Erlotinib in Treating Patients With Stage III or Stage IV Pancreatic Cancer

Phase II Study of Erlotinib (Tarceva®) in Patients With Advanced Pancreatic Adenocarcinoma

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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: erlotinib hydrochloride; Other: immunohistochemistry staining method

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - Oral Erlotinib hydrochloride; 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	Other: laboratory biomarker analysis; Correlative Study; Drug: erlotinib hydrochloride; Oral; Other: immunohistochemistry staining method; Correlative Study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Every cycle for up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Renuka Iyer, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: May 3, 2007
• First Submitted That Met QC Criteria: May 3, 2007
• First Posted (Estimate): May 7, 2007

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: January 9, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: recurrent pancreatic cancer; adenocarcinoma of the pancreas; stage IV pancreatic cancer; stage III pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: CDR0000543406; RPCI-I-87106