Pemetrexed Disodium Plus Gemcitabine in Treating Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug and giving the drugs in different ways may kill more tumor cells. PURPOSE: Randomized phase II trial to compare the effectiveness of three different regimens of pemetrexed disodium plus gemcitabine in treating patients who have locally advanced or metastatic non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Compare the tumor response rates in patients with locally advanced or metastatic non-small cell lung cancer treated with 3 different schedules of pemetrexed disodium and gemcitabine. Compare the duration of response, time to progressive disease, time to treatment failure, and survival time in patients treated with these regimens. Compare the quantitative and qualitative toxic effects of these regimens in these patients. OUTLINE: This is a randomized, open-label study. Patients are stratified according to stage of disease (IIIB vs IV) and ECOG performance status (0 vs 1). Patients are randomized to one of three treatment arms. Arm I: Patients receive pemetrexed disodium IV over 10 minutes on day 1 followed by gemcitabine IV over 30 minutes on days 1 and 8. Arm II: Patients receive gemcitabine IV over 30 minutes on days 1 and 8 followed by pemetrexed disodium IV over 10 minutes on day 1. Arm III: Patients receive gemcitabine IV over 30 minutes on day 1 and pemetrexed disodium IV over 10 minutes followed by gemcitabine IV over 30 minutes on day 8. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive up to 6 additional courses of therapy. Patients are followed every 2 months for 1 year and then every 6 months for 4 years. PROJECTED ACCRUAL: A total of 180 patients (60 per treatment arm) will be accrued for this study within 20 months.

Official Title
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A Phase II Clinical Trial Evaluating Three Schedules Of ALIMTA Plus Gemcitabine As Frontline Chemotherapy For Patients With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer Stage IIIB disease that is ineligible for combined modality therapy OR Stage IV disease Measurable disease No clinically detectable (by physical exam) third-space fluid collection (e.g., ascites or pleural effusions) that cannot be controlled by drainage or other procedures No brain metastases (even if treated) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: At least 12 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) AST and ALT no greater than 3 times ULN (5 times ULN if liver metastases present) Alkaline phosphatase no greater than 3 times ULN (5 times ULN if liver metastases present) Renal: Creatinine clearance at least 45 mL/min Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to take folic acid or cyanocobalamin (vitamin B12) supplementation No uncontrolled infection No concurrent chronic debilitating disease No weight loss of 10% or more within the past 6 weeks No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinoma PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic or genetic therapy for lung cancer No concurrent immunomodulating agents Chemotherapy: No prior chemotherapy for lung cancer Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior radiotherapy to a different site and recovered No prior radiotherapy to 25% or more of bone marrow No prior radiotherapy to whole pelvis No prior radiotherapy for primary disease No concurrent radiotherapy Surgery: More than 4 weeks since prior major surgery Other: No aspirin or nonsteroidal anti-inflammatory agents 2 days before, during, and for 2 days after pemetrexed disodium administration (5 days for long-acting agents such as piroxicam, naproxen, diflunisal, or nabumetone) No other concurrent cytostatic or cytotoxic therapy

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I: pemetrexed + gemcitabine<br>Patients receive pemetrexed disodium IV over 10 minutes on day 1 followed by gemcitabine IV over 30 minutes on days 1 and 8. | Drug: gemcitabine hydrochloride<br> <br> Drug: pemetrexed disodium<br> <br> |
| Experimental: Arm II: pemetrexed + gemcitabine<br>Patients receive gemcitabine IV over 30 minutes on days 1 and 8 followed by pemetrexed disodium IV over 10 minutes on day 1. | Drug: gemcitabine hydrochloride<br> <br> Drug: pemetrexed disodium<br> <br> |
| Experimental: Arm III: pemetrexed + gemcitabine<br>Patients receive gemcitabine IV over 30 minutes on day 1 and pemetrexed disodium IV over 10 minutes followed by gemcitabine IV over 30 minutes on day 8. | Drug: gemcitabine hydrochloride<br> <br> Drug: pemetrexed disodium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tumor response rate |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of response |  | Up to 4 years | 
| time to treatment failure |  | Up to 4 years | 
| survival |  | Up to 4 years | 
| time to disease progression |  | Up to 4 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