Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage IV Pancreatic Cancer
Conditions
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.
Interventions
DRUGsaracatinib
Given PO
OTHERpharmacogenomic studies
Optional correlative studies
OTHERpharmacological study
Optional correlative studies
PROCEDUREpositron emission tomography
Optional correlative studies
RADIATIONfludeoxyglucose F 18
Optional correlative studies
OTHERlaboratory biomarker analysis
Optional correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Six Month Survival | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 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. |
| Confirmed Tumor Responses (Complete Response [CR] or Partial Response [PR]) | 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. |
| Duration of Response | 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. |
| Progression-Free Survival | 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. |
Countries
Australia, Singapore, United States
Participant flow
Recruitment details
Nineteen patients with gemcitabine-resistant metastatic pancreatic cancer were enrolled from four U.S. locations from October 2008 to January 2011.
Pre-assignment details
All 19 patients accrued to this study were used to report endpoints.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Saracatinib) Patients receive 175 mg/day saracatinib orally every day on days 1-28. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Treatment (Saracatinib) |
|---|---|
| Age, Continuous | 63 years |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 19 |
| serious Total, serious adverse events | 13 / 19 |
Outcome results
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.
Time frame: Up to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Saracatinib) | Six Month Survival | 11 percentage of patients |
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.
Time frame: Evaluated using the first 6 courses of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Saracatinib) | Confirmed Tumor Responses (Complete Response [CR] or Partial Response [PR]) | 0 participants |
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.
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
Population: No patients qualified for a confirmed response and therefore this endpoint was not analyzed.
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.
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Saracatinib) | Overall Survival | 2.5 months |
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.
Time frame: Progression and survival status assessed every month, up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Saracatinib) | Progression-Free Survival | 1.6 months |