Carboplatin, Gemcitabine, and Thalidomide in Patients Undergoing Surgery for Stage II or III Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as carboplatin and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Thalidomide may stop the growth of tumor cells by blocking blood flow to the tumor. Giving carboplatin and gemcitabine together with thalidomide before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving carboplatin and gemcitabine together with thalidomide works in treating patients who are undergoing surgery for stage II or stage III non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the complete and partial response rates in patients with stage II or IIIA non-small cell lung cancer treated with neoadjuvant carboplatin, gemcitabine hydrochloride, and thalidomide. Secondary Determine, preliminarily, the mechanism of action and activity of thalidomide against lung cancer. Determine the 1-year and 2-year survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. Determine the operative mortality of patients treated with this regimen. OUTLINE: This is a pilot study. Patients receive carboplatin intravenously (IV) over 30 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, and oral thalidomide once daily on days 1-21. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Within 2-6 weeks after the completion of chemotherapy, patients with resectable tumors undergo surgical resection. After completion of study treatment, patients are followed every 3 months for 2 years.

Official Title
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Phase II Trial of Neoadjuvant Therapy With Carboplatin and Gemcitabine With Thalidomide in Patients With Stage II and IIIA Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: gemcitabine hydrochloride
* Drug: thalidomide
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including any of the following histologic subtypes: Squamous cell carcinoma Adenocarcinoma Large cell undifferentiated carcinoma Stage II or IIIA disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral Computerized Axial Tomography (CT) scan No tumor involving the superior sulcus (e.g., Pancoast tumor) Karnofsky performance status 70-100% Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Creatinine ≤ 2 mg/dL Bilirubin < 2 mg/dL Aspartate aminotransferase (AST) < 3 times upper limit of normal Exclusion Criteria: Pregnant or nursing No nursing during and for ≥ 4 weeks after completion of study treatment Positive pregnancy test Fertile female patients must use 2 effective methods of contraception 4 weeks before, during, and for 4 weeks after completion of study treatment Fertile male patients must use effective barrier contraception during and for 4 weeks after completion of study treatment Blood, sperm, or ova donation during study treatment Post obstructive pneumonia Other serious infection or medical illness that would preclude study participation Other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other malignancy that is unlikely to affect survival for the next 3 years Less than 5 years since prior resection of lung disease Prior systemic chemotherapy or radiotherapy for non-small cell lung cancer (NSCLC) Other concurrent chemotherapy or radiotherapy Concurrent hormonal therapy or immunotherapy Other concurrent anticancer therapy Other concurrent investigational agents Concurrent participation in another clinical study

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Chemotherapy treatment (carboplatin, gemcitabine and thalidomide) every 21 days for 3 courses. | Drug: carboplatin<br>* Day 1 of Cycles 1, 2 and 3 - intravenously (IV) 30 minutes (Area Under the Curve = 5.5)<br>* Other names: PARAPLATIN;Drug: gemcitabine hydrochloride<br>* Days 1 and 8 of Cycles 1, 2 and 3 - 30 minute IV, 1000 mg/m2.<br>* Other names: Gemzar;Drug: thalidomide<br>* Oral administration: Cycle 1 - Day 1 50 mg, Day 2 100 mg, Day 3 150 mg, Day 4 and continuing until end of study treatment 200 mg.<br>* Other names: Thalidomid;Procedure: conventional surgery<br>* Resection - between 2 and 6 weeks following last dose of chemotherapy.<br>* Other names: Resection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Reporting Clinical Response | Objective clinical response measuring using tumor assessments: Complete Response (CR) = disappearance of all target and non-target lesions and normalization of tumor marker level, if applicable. Pathological Complete Response (PCR) = No viable tumor cells in specimen determined by light microscopy. Partial Response (PR) = at least 30% decrease in the sum of longest diameter of target lesions from baseline. Progressive Disease (PD) = at least 20% increase in the sum of longest diameters of target lesions from baseline or new lesions. Stable Disease (SD) = Neither PR or PD. | At end of 3 -21 day cycles of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Disease-free at 1 Year | Calculated from date of enrollment to date of recurrence or death, whichever came first | 1 year | 
| Number of Patients Disease-free at 2 Years | Calculated from date of enrollment to date of recurrence or death, whichever came first | 2 Years | 
| Number of Patients Alive at 1 Year (Survival) | Participants who were alive at one year from date of enrollment . | 12 Months | 
| Number of Patients Alive at 2 Years (Survival) | Participants who were alive at 2 years from date of enrollment. | 24 Months | 
| Number of Patients Alive at 56 Months (End of Study) | Patients alive from date of enrollment to date of death or censored at date of last contact (Overall Survival). | Up to 56 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the lung, squamous cell lung cancer, large cell lung cancer, stage II non-small cell lung cancer, stage IIIA non-small cell lung cancer