Gemcitabine, Ascorbate, Radiation Therapy for Pancreatic Cancer, Phase I
Conditions
Pancreatic Neoplasms
Conditions: official terms
Pancreatic Neoplasms
Conditions: Keywords
Ascorbate, Vitamin C, Radiation, Gemcitabine, Ascorbic Acid
Study Type
Interventional
Study Phase
Phase 1
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Ascorbate Type: Drug
Name: Gemcitabine Type: Drug
Name: Radiation therapy Type: Radiation
Overall Status
Recruiting
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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 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.
Location
The Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
Status: Recruiting
Contact: Sandy Vollstedt, RN, BSN - 319-353-7143 - sandy-vollstedt@uiowa.edu
Start Date
January 2014
Completion Date
February 2018
Sponsors
Joseph J. Cullen
Source
University of Iowa
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page