S0709: Erlotinib With or Without Carboplatin and Paclitaxel in Stage IIIB or Stage IV Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving erlotinib together with carboplatin and paclitaxel may kill more tumor cells. PURPOSE: This randomized phase II trial is studying how well erlotinib works when given alone or together with carboplatin and paclitaxel in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Detailed Description
-----------------
OBJECTIVES: Primary To select a regimen (erlotinib hydrochloride with or without carboplatin and paclitaxel) for further testing against standard treatment, based on median progression-free survival for ≥ 3 months, in patients with stage IIIB or IV non-small cell lung cancer with a Zubrod performance status of 2. Secondary To assess the feasibility of selecting patients for a trial based on central EGFR testing of serum in a cooperative group setting. To evaluate the objective tumor response rates (confirmed and unconfirmed, complete and partial response), in a subset of patients with measurable disease. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and oral erlotinib hydrochloride once daily on days 2-16. Treatment repeats every 21 days for 4 courses. Beginning in course 5 and for all subsequent courses, patients receive oral erlotinib hydrochloride alone on days 1-21. Courses with erlotinib hydrochloride repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 2 years.

Official Title
-----------------
A Phase II Selection Design of Pharmacodynamic Separation of Carboplatin/Paclitaxel/OSI-774 (Erlotinib; NSC-718781) or OSI-774 Alone in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients With Performance Status 2 (PS-2)

Conditions
-----------------
Lung Cancer

Intervention / Treatment
-----------------
* Drug: carboplatin
* Drug: erlotinib hydrochloride
* Drug: paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including any of the following subtypes: Adenocarcinoma Large cell carcinoma Squamous cell carcinoma Unspecified Newly diagnosed primary disease OR recurrent disease after prior surgery and/or radiotherapy, meeting 1 of the following staging criteria: Selected stage IIIB disease (T4 [secondary to malignant pleural effusion only], any N, M0) Stage IV disease (any T, any N, M1 [distant metastases present]) Measurable or nonmeasurable disease by CT scan, MRI, x-ray, physical exam, or nuclear scan The CT scan from a combined PET/CT scan may only be used to document nonmeasurable disease Pleural effusions, ascites, and laboratory parameters are not acceptable as the only evidence of disease Shows evidence of EGFR tyrosine kinase inhibitor therapy benefit (i.e., proteomics positive) prior to study registration No untreated brain metastases Patients with treated brain metastases are allowed provided metastases have remained controlled for at least two weeks following treatment, AND patient has no residual neurological dysfunction off corticosteroids Patients with neurologic abnormalities on physical examination or symptoms must have a negative pretreatment CT or MRI scan of the brain 28 days prior to registration PATIENT CHARACTERISTICS: Zubrod performance status 2 ANC ≥ 1,500/mm³ Platelet count ≥ 1,000/mm³ Serum bilirubin normal SGOT or SGPT normal Serum creatinine ≤ 2 times upper limit of normal OR creatinine clearance ≥ 50 mL/min Willing to provide prior smoking history as requested on the prestudy form No gastrointestinal (GI) tract disease resulting in an inability to take enteral medication No malabsorption syndrome or requirement for IV alimentation No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis) No significant history of cardiac disease, including any of the following: Uncontrolled high blood pressure Unstable angina Congestive heart failure Myocardial infarction within the past 6 months Cardiac ventricular arrhythmia requiring medication No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 3 weeks since prior radiotherapy or surgery (thoracic or other major surgery) and recovered At least 1 year since prior adjuvant chemotherapy No prior systemic hormonal therapy, chemotherapy, or biological therapy for advanced NSCLC No prior EGFR inhibitors No prior surgical procedures affecting absorption No concurrent major surgery

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients receive oral erlotinib hydrochloride once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: erlotinib hydrochloride<br>* given orally<br>|
| Active Comparator: Arm II<br>Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and oral erlotinib hydrochloride once daily on days 2-16. Treatment repeats every 21 days for 4 courses. Beginning in course 5 and for all subsequent courses, patients receive oral erlotinib hydrochloride alone on days 1-21. Courses with erlotinib hydrochloride repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: carboplatin<br>* given IV<br>Drug: erlotinib hydrochloride<br>* given orally<br>Drug: paclitaxel<br>* given IV<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Selection of One of Two Treatment Regimens (Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel) for Further Study in a Phase III Trial, Based on Median Progression-free Survival for ≥ 3 Months |  | From date of registration to 3 years or death, whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (Confirmed and Unconfirmed, Complete and Partial Response) in a Subset of Patients With Measurable Disease | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | From date of registration to 3 years or death, whichever comes first | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, adenocarcinoma of the lung, large cell lung cancer, squamous cell lung cancer