study with gemcitabine and rta 402 for patients with unresectable pancreatic cancer

Conditions: Pancreatic Neoplasms; Pancreatic Cancer

Summary: this study assesses the safety and efficacy of rta 402 in combination with gemcitabine in patients with unresectable pancreatic cancer.

phase i will be conducted to determine the mtd of rta 402 (administered orally days 1-21 or days 1-28 of a 28-day cycle) in combination with gemcitabine (1000 m/m2). gemcitabine will be administered as an intravenous infusion on days 1, 8, and 15 of each 28-day cycle. the phase ii portion of the study will be randomized, and double-blinded. phase ii will utilize the rta 402 mtd determined in phase i; arm 1 will consist of gemcitabine + rta 402. rta 402 capsules will administered orally days 1-21 of each 28-day cycle (or days 1-28 if appropriate, based on phase i results); gemcitabine (1000 mg/m2) will be administered as an intravenous infusion on days 1, 8, and 15 of each 28-day cycle in each arm. arm 2 will consist of gemcitabine + placebo, placebo capsules will be taken orally days 1-21 of each 28-day cycle (or days 1-28 if appropriate, based on phase i results). both treatment arms are 4-weeks in length. the study was conceived with both a phase i and phase ii portion as described above; however, only the phase i portion was completed. the trial was terminated in 2009 before the phase ii portion could begin.

Eligibility criteria:
inclusion criteria: * phase i patients should have treatment naïve pancreatic cancer; however , phase i patients who have had 1 prior regimen consisting of adjuvant chemo-radiation or adjuvant gemcitabine - as defined within the nccn guidelines may be enrolled. phase ii patients must have metastatic disease (stage iv only). * karnofsky performance status of \>70% * adequate liver function. (total bilirubin ≤ 1.5 mg/dl and ast(sgot) and alt(sgpt) of \< 2.5 uln ( ≤ 5 uln for phase ii patients with liver metastases), serum creatinine \< 1.5 uln * adequate bone marrow function as documented by the following laboratory test results within 14 days of starting therapy. platelets ≥100,000/mm3, absolute neutrophil count (anc) ≥1500/mm3, hemoglobin ≥9.0 g/dl, white blood cell (wbc) count ≥3000 /mm3 * practice effective contraception during the entire study period. * life expectancy of more than 3 months. * able and willing to sign the informed consent form. * willing and able to self-administer orally and document all doses of rta 402 ingested. exclusion criteria: * prior treatment for current malignancy outside of the adjuvant setting for phase i * inability to swallow tablets or capsules * active brain metastases or primary central nervous system (cns) malignancies. (patients with a previously treated brain metastasis may be included.) * active second malignancy * ten percent or greater weight loss over the 6 weeks before study entry. * pregnant or breast feeding * clinically significant illnesses which could compromise participation in the study, including, but not limited to: uncontrolled diabetes; active or uncontrolled infection; acute or chronic liver disease; confirmed diagnosis of human immunodeficiency virus (hiv) infection; uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled cardiac arrhythmia. * psychiatric illness that would limit compliance with study requirements.

Keywords: pancreatic cancer gemcitabine