Positron Emission Tomography in Predicting Response in Patients Who Are Undergoing Treatment With Pemetrexed Disodium and Cisplatin With or Without Surgery for Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Diagnostic procedures, such as positron emission tomography (PET), (done before, during, and after chemotherapy) may help doctors predict a patient's response to treatment and help plan the best treatment. Drugs used in chemotherapy, such as pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well PET works in predicting response in patients who are undergoing treatment with pemetrexed disodium and cisplatin with or without surgery for stage I, stage II, or stage III non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the effectiveness of fludeoxyglucose F 18 positron emission tomography in predicting radiological and pathological response in patients treated with pemetrexed disodium and cisplatin with or without surgery for stage IB-IIIB non-small cell lung cancer (NSCLC). Secondary Determine the safety of cisplatin and pemetrexed disodium in these patients. Determine the radiographic response rate, duration of response, and time to progression in patients treated with cisplatin and pemetrexed disodium. OUTLINE: This is a multicenter study. Fludeoxyglucose F 18 (18FDG) positron emission tomography (PET) imaging: All patients undergo positron emission tomography (PET) imaging of the head, neck, thorax, abdomen, and pelvis. Patients receive fludeoxyglucose F 18 (^18FDG) IV followed by 45 minutes of rest. PET imaging is done over 1 hour and 8 minutes. Patients undergo PET imaging at three points during the study: 4 weeks prior to treatment, after the first cycle of treatment, and after 3 courses of chemotherapy. Some patients then undergo surgical resection of the tumor. Chemotherapy: Patients receive cisplatin IV over 30 minutes and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.

Official Title
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Early Positron Emission Tomography as a Predictor of Response in Neoadjuvant Chemotherapy for Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: pemetrexed disodium
* Procedure: adjuvant therapy
* Procedure: therapeutic conventional surgery
* Radiation: fludeoxyglucose F 18


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) Stage IB, II, IIIA, or IIIB (T4, N0-1) disease Staging must have been performed 4 weeks prior to study entry with a CT scan of chest, upper abdomen, and fludeoxyglucose F 18 (^18FDG) positron emission tomography (PET) scan Mediastinal evaluation and staging based on combination of CT scan and FDG-PET results If N1 or N2 nodes are found by FDG-PET or CT scan, metastases must be ruled out by brain MRI Measurable and resectable disease T4 lesions must be resectable Eligible for curative surgery No malignant pleural effusion PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,250/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 3.0 times ULN Renal Creatinine clearance ≥ 45 mL/min Pulmonary Adequate pulmonary reserve to undergo surgery Predicted FEV_1 > 0.8 L after resection Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study treatment Able to take corticosteroids Able to take folic acid or vitamin B_12 supplements No other malignancy within the past 5 years except nonmelanoma skin cancer or noninvasive cervical cancer No concurrent serious or uncontrolled disorder that would preclude study participation No type I diabetes mellitus Type II diabetes mellitus allowed if glucose is 80-150 mg/dL PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy No concurrent prophylactic filgrastim (G-CSF) No concurrent thrombopoiesis-stimulating agents Chemotherapy At least 5 years since prior chemotherapy Endocrine therapy No concurrent anticancer hormonal therapy Radiotherapy No prior radiotherapy to the chest No concurrent curative or palliative radiotherapy Surgery Not specified Other At least 30 days since prior non-FDA-approved or investigational agents At least 5 days since prior aspirin or other nonsteroidal anti-inflammatory agents (8 days for long-acting agents [e.g., piroxicam]) No other concurrent anticancer therapy No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Neoadjuvant therapy, PET scan and surgery<br> | Drug: cisplatin<br> <br> Drug: pemetrexed disodium<br> <br> Procedure: adjuvant therapy<br> <br> Procedure: therapeutic conventional surgery<br> <br> Radiation: fludeoxyglucose F 18<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positron Emission Tomography as a Predictor of Response Measured by the Decrease in Standard Uptake Variable (SUV) After 1 Course of Therapy | Number of Participants with Decrease in Standard Uptake Variable (SUV) After 1 Course of Therapy | Between days 18 and 22 prior to second chemotherapy infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Neoadjuvant Chemotherapy | The number of patients that experienced a grade 3 or higher adverse event. | Up to 4 weeks after last dose of chemotherapy | 
| Efficacy of Neoadjuvant Chemotherapy as Measured by Radiologic Response Rate | The number of patients that had either a CR, PR or SD after the completion of chemotherapy. 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; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. | Up to 4 weeks after last dose of chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I non-small cell lung cancer, stage II non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer