Saracatinib in Treating Patients With Previously Treated Metastatic Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT00735917
• Recruitment Status: Completed
• First Posted: August 15, 2008
• Results First Posted: December 5, 2013
• Last Update Posted: April 2, 2019
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

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.

Condition or disease	Intervention/treatment	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

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of AZD0530 in Previously Treated Metastatic Pancreas Cancer
• Study Start Date: October 2008
• Actual Primary Completion Date: April 2011
• Actual Study Completion Date: October 2012

Arms and Interventions

Arm

Intervention/treatment

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

Outcome Measures

Primary Outcome Measures :

1. Six Month Survival [ Time Frame: Up to 6 months ]
   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 :

1. Overall Survival [ Time Frame: Up to 2 years ]
   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.
2. Confirmed Tumor Responses (Complete Response [CR] or Partial Response [PR]) [ Time Frame: Evaluated using the first 6 courses of treatment ]

   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.

3. 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 ]
   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.
4. Progression-Free Survival [ Time Frame: Progression and survival status assessed every month, up to 2 years ]
   Time from the date of registration to the date of progression or death, whichever occurs first. Estimated by the method of Kaplan-Meier.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Wells Messersmith; Mayo Clinic

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00735917
• Obsolete Identifiers: NCT01647035
• Other Study ID Numbers: NCI-2009-00194; NCI-2009-00194 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); MAYO-MC0547; CDR0000610063; MC0547 ( Other Identifier: Mayo Clinic ); 7602 ( Other Identifier: CTEP ); P30CA015083 ( U.S. NIH Grant/Contract ); N01CM62205 ( U.S. NIH Grant/Contract )
• First Posted: August 15, 2008
• Results First Posted: December 5, 2013
• Last Update Posted: April 2, 2019
• Last Verified: March 2019

Additional relevant MeSH terms:

Pancreatic Neoplasms; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Saracatinib; Fluorodeoxyglucose F18; Radiopharmaceuticals; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Enzyme Inhibitors