Clinical trial NCT00735917: Saracatinib in Treating Patients With Previously Treated Metastatic Pancreatic Cancer
Official title: A Phase II Trial of AZD0530 in Previously Treated Metastatic Pancreas Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-08-15
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Six Month Survival
timeFrame: Up to 6 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to 2 years
measure: Confirmed Tumor Responses (Complete Response [CR] or Partial Response [PR])
timeFrame: Evaluated using the first 6 courses of treatment
measure: Duration of Response
timeFrame: 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
measure: Progression-Free Survival
timeFrame: Progression and survival status assessed every month, up to 2 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Aurora
country: United States
facility: University of Colorado at Denver
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: Mayo Clinic
name: Wells Messersmith
role: PRINCIPAL_INVESTIGATOR
References: