Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer, Lung Cancer, OSI-774, Tarceva, Carboplatin, Paclitaxel, NSCLC
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.
Interventions
150 mg/day, starting day 1 and stopping night prior to surgery.
DRUGPaclitaxel
Planned dose of 200 mg/m\^2 continuous IV infusion over 3 hours on Day 1 of each 21-day cycle.
DRUGCarboplatin
Dose of AUC = 6 mg/ml × min began within 60 minutes following completion of paclitaxel infusion, 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.
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Response | 5 Years to collect outcome information | Response defined by tumor assessment using Response Evaluation Criteria In Solid Tumors (RECIST) to learn effectiveness of Tarceva (OSI-774) when combined with standard chemotherapy before surgery. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: 10/13/2003 to 03/18/2008; All patients recruited at University of Texas M.D. Anderson Cancer Center
Pre-assignment details
Study terminated due to low accrual; No evaluable patients were assigned to Chemotherapy Alone group (anticipated randomization to have been 10 of 40 patients treated with 3 courses of chemotherapy).
Participants by arm
| Arm | Count |
|---|---|
| Chemotherapy + Tarceva | 5 |
| Chemotherapy Alone | 0 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Chemotherapy + Tarceva |
|---|---|---|
| Age, Continuous | 64 years | 64 years |
| Gender Female | 1 participants | 1 participants |
| Gender Male | 4 participants | 4 participants |
| Region of Enrollment United States | 5 participants | 5 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 5 | 0 / 0 |
| serious Total, serious adverse events | 1 / 5 | 0 / 0 |
Outcome results
Primary
Number of Patients With Response
Response defined by tumor assessment using Response Evaluation Criteria In Solid Tumors (RECIST) to learn effectiveness of Tarceva (OSI-774) when combined with standard chemotherapy before surgery.
Time frame: 5 Years to collect outcome information
Population: Analysis limited since of 5 participants enrolled, only 1 evaluable for response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chemotherapy + Tarceva | Number of Patients With Response | Complete Response | 0 Participants |
| Chemotherapy + Tarceva | Number of Patients With Response | Partial Response | 0 Participants |
| Chemotherapy + Tarceva | Number of Patients With Response | Stable Disease | 1 Participants |
| Chemotherapy + Tarceva | Number of Patients With Response | Progressive Disease | 0 Participants |