding ascorbate to standard therapy. The dose given to a participant will be determined by how well other participants have tolerated ascorbate.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Neoplasms
Intervention  ICMJE
  • Drug: Ascorbate
    Intravenous infusion of high-dose ascorbate
    Other Names:
    • Ascorbic Acid
    • Vitamin C
  • Drug: Gemcitabine
    Intravenous chemotherapeutic
    Other Name: Gemzar
  • Radiation: Radiation therapy
    Other Names:
    • External beam radiation therapy
    • Intensity modulated radiation therapy
    • IMRT
Study Arms  ICMJE
  • Experimental: 50g Ascorbate

    This arm is the initial starting dose. The first study participant will be assigned the 50g ascorbate arm.

    • Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
    • Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
    • Ascorbate: 50 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
    Interventions:
    • Drug: Ascorbate
    • Drug: Gemcitabine
    • Radiation: Radiation therapy
  • Experimental: 75g Ascorbate

    If the 50g arm is tolerated, the study opens the 75g arm.

    • Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
    • Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
    • Ascorbate: 75 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
    Interventions:
    • Drug: Ascorbate
    • Drug: Gemcitabine
    • Radiation: Radiation therapy
  • Experimental: 100g Ascorbate

    If the 75g arm is tolerated, the study opens the 100g arm.

    • Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
    • Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
    • Ascorbate: 100 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
    Interventions:
    • Drug: Ascorbate
    • Drug: Gemcitabine
    • Radiation: Radiation therapy
  • Experimental: 25g Ascorbate

    This study arm will only be used if participants cannot tolerate the 50g arm. If participants cannot tolerate 50 grams of Ascorbate, the 25g arm is opened.

    • Radiation: Prescribed to either 50 Gy in 25 fractions or at least 50.4 Gy in 28 fractions, based on tumor. Radiation is delivered 1 fraction/day, 5 days a week, for approximately 5 to 6 weeks.
    • Gemcitabine: 600 mg/m2, once weekly for 6 weeks.
    • Ascorbate: 25 grams administered intravenously (by IV) during radiation therapy, for approximately 5 to 6 weeks.
    Interventions:
    • Drug: Ascorbate
    • Drug: Gemcitabine
    • Radiation: Radiation therapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: December 1, 2017)
16
Original Estimated Enrollment  ICMJE
 (submitted: May 9, 2013)
30
Estimated Study Completion Date  ICMJE January 2020
Actual Primary Completion Date January 22, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must have histologically or cytologically diagnosed pancreatic adenocarcinoma. Documentation of disease extent by CT scan is required. Radiologically measurable disease is not required.
  • Age ≥ 18 years
  • ECOG performance status 0, 1, or 2 (Karnofsky > 50%).
  • A complete blood count and differential must be obtained within 21 days prior to radiation fraction 1, with adequate bone marrow functions as defined below:

    • Absolute neutrophil count (ANC) ≥ 1500 cells per mm3
    • Platelets ≥ 100,000 per mm3
    • Leukocytes ≥ 3,000 per mm3
  • Serum blood chemistries within 21 days of radiation fraction 1, as defined below:

    • Creatinine ≤ 1.5 x UIHC upper limit of normal or creatinine clearance of at least 60 ml/min/1.73 m2 for patients with creatinine levels above institutional normal.
    • Total bilirubin ≤ 2 x UIHC upper limit of normal
    • ALT ≤ 2.5 times the UIHC upper limit of normal
    • AST ≤ 2.5 times the UIHC upper limit of normal
    • PT/INR within normal limits (UIHC)
  • Tolerate one test dose (15g) of ascorbate.
  • Not pregnant.
  • Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  • G6PD (glucose-6-phosphate dehydrogenase) deficiency.
  • Prior abdominal radiotherapy that would result in overlap of fields. The treating radiation oncologist should review prior RT fields as available.
  • Adjuvant therapy (including radiation therapy) within 2 calendar weeks. Toxicities from prior therapy for the malignancy should resolve to grade 1 or less.
  • Patients actively receiving insulin are excluded.
  • Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbate may affect urine acidification and, as a result, may affect clearance rates of these drugs.
  • Second malignancy other than non-melanoma skin cancers within the past 5 years.
  • Other investigational agents/therapy with the intention to treat the disease under study (observational or imaging trials are acceptable).
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness/social situations, or any other condition that would limit compliance with study requirements as determined by study team members.
  • Pregnant or lactating women: The risks of radiation and chemotherapy to a fetus are well documented.
  • Known HIV-positive individuals. High-dose ascorbate acid is a known CYP450 3A4 inducer, which results in lower serum levels of antiretroviral drugs. A clinical trial designed to address these interaction issues is more appropriate than this phase 1 study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01852890
Other Study ID Numbers  ICMJE 201310772
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Data will be shared as per approved IRB application and the subject's opt-in preferences. Data will not be provided from subjects who decline data sharing.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: After completion of primary outcome.
Access Criteria: Interested researchers should contact the study PI. A non-disclosure may need to be filed dependent upon data requested.
Responsible Party Joseph J. Cullen, University of Iowa
Study Sponsor  ICMJE Joseph J. Cullen
Collaborators  ICMJE
  • Holden Comprehensive Cancer Center
  • Gateway for Cancer Research
Investigators  ICMJE
Principal Investigator: Joseph J Cullen, MD, FACS The University of Iowa Hospitals & Clinics
PRS Account University of Iowa
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP