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

Lung Cancer Clinical Trial

Official title:

A Phase II Study of Erlotinib and Chemotherapy for Patients With Stage IB-IIIA NSCLC With EGFR Mutations (ECON)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00577707
• Other study ID #: 07-103
• Status: Completed
• Phase: Phase 2
• First received: December 18, 2007
• Last updated: December 11, 2017
• Start date: November 2007
• Est. completion date: December 2011

Study information

• Verified date: December 2017
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00602238

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• erlotinib
One tablet daily of erlotinib pills (150 mg daily) for the first 21 days. After surgery, you will be asked to take adjuvant erlotinib 150 mg po daily x 2 years.
• Pemetrexed
pemetrexed 500 mg/m^2 every 3 weeks for 4 cycles treatment) on the first day of each cycle of treatment.
• Cisplatin
cisplatin 75 mg/m^2 every 3 weeks for 4 cycles treatment) on the first day of each cycle of treatment.

Procedure:
• Resection

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Pathologic Complete Response Rate	Complete Response (CR): Disappearance of all clinical evidence of tumor. Partial Response (PR): A 50% or greater decrease in the sum of the products of measured lesions. No simultaneous increase in the size of any lesion or the appearance of new lesions may occur. Non-measurable lesions must remain stable or regress for this category. Minor Response (MR): A > 25% and < 50% decrease in the sum of the products of measured lesions. No simultaneous increase in the size of any lesion or the appearance of new lesions may occur. Non-measurable lesions must remain stable or regress for this category. Stable Disease (SD): A less than 25% decrease. This includes a decrease of less than 25% in the sum of the products of the measured lesions, and any increase of less than 25% in the sum of the products of the measured lesions. There may be no appearance of new disease sites for this category. Progressive Disease (PD): A =25% increase in one or more lesions, or appearance of new lesions.	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.
Secondary	Number of Participants With Response After 21 Days of Single Agent Erlotinib for Stage IB-IIIA NSCLC With a Known EGFR Mutation		calculate the response rate after 21 days of single agent erlotinib
Secondary	Number of Patients With a Response Rate, 3-year Overall Survival and Median Survival of Patients With a Known EGFR Mutation Receiving Neoadjuvant Chemotherapy and Erlotinib (and Adjuvant Erlotinib).		3 years

External Links

•   Memorial Sloan-Kettering Cancer Center