Study With Gemcitabine and RTA 402 for Patients With Unresectable Pancreatic Cancer
- Conditions
- Pancreatic NeoplasmsPancreatic Cancer
- Interventions
- Registration Number
- NCT00529113
- Lead Sponsor
- Reata, a wholly owned subsidiary of Biogen
- Brief Summary
This study assesses the safety and efficacy of RTA 402 in combination with gemcitabine in patients with unresectable pancreatic cancer.
- Detailed Description
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.
Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a wholly owned subsidiary of Biogen.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 33
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1 Cohort 1 Bardoxolone methyl Bardoxolone methyl 150 mg/day x 21 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 1 Gemcitabine Bardoxolone methyl 150 mg/day x 21 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 2 Bardoxolone methyl Bardoxolone methyl 300 mg /day for 21 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 2 Gemcitabine Bardoxolone methyl 300 mg /day for 21 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 3 Gemcitabine Bardoxolone methyl 150 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 4 Bardoxolone methyl Bardoxolone methyl 200 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 5 Gemcitabine Bardoxolone methyl 250 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 6 Bardoxolone methyl Bardoxolone methyl 300 mg/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 7 Bardoxolone methyl Bardoxolone methyl 350 mg/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 2 Cohort 2 Placebo Placebo capsules/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 7 Gemcitabine Bardoxolone methyl 350 mg/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 3 Bardoxolone methyl Bardoxolone methyl 150 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 4 Gemcitabine Bardoxolone methyl 200 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 5 Bardoxolone methyl Bardoxolone methyl 250 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 2 Cohort 1 Bardoxolone methyl Bardoxolone methyl maximum tolerated dose(as determined in the Phase 1 portion of the study)/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 1 Cohort 6 Gemcitabine Bardoxolone methyl 300 mg/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 2 Cohort 1 Gemcitabine Bardoxolone methyl maximum tolerated dose(as determined in the Phase 1 portion of the study)/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15) Phase 2 Cohort 2 Gemcitabine Placebo capsules/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)
- Primary Outcome Measures
Name Time Method Phase I - To determine the maximum tolerated dose (MTD) of RTA 402 in combination with gemcitabine in patients with locally advanced or metastatic pancreatic cancer. End of trial Phase II - To determine if treatment with RTA 402 in combination with gemcitabine can increase the progression-free survival versus gemcitabine plus placebo in patients with unresectable metastatic pancreatic cancer. End of Trial
- Secondary Outcome Measures
Name Time Method Phase I - To document any preliminary antitumor activity of RTA 402 in this patient population. End ofTrial Phase I - To characterize the pharmacokinetics (PK) of RTA 402 in this population. End of Trial Phase II - To determine the overall response rate in patients treated with RTA 402 + gemcitabine and in patients treated with gemcitabine + placebo. End of Trial Phase II - To determine the 1-year survival in this patient population. End of Trial Phase II - To determine the toxicities of these regimens. End of Trial Phase II - To determine the changes in quality of life (Functional Assessment of Chronic Illness Therapy (Fatigue), [FACIT-F]). End of Trial
Trial Locations
- Locations (5)
Central Indiana Cancer Centers (US Oncology)
🇺🇸Indianapolis, Indiana, United States
Rocky Mountain Cancer Center (US Oncology)
🇺🇸Denver, Colorado, United States
Cancer Centers of Florida (US Oncology)
🇺🇸Ocoee, Florida, United States
Northwest Cancer Specialist- Vancouver Cancer Specialist (US Oncology)
🇺🇸Vancouver, Washington, United States
Sammons Cancer Center (US Oncology)
🇺🇸Dallas, Texas, United States