Docetaxel and Cisplatin With or Without Dimesna 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: Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as dimesna, may help prevent or decrease the side effects (such as nerve, kidney, and inner ear damage) caused by chemotherapy. PURPOSE: This randomized phase II trial is studying giving docetaxel and cisplatin together with dimesna to see how well it works compared to giving docetaxel and cisplatin alone in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Compare the incidence and severity of peripheral neuropathy in patients with stage IIIB or IV non-small cell lung cancer treated with docetaxel and cisplatin with or without dimesna. Compare the feasibility of these regimens, in terms of febrile neutropenia and treatment delays, in these patients. Compare the objective response rate in patients treated with these regimens. Secondary Compare the survival and failure-free survival of patients treated with these regimens. Compare the toxicity profile of these regimens in these patients. Compare the incidence and severity of cisplatin-induced nephrotoxicity in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I*: Patients receive docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 and pegfilgrastim subcutaneously (SC) on day 2. Arm II*: Patients receive docetaxel, cisplatin, and pegfilgrastim as in arm I and dimesna IV over 30 minutes on day 1. NOTE: *In both arms, darbepoetin alfa is administered SC on day 1 of each course for hemoglobin ≤ 11 g/dL. In both arms, treatment repeats every 2 weeks for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

Official Title
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A Phase II Randomized Study Of Dose-Dense Docetaxel And Cisplatin Every Two Weeks With Pegfilgrastim And Darbepoetin Alfa With And Without The Chemoprotector BNP7787 In Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Anemia, Drug/Agent Toxicity by Tissue/Organ, Lung Cancer, Neutropenia

Intervention / Treatment
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* Biological: darbepoetin alfa
* Biological: pegfilgrastim
* Drug: cisplatin
* Drug: docetaxel
* Drug: BNP7787


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed* non-small cell lung cancer of 1 of the following subtypes: Squamous carcinoma Basaloid carcinoma Adenocarcinoma Bronchoalveolar carcinoma Adenosquamous carcinoma Large cell carcinoma Large cell neuroendocrine carcinoma Giant cell carcinoma Sarcomatoid carcinoma Non-small cell carcinoma not otherwise specified NOTE: *Histologic or cytologic confirmation of recurrence is required for patients who have undergone prior complete resection Stage IIIB disease due to malignant pleural effusion OR stage IV disease Measurable disease At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan The following are considered nonmeasurable disease: Bone lesions Brain metastases or leptomeningeal disease Ascites Pleural/pericardial effusion Abdominal masses not confirmed and followed by imaging techniques Cystic lesions Tumor lesions situated in a previously irradiated area Brain metastases are allowed provided patient is neurologically stable and off steroids PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic Granulocyte count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 1.5 mg/dL AST ≤ 1.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Renal Creatinine ≤ ULN Other Not pregnant or nursing Fertile patients must use effective contraception No grade 2 or greater neuropathy PRIOR CONCURRENT THERAPY: Biologic therapy No other concurrent growth factors Chemotherapy No prior chemotherapy No other concurrent chemotherapy Endocrine therapy See Disease Characteristics No concurrent hormonal therapy except steroids administered for adrenal failure, hormones for non-cancer-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic Radiotherapy See Disease Characteristics Prior radiotherapy allowed for brain metastases only No concurrent palliative radiotherapy Surgery See Disease Characteristics

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: Chemotherapy without BNP7787<br>Chemotherapy with dose-dense docetaxel and cisplatin with pegfilgrastim and darbepoetin for pts with NSCLC | Biological: darbepoetin alfa<br>* 200 mcg sub Q on day 1 of each cycle if HgB < or = 11 g/dL<br>Biological: pegfilgrastim<br>* 6 mg sub Q day 2 of each cycle<br>Drug: cisplatin<br>* 75 mg/sq m IV over 1 hr Day 1 of each cycle<br>Drug: docetaxel<br>* 75 mg/sq m IV over 1 hr Day 1 of each cycle<br>|
| Experimental: Chemotherapy + BNP7787<br>Chemotherapy with dose-dense docetaxel and cisplastin with pegfilgrastim and darbepoetin with the addition of BNP7787 | Biological: darbepoetin alfa<br>* 200 mcg sub Q on day 1 of each cycle if HgB < or = 11 g/dL<br>Biological: pegfilgrastim<br>* 6 mg sub Q day 2 of each cycle<br>Drug: cisplatin<br>* 75 mg/sq m IV over 1 hr Day 1 of each cycle<br>Drug: docetaxel<br>* 75 mg/sq m IV over 1 hr Day 1 of each cycle<br>Drug: BNP7787<br>* 40 g IV over 30 min Day 1 of each cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | Toxicity profile w/ emphasis on incidence and severity of peripheral neuropathy, febrile neutropenia, and nephrotoxicity | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response |  | during tx,q 3 mon for 1 yr, then q 6 mon for 2 yrs | 
| Survival |  | q 6 mon for 2 yrs after registration, then annually | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anemia, drug/agent toxicity by tissue/organ, neutropenia, stage IV non-small cell lung cancer, stage IIIB non-small cell lung cancer, recurrent non-small cell lung cancer, squamous cell lung cancer, large cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer, adenosquamous cell lung cancer