Dose-Dense Induction/Neoadjuvant Chemotherapy in Locally Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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Dose-dense chemotherapy is a chemotherapy treatment plan in which drugs are given with less time between treatments than in standard chemotherapy. The two chemotherapy drugs used in this study, docetaxel and cisplatin, are approved for the treatment of lung cancer when given every 21 days. This study is exploring the response to chemotherapy when these drugs are given every 14 days. In addition, genetic tests will be performed on pre-treatment specimens to identify signatures that may predict chemotherapy sensitivity or resistance.

Detailed Description
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All patients will receive induction chemotherapy with cisplatin and docetaxel. Pegfilgrastim will be administered approximately 24 hours following the end of the day 1 chemotherapy infusion. Cycles will be repeated every 2 weeks for 3 cycles. Patients deemed to be resectable will undergo surgical resection followed by postoperative thoracic radiotherapy. Patients deemed inoperable will additionally receive concurrent chemoradiotherapy. Response, using radiographic and/or pathologic means, will identify two cohorts; responders and nonresponders.Gene expression profiling will then be performed on pre-treatment specimens to identify signatures that predict for chemotherapy sensitivity or resistance. The target enrollment is 45 patients.

Official Title
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Dose-Dense Induction/Neoadjuvant Chemotherapy in the Treatment of Patients With Locally Advanced Non-Small Cell Lung Cancer With Additional Genomic Analyses to Identify Signatures Predictive of Chemotherapy Response.

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: Docetaxel
* Drug: Pegfilgrastim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with documented stage III NSCLC (IIIA or IIIB, without malignant pleural/pericardial effusion) are eligible for enrollment if they are considered appropriate for treatment with chemotherapy, radiation, or surgery; IIIA: T1-3 N2 M0, T3 N1 M0 IIIB: T4 N0-2 M0, T 1-4 N3 M0 Measurable or evaluable disease Previously untreated with chemotherapy or radiotherapy for lung cancer; No brain metastases; No prior XRT Performance status 0-2 ≥18 years of age Informed Consent Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L Bilirubin ≤ 1.5 x upper limit of normal for the institution (ULN) SGOT and SGPT ≤ 2.5 x ULN for the institution Creatinine ≤ 1.6 mg/dL Hemoglobin ≥ 8.0 g/dL Peripheral neuropathy ≤ grade 1 Exclusion Criteria: Known sensitivity to E. coli derived products (e.g. Filgrastim, HUMULIN® insulin, L-asparaginase, HUMATROPE® Growth Hormone, INTRON® A); Use of IV systemic antibiotics within 72 hours prior to chemotherapy; Known HIV infection Lithium or cytokines within 2 weeks prior of entry Additional concurrent investigational drugs History of myelodysplastic syndrome Pregnant, nursing or having unprotected sex Not available for follow-up assessment Unable to comply with protocol procedures Illnesses that may compromise ability to give informed consent. Patients with a history of severe hypersensitivity reaction to Taxotere® or other drugs formulated with polysorbate 80.

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: Induction Chemotherapy<br>Cisplatin 75mg/m2 IV days 1, 15, 29; Docetaxel 75mg/m2 IV days 1, 15, 29; and Pegfilgrastim 6mg SC day 2, 16, 30 | Drug: cisplatin<br> <br> * Other names: Platinol;Drug: Docetaxel<br> <br> * Other names: Taxotere;Drug: Pegfilgrastim<br> <br> * Other names: Neulasta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Induction Response | Response will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Response is defined as the number patients with a Complete Response (CR), disappearance of all target lesions, or a Partial Response (PR), at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. | Between 2 and 3 weeks after induction | 
| Differential Gene Expression Between Responsive and Resistant Tumor Treated With Dose-dense Therapy |  | at the end of the study, estimated 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Grade III/IV Hematologic Adverse Events |  | During induction chemotherapy, approximately 6 weeks | 
| Number of Grade III/IV Non-hematologic Adverse Events |  | During induction chemotherapy, approximately 6 weeks | 
| Number of Patients Who Were Able to Maintain Hemoglobin Between 11-13 g/dL During Induction |  | During induction, approximately 6 weeks | 
| Overall Survival |  | Approximately 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dose-Dense Chemotherapy