Saracatinib in Treating Patients With Previously Treated Metastatic Pancreatic Cancer

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

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

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

Study type: Interventional

Funder types: NIH

Identifiers

NCT00735917

P30CA015083 (U.S. NIH Grant/Contract)

MC0547 (Other Identifier)

7602 (Other Identifier)

NCI-2009-00194 (Registry Identifier)

CDR0000610063

MAYO-MC0547

N01CM62205 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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19 participants in 1 patient group

Treatment (enzyme inhibitor therapy)

Experimental group

Description:

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:

Other: pharmacological study

Radiation: fludeoxyglucose F 18

Drug: saracatinib

Other: laboratory biomarker analysis

Other: pharmacogenomic studies

Procedure: positron emission tomography