Tarceva Surgery for Resectable Stage IIIA(N2) and IIIB (T4 N2) Non-Small-Cell Lung Cancer - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00063258

Purpose

The goal of this clinical research study is to learn about the safety and effectiveness of OSI-774 when combined with standard chemotherapy (carboplatin and paclitaxel) before surgery in the treatment of non-small cell lung cancer.

Condition	Intervention	Phase
Lung Cancer	Drug: OSI-774 Drug: Paclitaxel Drug: Carboplatin	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase II Randomized Open-Label Trial of the EGFR Tyrosine Kinase Inhibitor OSI-774 (Tarceva™) in Combination With Paclitaxel and Carboplatin Prior to Surgery in Resectable Stage IIIA (N2) and IIIB (T4 N2) NSCLC: A Clinical Outcome and Biological Endpoint Trial

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Surgery

Drug Information available for: Paclitaxel Carboplatin Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

To determine the mortality and major morbidity of stage IIIA (N2) and IIIB (T4 N2) NSCLC at thoracotomy of patients following 3 cycles of preoperative chemotherapy with paclitaxel, carboplatin and OSI-774 (Tarceva™). [ Time Frame: Following 3 cycles of treatment ] [ Designated as safety issue: No ]
To evaluate extent of inhibition of EGFR phosphorylation by OSI-774 (Tarceva™) in tumor samples at the time of surgery. [ Time Frame: Tissue obtained for assessment at time of surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine the pathologic complete response rate in stage IIIA (N2) and IIIB (T4 N2) NSCLC patients following 3 cycles of preoperative chemotherapy with paclitaxel, carboplatin and OSI-774. [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
To evaluate the role of selected molecular markers as predictors of response. [ Time Frame: Tissue for molecular studies will be obtained pretreatment either at the time of diagnostic biopsy or mediastinoscopy ] [ Designated as safety issue: No ]
To assess modulation of selected downstream signal transduction elements. [ Time Frame: Tissue for molecular studies will be obtained pretreatment either at the time of diagnostic biopsy or mediastinoscopy ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	June 2003
Study Completion Date:	April 2008
Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Forty patients will be treated with 3 courses of chemotherapy followed by surgery. Ten of these patients will be randomized to chemotherapy alone and 30 patients to chemotherapy plus Tarceva.	Drug: OSI-774 150 mg QD - 150 mg/day, starting day 1 and stopping the night prior to surgery. Drug: Paclitaxel Paclitaxel will be administered by continuous IV infusion over 3 hours on Day 1 of each 21-day cycle at a planned dose of 200 mg/m 2 . Drug: Carboplatin Carboplatin administration at a dose of AUC = 6 mg/ml × min will begin within 60 minutes following completion of the paclitaxel infusion. Carboplatin will be infused over 15-30 minutes on Day 1 of Cycle 1 of each 21-day cycle, and then on Day 1 of each subsequent cycle according to institutional standards.
2: Active Comparator Ten of these patients will be randomized to chemotherapy alone and 30 patients to chemotherapy plus Tarceva.	Drug: OSI-774 150 mg QD - 150 mg/day, starting day 1 and stopping the night prior to surgery. Drug: Paclitaxel Paclitaxel will be administered by continuous IV infusion over 3 hours on Day 1 of each 21-day cycle at a planned dose of 200 mg/m 2 . Drug: Carboplatin Carboplatin administration at a dose of AUC = 6 mg/ml × min will begin within 60 minutes following completion of the paclitaxel infusion. Carboplatin will be infused over 15-30 minutes on Day 1 of Cycle 1 of each 21-day cycle, and then on Day 1 of each subsequent cycle according to institutional standards.

Arms

Assigned Interventions

1: Active Comparator

Forty patients will be treated with 3 courses of chemotherapy followed by surgery. Ten of these patients will be randomized to chemotherapy alone and 30 patients to chemotherapy plus Tarceva.

Drug: OSI-774

150 mg QD - 150 mg/day, starting day 1 and stopping the night prior to surgery.

Drug: Paclitaxel

Paclitaxel will be administered by continuous IV infusion over 3 hours on Day 1 of each 21-day cycle at a planned dose of 200 mg/m 2 .

Drug: Carboplatin

Carboplatin administration at a dose of AUC = 6 mg/ml × min will begin within 60 minutes following completion of the paclitaxel infusion. Carboplatin will be infused over 15-30 minutes on Day 1 of Cycle 1 of each 21-day cycle, and then on Day 1 of each subsequent cycle according to institutional standards.

