Pemetrexed Disodium and Carboplatin in Treating Patients With Extensive-Stage 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 and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving pemetrexed disodium together with carboplatin works in treating patients with extensive-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the complete and partial response rates in patients with previously untreated, extensive-stage small cell lung cancer treated with pemetrexed disodium and carboplatin. Secondary Determine the toxicity of this regimen in these patients. Determine, preliminarily, the survival of patients treated with this regimen. Determine, preliminarily, the response rate in patients 70 years and older treated with this regimen. Determine, preliminarily, the toxicity of this regimen in patients 70 years and older. OUTLINE: This is a multicenter study. Patients are stratified according to age (< 70 years vs ≥ 70 years). Patients receive pemetrexed disodium IV over 10 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who develop progressive disease in the CNS only may receive whole-brain radiotherapy and then continue chemotherapy after completion of whole-brain radiotherapy for up to 6 courses. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 4 years. PROJECTED ACCRUAL: Approximately 77 patients at least 46 who are < 70 years of age and at least 24 who are ≥ 70 years of age) will be accrued for this study within 20-26 months.

Official Title
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Phase II Trial of Pemetrexed Disodium and Carboplatin in Previously Untreated Extensive Stage Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: pemetrexed disodium
* Radiation: radiation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell lung cancer Previously untreated disease No mixed histology Extensive-stage disease Clinically significant effusions (e.g., symptomatic pleural effusion) must be drained prior to treatment Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan No symptomatic, untreated, or uncontrolled CNS metastases CNS metastases previously treated with whole-brain radiotherapy allowed PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 12 weeks Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL Hepatic Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR Direct bilirubin normal ALT and AST ≤ 3 times ULN (5 times ULN if there is liver involvement) Renal Creatinine clearance ≥ 45 mL/min Cardiovascular No angina pectoris No congestive heart failure within the past 3 months, unless ejection fraction > 40% No cardiac arrhythmia No myocardial infarction within the past 3 months No hypertension, including labile hypertension Pulmonary No interstitial pneumonia No extensive and symptomatic interstitial fibrosis of the lung Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of poor compliance with antihypertensive medication Able to take folic acid, cyanocobalamin (vitamin B_12) supplementation, or dexamethasone No uncontrolled diabetes No serious condition that would preclude study participation No clinically significant infection No significant traumatic injury No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer Low-grade (Gleason score ≤ 6), localized prostate cancer allowed even if diagnosed < 5 years prior to study entry No seizure disorder No other severe and/or uncontrolled medical condition PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent immunotherapy No concurrent immunomodulating agents Chemotherapy No other concurrent chemotherapy Endocrine therapy No concurrent hormonal therapy Radiotherapy See Disease Characteristics Prior palliative radiotherapy allowed No prior palliative radiotherapy to the chest except for ≤ 3 fractions for superior vena cava syndrome No concurrent radiotherapy Surgery More than 4 weeks since prior major surgery* (i.e., laparotomy) or open biopsy More than 2 weeks since prior minor surgery* NOTE: *Insertion of a vascular access device is not considered major or minor surgery Other More than 4 weeks since prior investigational therapy No concurrent Hypericum perforatum (St. John's wort) No concurrent inducers or inhibitors of CYP3A4 No concurrent medications that are metabolized by CYP3A4 No aspirin dose ≥ 1.3 grams per day for ≥ 10 days prior to and after study treatment No other concurrent cytostatic or cytotoxic agents

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 + carboplatin + radiation<br>Patients receive pemetrexed disodium IV over 10 minutes and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who develop progressive disease in the CNS only may receive whole-brain radiotherapy and then continue chemotherapy after completion of whole-brain radiotherapy for up to 6 courses. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for 4 years. | Drug: carboplatin<br> <br> Drug: pemetrexed disodium<br> <br> Radiation: radiation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of confirmed-tumor response |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extensive stage small cell lung cancer