Clinical trial NCT00470535: Erlotinib in Treating Patients With Stage III or Stage IV Pancreatic Cancer
Official title: Phase II Study of Erlotinib (Tarceva®) in Patients With Advanced Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas
recurrent pancreatic cancer
stage III pancreatic cancer
stage IV pancreatic cancer
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
First posted: 2007-05-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Progression-free Survival
timeFrame: Every cycle for up to 52 weeks
Secondary outcomes:
measure: Clinical Response (Complete and Partial Response) as Measured by RECIST Criteria
timeFrame: After every cycle
measure: Median Overall Survival
timeFrame: After every cycle
measure: Change in Quality of Life (QOL) as Measured by EORTC PAN26 Every 3 Weeks During Study Therapy and After Completion of Study Therapy
timeFrame: Every 3 weeks
measure: Correlation of Smoking Status With Overall Survival
timeFrame: Every 3 weeks
measure: 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
timeFrame: At Baseline
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Renuka Iyer, MD
role: PRINCIPAL_INVESTIGATOR
References: