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

Biogen

Status and phase

Terminated

Phase 1

Conditions

Pancreatic Cancer

Pancreatic Neoplasms

Treatments

Drug: Gemcitabine

Drug: Placebo

Drug: Bardoxolone methyl

Study type

Interventional

Funder types

Industry

Identifiers

NCT00529113

402-C-0702

Details and patient eligibility

About

This study assesses the safety and efficacy of RTA 402 in combination with gemcitabine in patients with unresectable pancreatic cancer.

Full 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.

Enrollment

33 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

33 participants in 9 patient groups, including a placebo group

Phase 1 Cohort 1

Experimental group

Description:

Bardoxolone methyl 150 mg/day x 21 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)

Treatment:

Drug: Bardoxolone methyl

Drug: Gemcitabine

Phase 1 Cohort 2

Experimental group

Description:

Bardoxolone methyl 300 mg /day for 21 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)

Treatment:

Drug: Bardoxolone methyl

Drug: Gemcitabine

Phase 1 Cohort 3

Experimental group

Description:

Bardoxolone methyl 150 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)

Treatment:

Drug: Bardoxolone methyl

Drug: Gemcitabine

Phase 1 Cohort 4

Experimental group

Description:

Bardoxolone methyl 200 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)

Treatment:

Drug: Bardoxolone methyl

Drug: Gemcitabine

Phase 1 Cohort 5

Experimental group

Description:

Bardoxolone methyl 250 mg/day for 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)

Treatment:

Drug: Bardoxolone methyl

Drug: Gemcitabine

Phase 1 Cohort 6

Experimental group

Description:

Bardoxolone methyl 300 mg/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)

Treatment:

Drug: Bardoxolone methyl

Drug: Gemcitabine

Phase 1 Cohort 7

Experimental group

Description:

Bardoxolone methyl 350 mg/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)

Treatment:

Drug: Bardoxolone methyl

Drug: Gemcitabine

Phase 2 Cohort 1

Experimental group

Description:

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)

Treatment:

Drug: Bardoxolone methyl

Drug: Gemcitabine

Phase 2 Cohort 2

Placebo Comparator group

Description:

Placebo capsules/day x 28 days and gemcitabine (1000 mg/m2 by intravenous infusion on Days 1, 9, and 15)

Treatment:

Drug: Placebo

Drug: Gemcitabine