Saracatinib in Treating Patients With Previously Treated Metastatic Pancreatic Cancer
Primary Purpose
Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage IV Pancreatic Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
saracatinib
pharmacogenomic studies
pharmacological study
positron emission tomography
fludeoxyglucose F 18
laboratory biomarker analysis
Sponsored by
About this trial
This is an interventional treatment trial for Adenocarcinoma of the Pancreas
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
Sites / Locations
- Mayo Clinic in Arizona
- University of Colorado at Denver
- Mayo Clinic in Florida
- Wayne State University/Karmanos Cancer Institute
- Mayo Clinic
- Washington University School of Medicine
- University of Wisconsin Hospital and Clinics
- Sir Charles Gairdner Hospital
- National University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (enzyme inhibitor therapy)
Arm 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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
NCT ID
NCT00735917
First Posted
August 14, 2008
Last Updated
March 20, 2019
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00735917
Brief Title
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
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
October 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage IV Pancreatic Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (enzyme inhibitor therapy)
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
saracatinib
Other Intervention Name(s)
AZD0530
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
pharmacogenomic studies
Other Intervention Name(s)
Pharmacogenomic Study
Intervention Description
Optional correlative studies
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Optional correlative studies
Intervention Type
Procedure
Intervention Name(s)
positron emission tomography
Other Intervention Name(s)
FDG-PET, PET, PET scan, tomography, emission computed
Intervention Description
Optional correlative studies
Intervention Type
Radiation
Intervention Name(s)
fludeoxyglucose F 18
Other Intervention Name(s)
18FDG, FDG
Intervention Description
Optional correlative studies
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Optional correlative studies
Primary Outcome Measure Information:
Title
Six Month Survival
Description
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.
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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.
Time Frame
Up to 2 years
Title
Confirmed Tumor Responses (Complete Response [CR] or Partial Response [PR])
Description
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.
Time Frame
Evaluated using the first 6 courses of treatment
Title
Duration of Response
Description
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.
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
Title
Progression-Free Survival
Description
Time from the date of registration to the date of progression or death, whichever occurs first. Estimated by the method of Kaplan-Meier.
Time Frame
Progression and survival status assessed every month, up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wells Messersmith
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
University of Colorado at Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Facility Name
Wayne State University/Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
National University Hospital
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
12. IPD Sharing Statement
Learn more about this trial
Saracatinib in Treating Patients With Previously Treated Metastatic Pancreatic Cancer
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