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

October 18, 2023 updated by: Joseph J. Cullen
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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • The Holden Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Radiation: Radiation therapy
Other Names:
  • IMRT
  • External beam radiation therapy
  • Intensity modulated radiation therapy
Drug: Ascorbate
Intravenous infusion of high-dose ascorbate
Other Names:
  • Vitamin C
  • Ascorbic Acid
Drug: Gemcitabine
Intravenous chemotherapeutic
Other Names:
  • Gemzar
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.
Radiation: Radiation therapy
Other Names:
  • IMRT
  • External beam radiation therapy
  • Intensity modulated radiation therapy
Drug: Ascorbate
Intravenous infusion of high-dose ascorbate
Other Names:
  • Vitamin C
  • Ascorbic Acid
Drug: Gemcitabine
Intravenous chemotherapeutic
Other Names:
  • Gemzar
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.
Radiation: Radiation therapy
Other Names:
  • IMRT
  • External beam radiation therapy
  • Intensity modulated radiation therapy
Drug: Ascorbate
Intravenous infusion of high-dose ascorbate
Other Names:
  • Vitamin C
  • Ascorbic Acid
Drug: Gemcitabine
Intravenous chemotherapeutic
Other Names:
  • Gemzar
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.
Radiation: Radiation therapy
Other Names:
  • IMRT
  • External beam radiation therapy
  • Intensity modulated radiation therapy
Drug: Ascorbate
Intravenous infusion of high-dose ascorbate
Other Names:
  • Vitamin C
  • Ascorbic Acid
Drug: Gemcitabine
Intravenous chemotherapeutic
Other Names:
  • Gemzar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Weekly during therapy for up to 10 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Monthly, up to 10 years post-treatment
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.
Monthly, up to 10 years post-treatment
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).
every 3 months for 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Joseph J. Cullen

Collaborators

Gateway for Cancer Research
Holden Comprehensive Cancer Center

Investigators

  • Principal Investigator: Joseph J Cullen, MD, FACS, The University of Iowa Hospitals & Clinics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2014

Primary Completion (Actual)

January 22, 2019

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

May 3, 2013

First Submitted That Met QC Criteria

May 9, 2013

First Posted (Estimated)

May 14, 2013

Study Record Updates

Last Update Posted (Actual)

October 23, 2023

Last Update Submitted That Met QC Criteria

October 18, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201310772

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Time Frame

After completion of primary outcome.

IPD Sharing Access Criteria

Interested researchers should contact the study PI. A non-disclosure may need to be filed dependent upon data requested.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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