Saracatinib in Treating Patients With Previously Treated Metastatic Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase II Trial of AZD0530 in Previously Treated Metastatic Pancreas Cancer

Conditions
-----------------
Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage IV Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: saracatinib
* Other: pharmacogenomic studies
* Other: pharmacological study
* Procedure: positron emission tomography
* Radiation: fludeoxyglucose F 18
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 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: 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 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: 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 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (enzyme inhibitor therapy)<br>Patients receive saracatinib PO QD on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. | Drug: saracatinib<br>* Given PO<br>* Other names: AZD0530;Other: pharmacogenomic studies<br>* Optional correlative studies<br>* Other names: Pharmacogenomic Study;Other: pharmacological study<br>* Optional correlative studies<br>* Other names: pharmacological studies;Procedure: positron emission tomography<br>* Optional correlative studies<br>* Other names: tomography, emission computed;Radiation: fludeoxyglucose F 18<br>* Optional correlative studies<br>* Other names: FDG;Other: laboratory biomarker analysis<br>* Optional correlative studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six Month Survival | The proportion of successes will be estimated by the number of surviving participants at 6 months divided by the total number of evaluable patients. A confidence interval for the 6-month survival rate was calculated using the exact binomial method. | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival time is defined as the time from registration to death due to any cause. The median survival time and 95% confidence intervals will be estimated using the method of Kaplan-Meier. | Up to 2 years | 
| Confirmed Tumor Responses (Complete Response [CR] or Partial Response [PR]) | A confirmed tumor response is defined to be a CR or PR noted as> the objective status on 2 consecutive evaluations at least 4 weeks apart. Response will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)> > Complete Response (CR): Disappearance of all non-nodal target lesions and each target lymph node must have a reduction in short axis to <1.0 centimeters.> > Partial response (PR): At least a 30% decrease in the sum of the longest diameters of the non-nodal target lesions and the short axes of the target lymph nodes taking as reference the baseline sum of diameters. | Evaluated using the first 6 courses of treatment | 
| Duration of Response | Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. Estimated by the method of Kaplan-Meier. | From the date first objective status is noted to be either a CR or PR to the date progression is documented, assessed up to 2 years | 
| Progression-Free Survival | Time from the date of registration to the date of progression or death, whichever occurs first. Estimated by the method of Kaplan-Meier. | Progression and survival status assessed every month, up to 2 years |