Clinical trial NCT00529113: Study With Gemcitabine and RTA 402 for Patients With Unresectable Pancreatic Cancer
Official title: A Randomized Phase I/II Study With Gemcitabine and RTA 402 or Gemcitabine and Placebo for Patients With Unresectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pancreatic Neoplasms
Pancreatic Cancer
Keywords: pancreatic cancer
gemcitabine
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2007-09-14
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: End of trial
measure: 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.
timeFrame: End of Trial
Secondary outcomes:
measure: Phase I - To document any preliminary antitumor activity of RTA 402 in this patient population.
timeFrame: End ofTrial
measure: Phase I - To characterize the pharmacokinetics (PK) of RTA 402 in this population.
timeFrame: End of Trial
measure: Phase II - To determine the overall response rate in patients treated with RTA 402 + gemcitabine and in patients treated with gemcitabine + placebo.
timeFrame: End of Trial
measure: Phase II - To determine the 1-year survival in this patient population.
timeFrame: End of Trial
measure: Phase II - To determine the toxicities of these regimens.
timeFrame: End of Trial
measure: Phase II - To determine the changes in quality of life (Functional Assessment of Chronic Illness Therapy (Fatigue), [FACIT-F]).
timeFrame: End of Trial
Other outcomes:
Locations:
city: Denver
country: United States
facility: Rocky Mountain Cancer Center (US Oncology)
state: Colorado
city: Ocoee
country: United States
facility: Cancer Centers of Florida (US Oncology)
state: Florida
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers (US Oncology)
state: Indiana
city: Dallas
country: United States
facility: Sammons Cancer Center (US Oncology)
state: Texas
city: Vancouver
country: United States
facility: Northwest Cancer Specialist- Vancouver Cancer Specialist (US Oncology)
state: Washington
Study officials:
References: