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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Iowa
Sponsor:
Information provided by (Responsible Party):
Joseph J. Cullen, University of Iowa
ClinicalTrials.gov Identifier:
NCT01852890
First received: May 3, 2013
Last updated: January 21, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Pancreatic Neoplasms
Drug: Ascorbate
Drug: Gemcitabine
Radiation: Radiation therapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Gemcitabine, Ascorbate, Radiation Therapy for Pancreatic Cancer, Phase I

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • Number of grade 3, 4, & 5 adverse events during radiation [ Time Frame: Weekly during therapy for up to 10 weeks ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Time to progression [ Time Frame: Monthly, up to 10 years post-treatment ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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).


Estimated Enrollment: 30
Study Start Date: January 2014
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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
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.
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
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.
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01852890

Locations
United States, Iowa
The Holden Comprehensive Cancer Center Recruiting
Iowa City, Iowa, United States, 52242
Contact: Sandy Vollstedt, RN, BSN    319-353-7143    sandy-vollstedt@uiowa.edu   
Contact: Bryan Allen, MD, PhD    (319) 356-3693    bryan-allen@uiowa.edu   
Principal Investigator: Joseph J. Cullen, MD         
Sub-Investigator: Daniel Berg, M.D.         
Sub-Investigator: John M. Buatti, M.D.         
Sub-Investigator: Garry R. Buettner, Ph.D.         
Sub-Investigator: Mark C. Smith, M.D.         
Sub-Investigator: Carryn M. Anderson, M.D.         
Sub-Investigator: Wenqing Sun, M.D., Ph.D.         
Sub-Investigator: Bryan Allen, M.D., Ph.D.         
Sub-Investigator: William Rockey, M.D., Ph.D.         
Sub-Investigator: Douglas Spitz, Ph.D.         
Sub-Investigator: Brett Wagner, M.A.         
Sub-Investigator: Sam Schroeder, B.S.         
Sub-Investigator: Ray Hohl, M.D., Ph.D.         
Sponsors and Collaborators
Joseph J. Cullen
Investigators
Principal Investigator: Joseph J. Cullen, MD The University of Iowa Hospitals & Clinics
  More Information

Publications:
Responsible Party: Joseph J. Cullen, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT01852890     History of Changes
Other Study ID Numbers: GAX-PAN-I
Study First Received: May 3, 2013
Last Updated: January 21, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Iowa:
Ascorbate
Vitamin C
Radiation
Gemcitabine
Ascorbic Acid

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Ascorbic Acid
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Antioxidants
Protective Agents
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on September 18, 2014