S0526: Pemetrexed Disodium in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well pemetrexed disodium works in treating patients with stage III or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Assess overall survival of patients with selected stage IIIB or IV bronchoalveolar carcinoma treated with pemetrexed disodium. Secondary Evaluate the progression-free survival of patients treated with this drug. Evaluate the response rate (confirmed and unconfirmed, partial and complete) in the subset of patients with measurable disease treated with this drug using standard RECIST criteria and computer assisted image analysis. Evaluate frequency and severity of toxicities in patients treated with this drug. Perform molecular correlative studies on patient tissue to investigate potential predictors of efficacy. (This will not be completed as this study was closed due to poor accrual.) OUTLINE: Patients are stratified according to prior treatment with gefitinib or erlotinib (yes vs no). Patients receive pemetrexed disodium intravenous (IV) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 3 years. PROJECTED ACCRUAL: A total of 99 patients will be accrued for this study.

Official Title
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Phase II Trial of Pemetrexed in Patients With Selected Stage IIIB and IV Bronchioloalveolar Carcinoma (BAC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: pemetrexed


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed bronchoalveolar carcinoma (BAC) or BAC variants such as adenocarcinoma with BAC features or BAC with invasive adenocarcinoma Cytology specimens, such as bronchial brushings, washings, or fine needle aspiration specimens alone are not acceptable for diagnosis Stage IV disease OR selected stage IIIB (T4 [secondary to malignant pleural effusion only], any N, M0) disease Incompletely resected or unresectable disease Pleural effusions, ascites, or laboratory parameters cannot be only evidence of disease Measurable disease or nonmeasurable disease documented by CT scan No known brain metastases PATIENT CHARACTERISTICS: Bilirubin ≤ 1.5 times upper limit of normal (ULN) SGOT and SGPT ≤ 2.5 times ULN ( ≤ 5 times ULN if due to liver metastases) Alkaline phosphatase ≤ 2.5 times ULN ( ≤ 5 times ULN if due to bone metastases) Creatinine clearance ≥ 45 mL/min OR creatinine ≤ 1.5 times ULN Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 75,000/mm³ Zubrod 0-2 No history of allergic reaction to compounds of similar chemical or biological composition as pemetrexed disodium Must provide smoking history No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission Not pregnant or nursing Fertile patients must use effective contraception Able to swallow pills PRIOR CONCURRENT THERAPY: No more than 2 prior systemic therapies (including epidermal growth factor receptor inhibitor) At least 28 days since prior systemic therapy Patients treated with prior erlotinib or gefitinib must have shown progression since treatment No prior pemetrexed disodium At least 28 days since prior radiotherapy and recovered Must have measurable or nonmeasurable disease outside previously irradiated area or a new lesion within previously irradiated area At least 14 days since prior palliative radiotherapy and recovered At least 28 days since prior thoracic or major surgery and recovered No concurrent surgery No other concurrent therapy (hormonal, biologic or radiotherapy) for this disease No concurrent antiretroviral therapy Patients should discontinue non-steroidal anti-inflammatory drugs (NSAIDs) with longer half lives (etodolac, ketordac, sulindac, naproxen, naproxen sodium, oxaprozin, nabumetone, diflunisal, salsalate, celecoxib, rofecoxib, valdecoxib, meloxicam, piroxicam) at least 5 days before and for 2 days following pemetrexed treatment

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: Pemetrexed<br>pemetrexed | Drug: pemetrexed<br>* Pemetrexed 500 mg/m^2 intravenous (IV) over 10 min every 21 days until any of the following criteria is met: (1) Progression of disease or symptomatic deterioration; (2) Unacceptable toxicity; (3) Treatment delay ≥ 3 weeks, for any reason; (4) The patient may withdraw from the study at any time for any reason; (5) Physician's discretion.<br>* Other names: Alimta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Measured from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. | 0 - 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression is defined as any one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline; Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided); Appearance of any new lesion/site; Death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is defined as globabl deterioration of health status requiring discontinuation of treatment without objective evidence of progression. Progression-free survival is measured from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact. | 0 - 3 years | 
| Response (Confirmed and Unconfirmed, Complete and Partial) | Complete response (CR) is complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other abnormal lab values. Partial Response (PR) is greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. Confirmation of CR or PR means a repeat scan at least 4 weeks apart documented before progression or symptomatic deterioration. | Assessed at weeks 7 and 13 while on treatment. After off treatment prior to disease progression, disease assessment takes place every 3 months for a maximum of 3 years. | 
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. | Patients were assessed for adverse events 4 weeks after starting treatment. Assessments for adverse events continued after every cycle of treatment (every 3 weeks) for the duration of protocol treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bronchoalveolar cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer