MILES-4: Study Comparing Gemcitabine and Pemetrexed, With or Without Cisplatin, in Patients With Nonsquamous Lung Cancer

Study Overview
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Brief Summary
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The purposes of this study are to test whether the addition of cisplatin to single agent chemotherapy (either gemcitabine or pemetrexed) prolongs survival in elderly patients with non squamous non small cell lung cancer (NSCLC), and to test whether pemetrexed prolongs survival as compared to gemcitabine in elderly patients with non squamous NSCLC.

Official Title
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A Factorial Study Comparing Pemetrexed With Gemcitabine and Testing the Efficacy of the Addition of Cisplatin in Elderly Patients With Non Squamous Advanced, Metastatic or Recurrent NSCLC.

Conditions
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Non-small Cell Lung Cancer Metastatic, Non-small Cell Lung Cancer Stage IIIB

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Pemetrexed
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of cytologically or histologically confirmed non-small cell lung cancer. Non squamous tumor type (including those with a non-specified tumor type). Metastatic (stage IV, both M1A or M1B) or locally advanced (stage IIIB, with metastasis to supraclavicular nodes) according to TNM VII edition. Both patients at first diagnosis or those with disease recurrence after former surgery are eligible. At least one target or non-target lesion according to RECIST revised version 1.1. Male or female > or = 70 years of age. ECOG PS 0 or 1. Life expectancy > 3 months. Neutrophils > or = 1500 mm3, platelets > or = 100000 mm3, and haemoglobin > or = 9 g/dL. Bilirubin level either normal or < 1.5 x ULN. AST (SGOT) and ALT (SGPT) < or = 2.5 x ULN (< or = 5 x ULN if liver metastasis are present). Serum creatinine < 1.5 x ULN. Signed written informed consent. Exclusion Criteria: Prior chemotherapy or therapy with systemic anti-neoplastic therapy for advanced disease. Prior surgery and/or localised irradiation is permitted. Prior adjuvant chemotherapy is permitted if it did not contain gemcitabine and pemetrexed and if at least 6 months elapsed from the end of adjuvant chemotherapy. Any unstable systemic disease (including active infections, significant cardiovascular disease or myocardial infarction within the previous year, any significant hepatic, renal or metabolic disease), metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of study medications or render the patient at high risk from treatment complications. Any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA). Patients with symptomatic brain metastasis or spinal cord compression that has not yet been treated with surgery and/or radiation; patients with CNS metastases or spinal cord compression previously treated with surgery and/or radiation are eligible if they are asymptomatic and do not require steroids (anti-seizure medications are allowed). Known or suspected hypersensitivity to any of the study drugs

Ages Eligible for Study
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Minimum Age: 70 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A: Gemcitabine<br>Single agent gemcitabine dose 1200 mg/m2 days 1 and 8, every 3 weeks | Drug: Gemcitabine<br> <br> |
| Experimental: B: Gemcitabine + Cisplatin<br>Gemcitabine dose 1000 mg/m2 days 1 and 8, every 3 weeks | Drug: Gemcitabine<br> <br> Drug: Cisplatin<br>* 60 mg/m2 day 1 every 3 weeks<br>|
| Active Comparator: C: Pemetrexed<br> | Drug: Pemetrexed<br>* 500 mg/m2 day 1 every 3 weeks<br>|
| Experimental: D: Pemetrexed + Cisplatin<br> | Drug: Pemetrexed<br>* 500 mg/m2 day 1 every 3 weeks<br>Drug: Cisplatin<br>* 60 mg/m2 day 1 every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | factorial design with two comparisons: single agent chemotherapy versus chemotherapy plus cisplatin (Arms A+C versus Arms B + D), and gemcitabine versus pemetrexed (Arms A+B versus Arms C+D) | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| worst grade toxicity per patient | according to Common Toxicity Criteria for Adverse Events v. 4.03 | evaluated at end of each 3 week cycle of chemotherapy up to 18 weeks | 
| progression free survival |  | 6 months | 
| changes in quality of life |  | baseline and up to 18 weeks | 
| objective response |  | after 9 and 18 weeks of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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elderly, chemotherapy