Pancreatic Cancer
Conditions
Keywords
adenocarcinoma of the pancreas, recurrent pancreatic cancer, stage III pancreatic cancer, stage IV pancreatic cancer
Brief summary
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well erlotinib works in treating patients with stage III or stage IV pancreatic cancer.
Detailed description
OBJECTIVES: Primary * Determine the progression-free survival (PFS) of patients with stage III or IV adenocarcinoma of the pancreas treated with erlotinib hydrochloride as first- or second-line therapy. Secondary * Determine the proportion of patients with a radiological response to this drug. * Determine the overall survival of these patients. * Determine the effect of this drug on quality of life in these patients. * Correlate expression of EGFR, E-cadherin, P-cadherin, vimentin, cytokeratin, fibronectin, and ki67 in baseline tumor blocks and presence of K-ras mutations in baseline tumor biopsy specimens with response to this drug. * Correlate smoking status with PFS in patients treated with this drug. * Collect serum samples before, during, and after therapy for future serum proteomic studies and for development of profiles of responders to this drug. OUTLINE: Patients receive oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients complete a questionnaire about their smoking status at baseline. Patients also complete questionnaires about their quality of life every three weeks during study therapy and after completion of study therapy. Blood samples are collected from patients at baseline and periodically during study for future serum proteomic research and for development of profiles of responders to erlotinib hydrochloride therapy. Paraffin-embedded tumor tissue from diagnostic tumor biopsies is assessed at baseline for expression of EGFR, E-cadherin, P-cadherin, vimentin, cytokeratin, fibronectin, and ki67 by immunohistochemical analysis. Tissue from surgical specimens in patients with prior resection is assessed for K-ras mutations by K-ras analysis. After completion of study therapy, patients are followed for at least 6 months. PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.
Interventions
DRUGerlotinib hydrochloride
Oral
OTHERimmunohistochemistry staining method
Correlative Study
OTHERlaboratory biomarker analysis
Correlative Study
Sponsors
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed adenocarcinoma of the pancreas * Locally advanced inoperable or metastatic disease (stage III or IV disease) * No more than 1 prior systemic therapy * Patients who have not received 1 prior systemic therapy must meet 1 of the following criteria: * Ineligible for or refused chemoradiotherapy AND has stage III disease * Ineligible for or refused gemcitabine hydrochloride-based chemotherapy AND has stage IV disease * No brain metastases PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy \> 3 months * WBC \> 3,000/mm³ * ANC \> 1,500/mm³ * Platelet count \> 100,000/mm³ * Bilirubin ≤ 2 mg/dL * AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5 times ULN in patients with documented liver metastases) * Creatinine \< 1.5 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 6 months after completion of study therapy * No uncontrolled comorbid illness that is likely to increase toxicity of the study drug or to interfere with toxicity evaluation * No known allergy to the study drug or its excipients * No symptomatic interstitial pulmonary disease PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Prior adjuvant therapy allowed provided it was completed at least 28 days prior to study entry * No prior EGFR-inhibitor * No concurrent drugs that are known to be strong inducers or inhibitors of the CYP450 enzyme system * No concurrent Hypericum perforatum (St. John's wort) * No concurrent investigational or commercial agents or therapies with the intent to treat the patient's malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Every cycle for up to 52 weeks | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion |
Secondary
| Measure | Time frame |
|---|---|
| Correlation of Response, QOL, and Survival With EGFR, E-cadherin, P-cadherin, Vimentin, Cytokeratin, ki67, and Fibronectin and With Other Prognostic Variables, Such as Age and Tumor Grade | At Baseline |
| Clinical Response (Complete and Partial Response) as Measured by RECIST Criteria | After every cycle |
| Median Overall Survival | After every cycle |
| Change in Quality of Life (QOL) as Measured by EORTC PAN26 Every 3 Weeks During Study Therapy and After Completion of Study Therapy | Every 3 weeks |
| Correlation of Smoking Status With Overall Survival | Every 3 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib (Tarceva) Erlotinib 150mg orally daily for three weeks | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 1 |
| Overall Study | Disease Progression | 13 |
| Overall Study | Other | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Erlotinib (Tarceva) |
|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 10.2 |
| Gender Female | 9 Participants |
| Gender Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 18 |
| serious Total, serious adverse events | 9 / 18 |
Outcome results
Primary
Progression-free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion
Time frame: Every cycle for up to 52 weeks
Population: All treated and eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib (Tarceva) | Progression-free Survival | 1.4 months |
Secondary
Change in Quality of Life (QOL) as Measured by EORTC PAN26 Every 3 Weeks During Study Therapy and After Completion of Study Therapy
Time frame: Every 3 weeks
Population: This study was terminated earlier due to a phase III study that showed this drug was not better than sorafenib so it didn't make sense to offer an inferior drug to patients.
Secondary
Clinical Response (Complete and Partial Response) as Measured by RECIST Criteria
Time frame: After every cycle
Population: This study was terminated earlier due to a phase III study that showed this drug was not better than sorafenib so it didn't make sense to offer an inferior drug to patients.
Secondary
Correlation of Response, QOL, and Survival With EGFR, E-cadherin, P-cadherin, Vimentin, Cytokeratin, ki67, and Fibronectin and With Other Prognostic Variables, Such as Age and Tumor Grade
Time frame: At Baseline
Population: This study was terminated earlier due to a phase III study that showed this drug was not better than sorafenib so it didn't make sense to offer an inferior drug to patients.
Secondary
Correlation of Smoking Status With Overall Survival
Time frame: Every 3 weeks
Population: This study was terminated earlier due to a phase III study that showed this drug was not better than sorafenib so it didn't make sense to offer an inferior drug to patients.
Secondary
Median Overall Survival
Time frame: After every cycle
Population: This study was terminated earlier due to a phase III study that showed this drug was not better than sorafenib so it didn't make sense to offer an inferior drug to patients.