- To determine the 6-month survival of biomarker-positive patients with previously treated metastatic pancreatic cancer receiving AZD0530.
- To determine the adverse events of this drug in these patients.
- To evaluate the response rate in patients treated with this drug.
- To evaluate the overall survival of patients treated with this drug.
- To explore the pharmacodynamic effects of AZD0530 with optional tumor biopsies, pharmacokinetic studies, and PET scans in a subset of patients.
OUTLINE: This is a multicenter study.
Patients receive oral AZD0530 once daily on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also complete a medication diary.
Periodically, tumor biopsies for pharmacodynamic studies and limited pharmacokinetic blood sampling, plus pharmacogenomic studies are conducted.
After completion of study treatment, patients are followed up for 2 years.
- Histologically or cytologically confirmed adenocarcinoma of the pancreas
- Metastatic disease
- Received ≥ 1 prior chemotherapy regimen, preferably gemcitabine hydrochloride-based
- Biomarker screening portion of study:
- For subjects without archival tissue available (core biopsy or resection specimen; fine-needle aspirate samples only are not sufficient), must be willing to undergo a fresh needle-core biopsy of a safely biopsiable metastasis
- No known brain metastases
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- WBC ≥ 3,000/mm³
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 9 g/dL
- Total bilirubin < 1.5 times upper normal limit (ULN) (patients may have been shunted in order to achieve normal bilirubin level)
- AST or ALT ≤ 2.5 times ULN (< 5 times ULN for patients with liver metastases)
- Creatinine normal OR creatinine clearance ≥ 60 mL/min
- Urine protein < 1,000 mg
- Urine protein:creatinine ratio ≤ 1.0
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Asymptomatic HIV allowed
- Willingness to undergo 2 tumor biopsies
- No history of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530
- No prolonged QTc interval (i.e., ≥ 480 msec)
- No other significant ECG abnormalities
- No poorly controlled hypertension (i.e., systolic blood pressure [BP] ≥ 150 mm Hg or diastolic BP ≥ 90 mm Hg)
- No concurrent cardiac dysfunction including, but not limited to, any of the following:
- History of ischemic heart disease
- Myocardial infarction
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- No condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs ability to swallow AZD0530 tablets
- No uncontrolled concurrent illness including, but not limited to any of the following:
- Ongoing or active infection
- Psychiatric illness or social situations that would limit compliance with study requirements
- No other malignancy within the past 5 years, except curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from all prior therapy (< grade 2) (excluding alopecia) administered within the past 4 weeks
- At least 3 weeks since prior chemotherapy (6 weeks for carmustine or mitomycin)
- At least 4 weeks since prior radiotherapy
- More than 7 days since prior and no concurrent CYP3A4-active agents
- No ongoing adverse events (excluding alopecia) due to chemotherapy or radiotherapy given more than 4 weeks prior to study
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy for HIV-positive patients
- Concurrent low molecular weight heparin or full-dose coumadin allowed
- Concurrent therapeutic hematopoietic growth factors allowed
Last updated: 03/26/2012
NCT ID: NCT00735917