Study With Gemcitabine and RTA 402 for Patients With Unresectable Pancreatic Cancer

Phase 1

Terminated

• Conditions: Pancreatic Neoplasms; Pancreatic Cancer
• Interventions: Drug: Bardoxolone methyl; Drug: Gemcitabine; Drug: Placebo

• Registration Number: NCT00529113
• Lead Sponsor: 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 Timeline

• Study First Submitted: 2007-09-12
• Study First Submitted QC: 2007-09-12
• Study First Posted: 2007-09-14
• Study Start: 2007-09-30
• Primary Completion: 2009-11-01
• Study Completion: 2009-11-01
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-23
• Last Update Posted: 2025-05-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 33

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.

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