A Phase II Trial of AZD0530 in Previously Treated Metastatic Pancreas Cancer
A Phase II Trial of AZD0530 in Previously Treated Metastatic Pancreas Cancer
This phase II trial is studying how well saracatinib works in treating patients with previously treated metastatic pancreatic cancer. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:
I. To determine the 6-month survival of biomarker-positive patients with previously treated metastatic pancreatic cancer receiving AZD0530 (saracatinib).
II. To determine the adverse events of this drug in these patients.
SECONDARY OBJECTIVES:
I. To evaluate the response rate in patients treated with this drug. II. To evaluate the overall survival of patients treated with this drug. III. To explore the pharmacodynamic effects of AZD0530 with optional tumor biopsies, pharmacokinetic studies, and positron emission tomography (PET) scans in a subset of patients.
OUTLINE:
Patients receive saracatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 2 years.
Inclusion Criteria:
Histologically or cytologically confirmed adenocarcinoma of the pancreas
Received ≥ 1 prior chemotherapy regimen, preferably gemcitabine hydrochloride-based
Biomarker screening portion of study:
No known brain metastases
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%
White blood cell (WBC) ≥ 3,000/mm³
Absolute neutrophil count (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)
Aspartate aminotransferase (AST) or alanine aminotransferase (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 human immunodeficiency virus (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 electrocardiogram (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:
No condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or requirement for intravenous (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:
No other malignancy within the past 5 years, except curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix
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 cytochrome P450 3A4 (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