Erlotinib and Chemotherapy for Patients With Stage IB-IIIA NSCLC With EGFR Mutations (ECON)

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00577707
First received: December 18, 2007
Last updated: December 15, 2011
Last verified: December 2011
  Purpose

The purpose of this study is to try to improve the odds that your cancer may be cured. Pemetrexed and cisplatin are traditional chemotherapy drugs that have been shown to help some patients with non-small cell lung cancer. Many different types of cancer cells, including your type of lung cancer, have a protein on their surface called the epidermal growth factor receptor (EGFR). Stimulation of these receptors can result in growth of cancer cells and progression of cancer. In addition, your cancer has an EGFR mutation (a specific abnormality in the genetic code for EGFR). Erlotinib (TarcevaTM) is a newer drug which has shown benefit for patients with lung cancers that contain an EGFR mutation. Erlotinib works by blocking this receptor and depriving the cancer cells of this message to grow and multiply. In this research study, we plan to combine erlotinib with traditional chemotherapy drugs to see if the combination works better than chemotherapy alone.

The main purpose of this research is to find out the good and bad effects that the combination of these 3 drugs (pemetrexed, cisplatin and erlotinib) has when given to patients with early stage non-small cell lung cancer before surgery. A secondary purpose is to find out the good and bad effects that occur when erlotinib is given to patients after surgery for 2 years.


Condition Intervention Phase
Non Small Cell Lung Cancer
Lung Cancer
Drug: pemetrexed, cisplatin and erlotinib before surgery then erlotinib is given to patients after surgery for 2 years
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Erlotinib and Chemotherapy for Patients With Stage IB-IIIA NSCLC With EGFR Mutations (ECON)

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine the pathologic complete response rate for patients with stage IB-IIIA NSCLC with tumors that harbor an EGFR mutation treated with neoadjuvant chemotherapy + erlotinib [ Time Frame: Patients will undergo a CT scan of chest every 3 months for year 1 and every 4 months for year 2. In years 3 and 4, a chest CT or chest x-ray every 6 months. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the response rate after 21 days of single agent erlotinib for stage IB-IIIA NSCLC with a known EGFR mutation. [ Time Frame: calculate the response rate after 21 days of single agent erlotinib ] [ Designated as safety issue: No ]
  • To determine the response rate, 3-year overall survival and median survival of patients with stage IB-IIIA NSCLC with a known EGFR mutation receiving neoadjuvant chemotherapy and erlotinib (and adjuvant erlotinib). [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: November 2007
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Erlotinib and chemotherapy for operable stage IB-IIIA NSCLC patients with less than or equal to 15 pack year smoking history
Drug: pemetrexed, cisplatin and erlotinib before surgery then erlotinib is given to patients after surgery for 2 years
One tablet daily of erlotinib pills (150 mg daily) for the first 21 days on this study and then a CT scan will be performed. After the CT scan you will start treatment with intravenous pemetrexed and cisplatin (pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 every 3 weeks for 4 cycles treatment) on the first day of each cycle of treatment. The duration of each cycle is 21 days. You will receive treatment for 4 cycles. You will be asked to stop taking the erlotinib at least 2 days before surgery. After surgery, you will be asked to take adjuvant erlotinib 150 mg po daily x 2 years.

Detailed Description:

Chemotherapy and surgery in combination represents the standard of care for patients with resectable stage IB-IIIA NSCLC. However, the 5-year survival continues to be disappointing despite this standard of care. This study incorporates targeted therapy with an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) as part of a multimodality strategy for stage IB-IIIA resectable NSCLC tumors with a known EGFR activating mutation. The rationale for including only patients with EGFR mutations is based on recent data that reported that patients with advanced NSCLC whose tumor harbor EGFR activating mutations had an objective response rate of 71% with gefitinib compared with a 1% objective response rate in patients with EGFR wild-type tumors.

  Eligibility

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

Inclusion Criteria:

  • Pathologic confirmation of NSCLC
  • Patients must have previously untreated stage IB-IIIA NSCLC (T1-3N0-2M0)
  • Patients must have lung cancer with a documented EGFR activating mutation (exon 19 deletion, L858R, L861Q)
  • Patients must be candidates for resection with curative intent
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded on CT)
  • Age greater or equal to 18 years
  • Karnofsky performance status greater or equal to 70%
  • Normal marrow function: leukocytes greater than or equal to 3,000/μl, absolute neutrophil count greater than or equal to 1,500/μl, platelets greater than or equal to 100,000/μl, hemoglobin greater than or equal to 9 gm/dl
  • Adequate renal function, with creatinine less than or equal to 1.3 mg/dl or calculated creatinine clearance greater to or equal to 60ml/min by Cockroft and Gault equation using parameters of age, weight (kg), and baseline serum creatinine (mg/dl)
  • Adequate hepatic function: Total bilirubin within normal limits, AST < 1.5 X UNL, alkaline phosphatase < 1.5 X UNL
  • Women of childbearing age must have a negative urine or blood pregnancy test
  • Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
  • Patients must have ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Prior chemotherapy or radiation therapy, with the exception of chemotherapy for nononcologic conditions (ie, methotrexate for the treatment of rheumatoid arthritis)
  • Prior treatment with gefitinib, erlotinib, or other drugs that target EGFR
  • Patients must not be receiving any other investigational agents
  • Any evidence of interstitial lung disease (patients with chronic stable radiographic changes who are asymptomatic need not be excluded)
  • Patients who report a hearing deficit at baseline, even if it does not require a hearing aid or intervention, or interfere with activities of daily life (CTCAE grade 2 or higher)
  • Peripheral neuropathy > grade 1
  • Known HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with the study drugs.
  • Other serious illness or medical condition including unstable cardiac disease requiring treatment, history of significant neurologic or psychiatric disorders (including psychotic disorders, dementia, or seizures), or active uncontrolled infection
  • Women who are pregnant or breast-feeding
  • Psychiatric illness or social situation that would limit compliance with study requirements
  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: NCT00577707

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Genentech
Investigators
Principal Investigator: Naiyer Rizvi, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00577707     History of Changes
Obsolete Identifiers: NCT00602238
Other Study ID Numbers: 07-103
Study First Received: December 18, 2007
Last Updated: December 15, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Lung Cancer
Erlotinib
clinical stage IB-IIIA

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Cisplatin
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014