Pemetrexed Disodium and Gemcitabine 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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RATIONALE: Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving pemetrexed disodium together with gemcitabine may kill more tumor cells. PURPOSE: This randomized phase II trial is studying two different schedules of pemetrexed disodium and gemcitabine to compare how well they work in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Compare response rates in patients with stage IIIB or IV non-small cell lung cancer treated with two different treatment schedules of pemetrexed disodium and gemcitabine hydrochloride. Secondary Compare time-to-event efficacy variables in patients treated with these regimens. Compare progression-free and overall survival of patients treated with these regimens. Determine the overall toxicity of these regimens in these patients. OUTLINE: This is a multicenter, open-label, randomized study. Patients are stratified according to disease stage (IIIB vs IV) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV over 30 minutes on day 1. Treatment repeats every 14 days for up to 9 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for up to 2 years. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

Official Title
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A Randomized Phase II Study of ALIMTA® (Pemetrexed) and GEMZAR® (Gemcitabine) Every 14 Days Versus Pemetrexed and Gemcitabine Every 21 Days in Advanced Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: gemcitabine HCL
* Drug: pemetrexed disodium
* Drug: gemcitabine HCL


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 IIIB (with controlled pleural effusion) OR stage IV disease At least 1 measurable lesion whose longest diameter is ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan No medically significant third-space fluid collection (e.g., ascites or pleural effusions) that cannot be controlled by drainage or other procedures No documented brain metastases unless all of the following criteria are met: Successful local therapy has been completed At least 2 weeks since prior corticosteroids Brain imaging required for symptomatic patients only (to rule out brain metastases) Concurrent enrollment in clinical trial MCCRC-RC0527 required PATIENT CHARACTERISTICS: Life expectancy ≥ 12 weeks ECOG performance status 0-1 Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9.0 g/dL Bilirubin ≤ 1.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 3 times ULN AST and ALT ≤ 3 times ULN (5 times ULN for liver involvement) Creatinine clearance ≥ 45 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to take folic acid, cyanocobalamin (vitamin B12) supplementation, or dexamethasone and corticosteroids Able to interrupt intake of aspirin and nonsteroidal anti-inflammatory agents for a total of 5 days No severe and/or uncontrolled medical conditions, including any of the following: Hypertension, labile hypertension, or history of poor compliance with antihypertensive medication Angina pectoris Congestive heart failure within the past 3 months, unless ejection fraction > 40% Myocardial infarction within the past 6 months Cardiac arrhythmia Diabetes Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung New York Heart Association class III or IV heart disease Clinically significant infection No other serious medical condition or illness that would preclude study participation No peripheral neuropathy ≥ grade 2 No other malignancy within the past 5 years except nonmelanomatous skin cancer, carcinoma in situ of the cervix, or low-grade (Gleason score ≤ 6) localized prostate cancer No significant weight loss (≥ 10%) within the past 6 weeks No investigator site personnel directly affiliated with the study, or immediate family (i.e., spouse, parent, child, or sibling, whether biological or legally adopted) No employees of Eli Lilly (i.e., employees, temporary contract workers, or designees responsible for conducting the study) Immediate family of Eli Lilly employees may participate in Eli Lilly-sponsored clinical trials, but are not permitted to participate at an Eli Lilly facility PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 2 weeks since prior corticosteroids At least 4 weeks since prior radiation therapy involving > 25% of the bone marrow and recovered At least 30 days since prior investigational therapy No prior radiation therapy to the whole pelvis No prior systemic chemotherapy for advanced non-small cell lung cancer No prior pemetrexed disodium and/or gemcitabine hydrochloride No prior or concurrent sorafenib tosylate and/or temsirolimus No concurrent Hypericum perforatum (St. John's wort) No other concurrent antitumor therapy No concurrent agents that stimulate thrombopoiesis Concurrent palliative radiation therapy allowed Concurrent corticosteroids allowed for adrenal insufficiency or severe nausea and vomiting

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gemzar x2<br>Treat subjects with 2 dosings/cycle of Gemzar x6 cycles. | Drug: gemcitabine HCL<br>* 1250 mg/m^2 administered through 250 cc NS (normal saline) IV (intravenous) infusion over 30 minutes at days 1 & 8 of each cycle (21 days) x6 cycles.<br>* Other names: GEMZAR;Drug: pemetrexed disodium<br>* 500 mg/m^2 administered through 100 mL NS IV infusion over 10 minutes at day 1 of each cycle.<br>* Other names: ALIMTA;|
| Experimental: Gemzar x1<br>Treat subjects with 1 dosing/cycle of Gemzar x9 cycles. | Drug: pemetrexed disodium<br>* 500 mg/m^2 administered through 100 mL NS IV infusion over 10 minutes at day 1 of each cycle.<br>* Other names: ALIMTA;Drug: gemcitabine HCL<br>* 1500 mg/m^2 administered through 250 cc NS IV infusion over 30 minutes at days 1 of each cycle (14 days) x9 cycles.<br>* Other names: GEMZAR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Confirmed Responses | Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 6 weeks apart. > > Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions. | Two consecutive evaluations at least 6 weeks apart (up to 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival was defined as the number of months from registration to the date of disease progression or death, with patients who are alive and progression free being censored on the date of their last evaluation. | Time from registration to progression or death (up to 2 years) | 
| Overall Survival | Overall survival time was defined as the number of months from registration to the date of death or last follow-up | Death or last follow-up (up to 2 years) | 
| Adverse Event | Number of patients that experienced adverse events (grade 4 or more) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0 | Gemzar x2 Arm every 21 days, Gemzar x1 Arm every 14 days (up to 2 years) | 

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