Saracatinib in Treating Patients With Previously Treated Metastatic Pancreatic Cancer

Stage IV Pancreatic Cancer Clinical Trial

Official title:

A Phase II Trial of AZD0530 in Previously Treated Metastatic Pancreas Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00735917
• Other study ID #: NCI-2009-00194
• Secondary ID: NCI-2009-00194MA
• Status: Completed
• Phase: Phase 2
• Start date: October 2008
• Est. completion date: October 2012

Study information

• Verified date: March 2019
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT01647035

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: October 2012
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Pancreas
• Pancreatic Neoplasms
• Recurrent Pancreatic Cancer
• Stage IV Pancreatic Cancer

Intervention

Drug:
• saracatinib
Given PO

Other:
• pharmacogenomic studies
Optional correlative studies
• pharmacological study
Optional correlative studies

Procedure:
• positron emission tomography
Optional correlative studies

Radiation:
• fludeoxyglucose F 18
Optional correlative studies

Other:
• laboratory biomarker analysis
Optional correlative studies

Locations

Country	Name	City	State
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Singapore	National University Hospital	Singapore
United States	University of Colorado at Denver	Aurora	Colorado
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 6 months
Secondary	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.	Up to 2 years
Secondary	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.	Evaluated using the first 6 courses of treatment
Secondary	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.	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
Secondary	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.	Progression and survival status assessed every month, up to 2 years