Gemcitabine and Nab-Paclitaxel with or without Pharmacological Ascorbate in Treating Patients with Metastatic Pancreatic Cancer
- Must have cytological or histological diagnosis of adenocarcinoma arising in the pancreas. Adenocarcinoma arising from the Ampullae of Vater is eligible. Diagnosis from metastatic sampling is acceptable
- Disease must be metastatic or node positive
- Recommended to receive gemcitabine and nab-paclitaxel
- Patients must have measurable disease as per RECIST
- Failed initial therapy or ineligible for definitive curative therapy
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky > 50%)
- Platelets >= 100,000/mm^3 (=< 14 days [d] of study day 1)
- Creatinine < 1.5 X institutional upper limit of normal OR creatinine clearance >= 60 mL/(min 1.73 m^2) for patients with creatinine levels above institutional normal (=< 14d of study day 1)
- Not pregnant. A pregnancy test will be obtained at screening per institutional policy
- Agree to birth control. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Prior chemotherapy to treat metastatic pancreatic disease
- Adjuvant therapy (including radiation therapy) within 4 calendar weeks
- Toxicities from prior therapy for the malignancy should resolve to >= grade 2
- G6PD (glucose-6-phosphate dehydrogenase) deficiency
- Patients actively receiving insulin are excluded unless approved by the Investigational New Drug (IND) medical monitor, IND sponsor, and the study principal investigator (PI)
- Patients requiring daily finger-stick blood glucose measurements unless approved by the IND medical monitor, IND sponsor, and the study PI
- Patients who are on warfarin and cannot have a drug substitution or who decline the drug substitution
- Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide. High dose ascorbic acid may affect urine acidification and, as a result, may affect clearance rates of these drugs
- A concurrent malignancy that is clinically actionable or would impact the primary outcome of the clinical trial (a concurrent malignancy whose treatment does not have the potential to interfere with the safety or efficacy of the trial is included as well)
- Enrolled in another clinical trial with a targeted endpoint of treating the patient’s cancer (imaging and biological trials are acceptable)
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection (requiring an inpatient stay or would delay the start of therapy), 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
- Human immunodeficiency virus (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 2 study
- Lactating women: The risks of chemotherapy to a fetus/infant are well documented
I. Determine overall survival in patients when treated with combination gemcitabine hydrochloride (gemcitabine), nab-paclitaxel and high-dose ascorbic acid (P-AscH-) compared to gemcitabine and nab-paclitaxel in patients with non-resectable pancreatic cancer.
I. Determine objective response rate (using Response Evaluation Criteria in Solid Tumors [RECIST] criteria) in patients with non-resectable pancreatic cancer when treated with combination gemcitabine, nab-paclitaxel and P-AscH- compared to gemcitabine and nab-paclitaxel.
II. Determine progression-free survival in patients with non-resectable pancreatic cancer when treated with combination gemcitabine, nab-paclitaxel and P-AscH- compared to gemcitabine and nab-paclitaxel.
III. Categorize and quantify adverse events in subjects when treated with combination gemcitabine, nab-paclitaxel and P-AscH- compared to gemcitabine and nab-paclitaxel in patients with non-resectable pancreatic cancer.
I. Determine change in health related quality of life (HRQOL), if any, during concomitant treatment with P-AscH- using the validated European Organization for Research and Treatment of Cancer (EORTC) questionnaires Quality of Life Questionnaire Core 30 (QLQ-C30).
II. Measure catalase activity in biopsy specimens obtained and correlate catalase levels with overall survival, objective response rate, and progression free survival.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive nab-paclitaxel intravenously (IV) over 30-40 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8 and 15. Patients also receive pharmacological ascorbate IV over 120 minutes thrice weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1, 8 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 28 days, then periodically thereafter.
Trial Phase Phase II
Trial Type Treatment
University of Iowa / Holden Comprehensive Cancer Center
Joseph J. Cullen
- Primary ID 201801759
- Secondary IDs NCI-2018-02701
- Clinicaltrials.gov ID NCT02905578