Saracatinib in Treating Patients With Previously Treated Metastatic Pancreatic Cancer

Phase 2

Completed

Conditions: Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer

Interventions: Drug: saracatinib
Other: pharmacogenomic studies
Other: pharmacological study
Procedure: positron emission tomography
Radiation: fludeoxyglucose F 18
Other: laboratory biomarker analysis

Registration Number: NCT00735917

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (enzyme inhibitor therapy)	fludeoxyglucose F 18	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.
Treatment (enzyme inhibitor therapy)	pharmacogenomic studies	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.
Treatment (enzyme inhibitor therapy)	pharmacological study	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.
Treatment (enzyme inhibitor therapy)	positron emission tomography	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.
Treatment (enzyme inhibitor therapy)	laboratory biomarker analysis	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.
Treatment (enzyme inhibitor therapy)	saracatinib	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.

Primary Outcome Measures

Name	Time	Method
Six Month Survival	Up to 6 months	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	Up to 2 years	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.
Confirmed Tumor Responses (Complete Response [CR] or Partial Response [PR])	Evaluated using the first 6 courses of treatment	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.
Duration of Response	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	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.
Progression-Free Survival	Progression and survival status assessed every month, up to 2 years	Time from the date of registration to the date of progression or death, whichever occurs first. Estimated by the method of Kaplan-Meier.

Trial Locations

Locations (9): Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
Sir Charles Gairdner Hospital
🇦🇺
Nedlands, Western Australia, Australia
University of Colorado at Denver
🇺🇸
Aurora, Colorado, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
National University Hospital
🇸🇬
Singapore, Singapore
Mayo Clinic in Florida
🇺🇸
Jacksonville, Florida, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States