Study With Gemcitabine And RTA 402 For Patients With Unresectable Pancreatic Cancer

Study Overview

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

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.

Pancreatic Neoplasms
Pancreatic Cancer

DRUG: Bardoxolone methyl
DRUG: Bardoxolone methyl
DRUG: Bardoxolone methyl
DRUG: Bardoxolone methyl
DRUG: Bardoxolone methyl
DRUG: Bardoxolone methyl
DRUG: Bardoxolone methyl
DRUG: Gemcitabine
DRUG: Placebo
DRUG: Bardoxolone methyl

402-C-0702

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2007-09-12	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-05-23
First Submitted that Met QC Criteria 2007-09-12	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-05-29
First Posted (ACTUAL) 2007-09-14	Results First Posted N/A	Last Verified 2025-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Phase 1 Cohort 1 Bardoxolone methyl 150 mg/day x 21 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)	DRUG: Bardoxolone methyl Bardoxolone methyl capsules (150 mg/day) for 21 days DRUG: Gemcitabine 1,000 mg/m2 administered as an intravenous infusion on days 1, 8, and 15
EXPERIMENTAL: Phase 1 Cohort 2 Bardoxolone methyl 300 mg /day for 21 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)	DRUG: Bardoxolone methyl Bardoxolone methyl capsules (300 mg/day) for 21 days DRUG: Gemcitabine 1,000 mg/m2 administered as an intravenous infusion on days 1, 8, and 15
EXPERIMENTAL: Phase 1 Cohort 3 Bardoxolone methyl 150 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)	DRUG: Bardoxolone methyl Bardoxolone methyl capsules (150 mg/day) for 28 days DRUG: Gemcitabine 1,000 mg/m2 administered as an intravenous infusion on days 1, 8, and 15
EXPERIMENTAL: Phase 1 Cohort 4 Bardoxolone methyl 200 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)	DRUG: Bardoxolone methyl Bardoxolone methyl capsules (200 mg/day) for 28 days DRUG: Gemcitabine 1,000 mg/m2 administered as an intravenous infusion on days 1, 8, and 15
EXPERIMENTAL: Phase 1 Cohort 5 Bardoxolone methyl 250 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)	DRUG: Bardoxolone methyl Bardoxolone methyl capsules (250 mg/day) for 28 days DRUG: Gemcitabine 1,000 mg/m2 administered as an intravenous infusion on days 1, 8, and 15
EXPERIMENTAL: Phase 1 Cohort 6 Bardoxolone methyl 300 mg/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)	DRUG: Bardoxolone methyl Bardoxlone methyl capsules (300 mg/day) x 28 days DRUG: Gemcitabine 1,000 mg/m2 administered as an intravenous infusion on days 1, 8, and 15
EXPERIMENTAL: Phase 1 Cohort 7 Bardoxolone methyl 350 mg/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)	DRUG: Bardoxolone methyl Bardoxolone methyl capsules (350 mg/day) x 28 days DRUG: Gemcitabine 1,000 mg/m2 administered as an intravenous infusion on days 1, 8, and 15
EXPERIMENTAL: Phase 2 Cohort 1 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)	DRUG: Gemcitabine 1,000 mg/m2 administered as an intravenous infusion on days 1, 8, and 15 DRUG: Bardoxolone methyl Bardoxolone methyl maximum tolerated dose (as determined in the Phase 1 portion of the study)/day x 28 days
PLACEBO_COMPARATOR: Phase 2 Cohort 2 Placebo capsules/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)	DRUG: Gemcitabine 1,000 mg/m2 administered as an intravenous infusion on days 1, 8, and 15 DRUG: Placebo Placebo capsules x 28 days

Primary Outcome Measures	Measure Description	Time Frame
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	Measure Description	Time Frame
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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications

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