Saracatinib in Treating Patients With Previously Treated Metastatic Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00735917
First received: August 14, 2008
Last updated: April 25, 2014
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage IV Pancreatic Cancer
Drug: saracatinib
Other: pharmacogenomic studies
Other: pharmacological study
Procedure: positron emission tomography
Radiation: fludeoxyglucose F 18
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of AZD0530 in Previously Treated Metastatic Pancreas Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Six Month Survival [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    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:
  • Overall Survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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]) [ Time Frame: Evaluated using the first 6 courses of treatment ] [ Designated as safety issue: No ]

    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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Progression and survival status assessed every month, up to 2 years ] [ Designated as safety issue: No ]
    Time from the date of registration to the date of progression or death, whichever occurs first. Estimated by the method of Kaplan-Meier.


Enrollment: 19
Study Start Date: October 2008
Study Completion Date: October 2012
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy)
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
Given PO
Other Name: AZD0530
Other: pharmacogenomic studies
Optional correlative studies
Other Name: Pharmacogenomic Study
Other: pharmacological study
Optional correlative studies
Other Name: pharmacological studies
Procedure: positron emission tomography
Optional correlative studies
Other Names:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed
Radiation: fludeoxyglucose F 18
Optional correlative studies
Other Names:
  • 18FDG
  • FDG
Other: laboratory biomarker analysis
Optional correlative studies

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00735917

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Colorado
University of Colorado at Denver
Aurora, Colorado, United States, 80045
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Michigan
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Australia, Western Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
Singapore
National University Hospital
Singapore, Singapore, 119074
Sponsors and Collaborators
Investigators
Principal Investigator: Wells Messersmith Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00735917     History of Changes
Obsolete Identifiers: NCT01647035
Other Study ID Numbers: NCI-2009-00194, NCI-2009-00194, MAYO-MC0547, CDR0000610063, MC0547, 7602, P30CA015083, N01CM62205
Study First Received: August 14, 2008
Results First Received: October 7, 2013
Last Updated: April 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Fluorodeoxyglucose F18
Saracatinib
Radiopharmaceuticals
Diagnostic Uses of Chemicals
Pharmacologic Actions
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014