Erlotinib Therapy and Subsequent Development of Mechanisms of Secondary Resistance in Patients With NSCLC

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Genentech
Information provided by (Responsible Party):
David M. Jackman, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00997334
First received: October 16, 2009
Last updated: April 25, 2013
Last verified: April 2013
  Purpose

The purpose of this research study is to assess the frequency of the development of mutations (especially EGFR mutations) that lead to resistance to erlotinib in people with non-small cell lung cancer (NSCLC). The investigators will also be looking to see if the participant's NSCLC improves with erlotinib and why it may eventually stop responding to erlotinib.


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: erlotinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: First-Line Erlotinib Therapy and the Subsequent Development of Mechanisms of Secondary Resistance in Patients With Non-Small Cell Lung Cancer and Known Sensitizing EGFR Mutations

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To prospectively assess the frequency of different genetic mechanisms of secondary resistance in patients' tumors during treatment with erlotinib. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To measure the steady-state plasma concentrations of erlotinib during the course of patients' treatment. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To analyze from both free plasma DNA and DNA from circulating tumor cells of erlotinib-treated patients for the orginal sensitizing EGFR mutations and genetic changes associated with secondary resistance. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • To measure clinical outcomes in patients with known sensitizing mutations in their tumor EGFR when treated with first-line erlotinib. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: December 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: erlotinib
    Taken orally once daily
Detailed Description:
  • Participants will take erlotinib orally once a day. Each treatment cycle lasts 28 days.
  • While on the study, participants will be required to be seen in the clinic on Day 1 of each treatment cycle. During these visit, the following tests and procedures will be done: physical exam and blood tests. They will also return for blood work during Cyle 1 Day 8.
  • At the end of every two cycles an assessment of the participant's tumor will be done by CT and/or MRI (this is part of regular cancer care) as well as the following: Urine test and blood tests.
  • At the end of study treatment the following procedures will be done: blood tests, assessment of the tumor by CT and/or MRI and a new biopsy of the tumor or removal of fluid containing tumor cells.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed non-small cell lung cancer, stage IV or IIIB with a malignant pleural or pericardial effusion. Patients with stage I or II non-small cell lung cancer who have undergone surgical resection but who subsequently relapse with metastatic disease or a malignant pleural effusion are also eligible.
  • Documentation of a sensitizing mutation of the epidermal growth factor receptor. In addition, there must be a sufficient tissue for analysis of KRAS mutations and MET amplification.
  • At least one measurable or evaluable site of disease as defined by revised RECIST (version 1.1) criteria.
  • 18 years of age or older
  • No more than one prior systemic therapy regimen for advanced non-small cell lung cancer. Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC will not count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen.
  • 3 or more weeks since prior major surgery
  • 2 or more weeks since prior radiation
  • ECOG performance status 0-1
  • Life expectancy > 8 weeks
  • Adequate hematologic, renal, and hepatic function
  • Willingness to undergo repeat tumor biopsy at the time of disease progression.

Exclusion Criteria:

  • Untreated and/or uncontrolled central nervous system metastases. Patients with prior brain metastases must have had definitive treatment (radiation or surgery) and must be clinically stable off steroids for at least 1 week prior to enrollment.
  • More than one prior systemic chemotherapy for advanced non-small cell lung cancer. , Chemotherapy delivered as part of concurrent chemoradiation will also count as a prior systemic therapy regimen. Adjuvant therapy for resected NSCLC willnot count towards this total as long as it was completed at least 6 months prior to enrollment and did not include therapy with an EGFR-targeted agent. Adjuvant therapy completed less than 6 months prior to the time of screening will count as a prior regimen.
  • Prior exposure to erlotinib or other treatments targeting the HER family axis.
  • Active malignancies within the past 3 years, except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
  • Any process that compromises the ability to swallow and/or absorb oral medication.
  • A history of any of the following autoimmune skin disorders: Sjogren's syndrome, scleroderma, dermatomyositis, and systemic lupus erythematosus.
  • Significant medical history or unstable medical conditions.
  • Concurrent use of warfarin. Patients must be off warfarin for at least one week prior to initiation of erlotinib. Other non-warfarin anticoagulants are permitted.
  • Patients who require ongoing concomitant use of one of the strong inhibitors/inducers of CYP3A4.
  • Pregnant or breastfeeding. Women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00997334

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
David M. Jackman, MD
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Genentech
Investigators
Principal Investigator: David Jackman, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: David M. Jackman, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00997334     History of Changes
Other Study ID Numbers: 09-210
Study First Received: October 16, 2009
Last Updated: April 25, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
erlotinib
EGFR mutation
NSCLC

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Erlotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014