2: Active Comparator

Ten of these patients will be randomized to chemotherapy alone and 30 patients to chemotherapy plus Tarceva.

Drug: OSI-774

150 mg QD - 150 mg/day, starting day 1 and stopping the night prior to surgery.

Drug: Paclitaxel

Paclitaxel will be administered by continuous IV infusion over 3 hours on Day 1 of each 21-day cycle at a planned dose of 200 mg/m 2 .

Drug: Carboplatin

Carboplatin administration at a dose of AUC = 6 mg/ml × min will begin within 60 minutes following completion of the paclitaxel infusion. Carboplatin will be infused over 15-30 minutes on Day 1 of Cycle 1 of each 21-day cycle, and then on Day 1 of each subsequent cycle according to institutional standards.

Detailed Description:

This is a phase II, single institution open label randomized trial of induction carboplatin and paclitaxel plus/minus daily oral OSI-774 in patients with potentially resectable NSCLC that is stage IIIA and IIIB (T4 satellite nodules or invasion into T4 structures but no malignant effusion.) N3 disease is excluded. Patients will be required to have pathologically demonstrated N2 disease via mediastinoscopy. Forty patients will be treated with 3 courses of chemotherapy followed by surgery. Ten of these patients will be randomized to chemotherapy alone and 30 patients to chemotherapy plus OSI-774. The 10 patients will serve as a chemotherapy alone control for molecular endpoint analysis. OSI-774 will be stopped the night before surgery. At the time of surgery, pathologic response will be determined. Following surgery, patients will be treated with consolidation radiation therapy if there are positive margins or N2 lymph nodes at the time of resection. Patients who have no N2 disease at surgery will have the option of consolidation radiation therapy but will not be required to have it done. Patients not able to tolerate radiation even if they have N2 disease or positive margins at surgery may continue on this study. This will be followed by maintenance OSI-774 for patients from both arms of the study. OSI-774 will be continued as maintenance to a maximum of 2 years following surgery. Tissue for molecular studies will be obtained pretreatment either at the time of diagnostic biopsy or mediastinoscopy. Post-treatment tissue will be obtained at the time of surgery. This tissue will be assayed for defined molecular endpoints using immunohistochemistry, immunoprecipitation and mRNA expression analysis. Blood, urine, hair follicles, and skin samples will also be collected from patients who consent to provide these.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Must have signed consent for LAB03-0383
Pathologic documentation of NSCLC
Stage IIIA and IIIB (T4 satellite nodules or invasion into T4 structures but no malignant effusion) with all patients requiring mediastinoscopy positive N2, potentially resectable disease. N3 disease is excluded.
Measurable disease
Zubrod performance status of 0 or 1
Calculated post-resectional FEV1 of > 40%
No prior chemotherapy or radiation for NSCLC
No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient has been disease-free for at least five years. If patient is suspected or known to have basal or squamous cell skin cancer, this may be treated after induction chemotherapy is completed at the time of thoracotomy.
WBC>4000/ul, ANC>1500/ul, platelets > 100,000/ul
Serum creatinine < 1.5 ULN or calculated creatinine > 50 cc/min
Total serum bilirubin <1.5 x ULN and SGPT or SGOT < 2 X ULN
No post-obstructive pneumonia or other serious infection or other serious underlying medical condition that would impair ability of patient to receive protocol treatment, including prior allergic reactions to drugs containing cremophor.
Pregnant or nursing women may not participate

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00063258

Locations

United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Ralph Zinner, MD

U.T.M.D. Anderson Cancer Center

More Information

No publications provided

Responsible Party:	University of Texas M.D. Anderson Cancer Center ( Ralph Zinner, M.D./Assistant Professor )
Study ID Numbers:	ID02-327
Study First Received:	June 24, 2003
Last Updated:	April 25, 2008
ClinicalTrials.gov Identifier:	NCT00063258 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

Non-Small Cell Lung Cancer
Lung Cancer
OSI-774
Tarceva

Carboplatin
Paclitaxel
NSCLC

Additional relevant MeSH terms:

Erlotinib
Thoracic Neoplasms
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Enzyme Inhibitors
Antimitotic Agents
Carboplatin
Protein Kinase Inhibitors
Pharmacologic Actions

Carcinoma
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Lung Neoplasms
Paclitaxel
Therapeutic Uses
Lung Diseases
Tubulin Modulators
Antineoplastic Agents, Phytogenic
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 22, 2009