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

NCT00577707 | Completed Phase 2 Results

• 1 other identifier: 07-103
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non Small Cell Lung Cancer; Lung Cancer

Keywords

Lung Cancer; Erlotinib; clinical stage IB-IIIA

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

• 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

Study Arms (1)

Patients With Stage IB-IIIA NSCLC With EGFR Mutations

EXPERIMENTAL

This is a open label, single center, phase II trial for patients with clinical stage IB-IIIA NSCLC (T1-3N0-2M0) who have resectable tumors that harbor EGFR activating mutations. Patients will receive erlotinib x 3 weeks prior to initiation of concurrent erlotinib and chemotherapy.

Drug: erlotinib; Drug: Pemetrexed; Drug: Cisplatin; Procedure: Resection

Interventions

erlotinib DRUG

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.

Patients With Stage IB-IIIA NSCLC With EGFR Mutations

Pemetrexed DRUG

pemetrexed 500 mg/m\^2 every 3 weeks for 4 cycles treatment) on the first day of each cycle of treatment.

Patients With Stage IB-IIIA NSCLC With EGFR Mutations

Cisplatin DRUG

cisplatin 75 mg/m\^2 every 3 weeks for 4 cycles treatment) on the first day of each cycle of treatment.

Patients With Stage IB-IIIA NSCLC With EGFR Mutations

Resection PROCEDURE

Patients With Stage IB-IIIA NSCLC With EGFR Mutations

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Erlotinib Hydrochloride; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Limitations and Caveats

Analysis was not done on the secondary outcomes because of lack of accrual

Results Point of Contact

• Title: Dr. Mark Kris
• Organization: Memorial Sloan Kettering Cancer Center

krism@mskcc.org

646-888-4205

Study Officials

• Naiyer Rizvi, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2007
• First Posted: December 20, 2007
• Study Start: November 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: January 10, 2018
• Results First Posted: November 20, 2015

Record last verified: 2017-12

Locations

US (1)