Clinical trial NCT00063258: Tarceva Surgery for Resectable Stage IIIA(N2) and IIIB (T4 N2) Non-Small-Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: Non-Small Cell Lung Cancer
Lung Cancer
OSI-774
Tarceva
Carboplatin
Paclitaxel
NSCLC
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2003-06-25
Enrollment: 5
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 criteria: Inclusion Criteria:

1. Must have signed consent for LAB03-0383
2. Pathologic documentation of NSCLC
3. 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.
4. Measurable disease
5. Zubrod performance status of 0 or 1
6. Calculated post-resectional FEV1 of \> 40%
7. WBC\>4000/l, ANC\>1500/l, platelets \> 100,000/l
8. Serum creatinine \< 1.5 ULN or calculated creatinine \> 50 cc/min
9. Total serum bilirubin \<1.5 x ULN or SGPT or SGOT \< 2 X ULN
10. The following must be completed within 28 days of registration: CT scan of the chest and upper abdomen to include the adrenals. Mediastinoscopy to document ipsilateral nodal involvement and exclude N3 disease Blood tests, and pulmonary function tests The following must be completed within 2 months of registration: Pet scan If a CT PET is done more than 28 days, only the CT needs to be repeated and a bone scan to rule out bone metastases

Exclusion Criteria:

1. No prior chemotherapy or radiation for NSCLC
2. 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 skin cancer, this maybe treated after induction chemotherapy is completed at the time of thoracotomy.
3. 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.
4. Pregnant or nursing women may not participate

Primary outcomes:
measure: Number of Patients With Response
timeFrame: 5 Years to collect outcome information
Secondary outcomes:
Other outcomes:
Locations:
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Ralph Zinner, MD
role: PRINCIPAL_INVESTIGATOR
References: