Erlotinib and Chemotherapy for Operable Stage IB-IIIA Non-Small Cell Lung Cancer (NSCLC) Patients With Less Than or Equal 15 Pack Year Smoking History - Full Text View

Sponsors and Collaborators:	Memorial Sloan-Kettering Cancer Center Genentech
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00577707

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. Erlotinib (TarcevaTM) is a newer drug which has shown some benefit for patients with non-small cell lung cancer in clinical trials. Many different types of cancer cells, including your type of lung cancer, have a receptor on their surface called the epidermal growth factor receptor (EGFR). 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. We will also be looking for changes in the EGFR and KRAS genes from your tumor after it has been removed. KRAS is a gene that has been associated with resistance to erlotinib.

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 II

MedlinePlus related topics: Cancer Lung Cancer Smoking

Drug Information available for: Cisplatin Pemetrexed disodium Pemetrexed Erlotinib Erlotinib hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Efficacy Study
Official Title:	A Phase II Study of Erlotinib and Chemotherapy for Operable Stage IB-IIIA NSCLC Patients With Less Than or Equal 15 Pack Year Smoking History (ECON)

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

Primary Outcome Measures:

To determine the pathologic complete response rate for stage IB-IIIA NSCLC patients (never smoker/oligo-smoker) (NS/OS) 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 < 15 pack year smoking history (NS/OS). [ Time Frame: calculate the response rate after 21 days of single agent erlotinib ] [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	November 2007
Estimated Study Completion Date:	November 2010
Estimated Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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 chemotherapy 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.

Arms

Assigned Interventions

1: Experimental

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 chemotherapy 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 in patients with NSCLC who have no history of smoking (NS) or a < 15 pack year smoking history (oligo-smokers) (OS). The rationale for studying only NS/OS is that this patient population is most likely to benefit from EGFR TKI therapy in combination with chemotherapy based on data from the advanced NSCLC patient population and based on published data showing correlation with the number of (#) pack years smoked and the presence or absence of an EGFR mutation.

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 be non-smoker or have had less than or equal to 15 pack year smoking
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00577707

Contacts

Contact: Naiyer Rizvi, MD	212-639-3204	rizvin@mskcc.org
Contact: Mark Kris, MD	212-639-7590	krism@mskcc.org

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Naiyer Rizvi, MD 212-639-3204 rizvin@mskcc.org
Contact: Mark Kris, MD 212-639-2939 krism@mskcc.org
Principal Investigator: Naiyer Rizvi, MD

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Genentech

Investigators

Principal Investigator:

Naiyer Rizvi, MD

Memorial Sloan-Kettering Cancer Center

More Information

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Naiyer Rizvi, MD )
Study ID Numbers:	07-103
Study First Received:	December 18, 2007
Last Updated:	January 8, 2009
ClinicalTrials.gov Identifier:	NCT00577707
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Lung Cancer
Erlotinib
clinical stage IB-IIIA

Study placed in the following topic categories:

Thoracic Neoplasms
Erlotinib
Non-small cell lung cancer
Carcinoma
Pemetrexed
Folic Acid
Smoking

Respiratory Tract Diseases
Cisplatin
Lung Neoplasms
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Antimetabolites
Respiratory Tract Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors

Folic Acid Antagonists
Protein Kinase Inhibitors
Pharmacologic Actions
Habits
Neoplasms
Neoplasms by Site
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 16, 2009