Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well docetaxel given together with cisplatin and pegfilgrastim followed by erlotinib hydrochloride works in treating patients with stage IIIB or stage IV non-small cell lung cancer. Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Colony stimulating factors, such as pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving dose-dense combination chemotherapy together with pegfilgrastim and erlotinib hydrochloride may kill more tumor cells

Detailed Description
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PRIMARY OBJECTIVES: I. To determine if this regimen improves the time-to-progression for patients with advanced non-small cell lung cancer (NSCLC) compared to historical controls. SECONDARY OBJECTIVES: I. To assess response rate and median survival. II. To evaluate tumor biomarkers that could predict response and survival for patients treated with this regimen including endothelial growth factor receptor (EGFR) expression, EGFR Fluorescence in situ hybridization (FISH), and k-ras mutations. III. To evaluate genetic polymorphisms as markers of response and survival for patients treated with this regimen including polymorphisms in XPD, XRCC1, XRCC3, and cyclin D1. OUTLINE: Patients receive docetaxel intravenously (IV) over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously (SC) on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive erlotinib hydrochloride orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year and every 6 months for 2 years.

Official Title
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Phase II Study of Sequential Dose-Dense Chemotherapy and Dose-Intense Erlotinib for the Initial Treatment of Advanced Non-Small Cell Lung Cancer

Conditions
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Adenocarcinoma of the Lung, Adenosquamous Cell Lung Cancer, Bronchoalveolar Cell Lung Cancer, Large Cell Lung Cancer, Non-small Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer, Squamous Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Biological: pegfilgrastim
* Drug: erlotinib hydrochloride
* Other: laboratory biomarker analysis
* Genetic: polymorphism analysis
* Other: pharmacogenomic studies
* Genetic: genetic linkage analysis
* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic Documentation: Either histologic or cytologic documentation of non-small cell carcinoma (NSCLC) is necessary, and the following diagnostic categories are acceptable: squamous carcinoma, basaloid carcinoma, adenocarcinoma, bronchioloalveolar carcinoma, adenosquamous carcinoma, large cell carcinoma (not neuroendocrine), sarcomatoid carcinoma, and non-small cell carcinoma not otherwise specified (NOS); histologic or cytologic documentation of recurrence is required in patients who were previously completely resected Advanced Disease: Stage IIIB because of malignant pleural or pericardial effusion or stage IV disease Patients must be ineligible for Avastin or decline treatment with Avastin Prior Treatment: No prior chemotherapy or treatment with an EGFR inhibitor is allowed; brain metastasis must be under control (patient neurologically stable) All Patients must have Measurable or Non-Measurable Disease: measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension; the longest diameter of measurable lesions must be >= 20 mm with conventional techniques or >= 10 mm with spiral computed tomography (CT) scan; non-measurable disease includes the following: Bone lesions Brain metastasis or leptomeningeal disease Ascites Pleural/pericardial effusion Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Tumor lesions situated in a previously irradiated area Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 Granulocytes >= 1,500/ul Platelets >= 100,000/ul Creatinine =< upper limit of normal (ULN) Bilirubin =< 1.5 mg/dl Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 1.5 x ULN Alkaline (Alk.) phosphatase (phos.) =< 2.5 x ULN Patients must provide verbal and written informed consent to participate in the study Exclusion Criteria: Patients who are pregnant or nursing because of significant risk to the fetus/infant Patients with neuropathy >= grade 2 Patients with a psychiatric illness which would prevent the patient from giving informed consent Patients who are unable to take oral medications Women with child-bearing potential or men who are sexual partners of women with child-bearing potential who are not willing to practice adequate contraceptive measures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (chemo, chemoprotection, antiangiogenesis therapy)<br>Patients receive docetaxel IV over 1 hour on day 1, cisplatin IV over 1 hour on day 1, and pegfilgrastim subcutaneously on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 weeks after completion of docetaxel, cisplatin, and pegfilgrastim, patients receive oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity. | Drug: cisplatin<br>* Given IV<br>* Other names: DDP;Biological: pegfilgrastim<br>* Given SC<br>* Other names: SD-01 sustained duration G-CSF;Drug: erlotinib hydrochloride<br>* Given PO<br>* Other names: OSI-774;Other: laboratory biomarker analysis<br>* Optional correlative study<br>Genetic: polymorphism analysis<br>* Correlative study<br>Other: pharmacogenomic studies<br>* Correlative study<br>* Other names: Pharmacogenomic Study;Genetic: genetic linkage analysis<br>* Correlative study<br>* Other names: linkage analysis;Drug: docetaxel<br>* Given IV<br>* Other names: TXT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Determined using RECIST. Estimated using the Kaplan-Meier method. Log-rank tests will be used to test for differences and Cox proportional hazards regression modeling will be used to adjust for patient demographics and characteristics such as smoking status at baseline (actively/non-actively smoking). Progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood | 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. Pre-specified that data is only presented for the subgroups Low Cyclin D1 and High Cyclin D1. | 2 years | 
| Median Survival Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood |  | 2 years |