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

• Status: Active, not recruiting
• Trial end date: 2022-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Joseph J. Cullen
• Collaborators: Gateway for Cancer Research; Holden Comprehensive Cancer Center
• Treatments: Ascorbic Acid; Gemcitabine; Vitamins

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.