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

Pancreatic Cancer Clinical Trial

Official title:

A Randomized Phase I/II Study With Gemcitabine and RTA 402 or Gemcitabine and Placebo for Patients With Unresectable Pancreatic Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00529113
• Other study ID #: 402-C-0702
• Status: Terminated
• Phase: Phase 1
• Start date: September 30, 2007
• Est. completion date: November 1, 2009

Study information

• Verified date: February 2024
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Terminated
• Enrollment: 33
• Est. completion date: November 1, 2009
• Est. primary completion date: November 1, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• Bardoxolone methyl
Bardoxolone methyl capsules (150 mg/day) for 21 days
• Bardoxolone methyl
Bardoxolone methyl capsules (300 mg/day) for 21 days
• Bardoxolone methyl
Bardoxolone methyl capsules (150 mg/day) for 28 days
• Bardoxolone methyl
Bardoxolone methyl capsules (200 mg/day) for 28 days
• Bardoxolone methyl
Bardoxolone methyl capsules (250 mg/day) for 28 days
• Bardoxolone methyl
Bardoxlone methyl capsules (300 mg/day) x 28 days
• Bardoxolone methyl
Bardoxolone methyl capsules (350 mg/day) x 28 days
• Gemcitabine
1,000 mg/m2 administered as an intravenous infusion on days 1, 8, and 15
• Placebo
Placebo capsules x 28 days
• Bardoxolone methyl
Bardoxolone methyl maximum tolerated dose (as determined in the Phase 1 portion of the study)/day x 28 days

Locations

Country	Name	City	State
United States	Sammons Cancer Center (US Oncology)	Dallas	Texas
United States	Rocky Mountain Cancer Center (US Oncology)	Denver	Colorado
United States	Central Indiana Cancer Centers (US Oncology)	Indianapolis	Indiana
United States	Cancer Centers of Florida (US Oncology)	Ocoee	Florida
United States	Northwest Cancer Specialist- Vancouver Cancer Specialist (US Oncology)	Vancouver	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Reata, a wholly owned subsidiary of Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Phase I - To document any preliminary antitumor activity of RTA 402 in this patient population.		End ofTrial
Secondary	Phase I - To characterize the pharmacokinetics (PK) of RTA 402 in this population.		End of Trial
Secondary	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
Secondary	Phase II - To determine the 1-year survival in this patient population.		End of Trial
Secondary	Phase II - To determine the toxicities of these regimens.		End of Trial
Secondary	Phase II - To determine the changes in quality of life (Functional Assessment of Chronic Illness Therapy (Fatigue), [FACIT-F]).		End of Trial