Docetaxel With or Without PI-88 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, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PI-88 may stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. It may also help docetaxel work better by making tumor cells more sensitive to the drug. Giving docetaxel together with PI-88 may kill more tumor cells. It is not yet known whether giving docetaxel together with PI-88 is more effective than docetaxel alone in treating non-small cell lung cancer. PURPOSE: This randomized phase II trial is studying docetaxel and PI-88 to see how well they work when given together compared to docetaxel 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 safety and efficacy of docetaxel with vs without PI-88 in patients with stage IIIB or IV non-small cell lung cancer. Secondary Determine the efficacy markers of docetaxel and PI-88 in these patients. Determine the safety and potential efficacy of PI-88 alone as maintenance therapy in patients whose disease has been controlled with docetaxel and PI-88 combination therapy. Determine the safety and potential efficacy of PI-88 alone as third-line therapy in these patients. OUTLINE: This is an open-label, randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive docetaxel IV over 1 hour on days 1, 8, and 15. Arm II: Patients receive docetaxel as in arm I. Patients also receive PI-88 subcutaneously once daily on days 1-4, 8-11, and 15-18. In both arms, treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients in arm II with stable or responding disease after 6 courses may continue to receive PI-88 alone as maintenance therapy. Patients in arm I with progressive disease or unacceptable toxicity before the completion of 6 courses may receive PI-88 alone as third-line therapy. PROJECTED ACCRUAL: Approximately 100 patients will be accrued for this study.

Official Title
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A Phase II Study of Docetaxel With PI-88 in Patients With Advanced Non-Small-Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: PI-88
* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of non-small cell lung cancer Stage IIIB or IV disease Eligible for second-line docetaxel Disease progression during or after completion of prior first-line therapy comprising radiotherapy and/or platinum-based chemotherapy PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy At least 2 months Hematopoietic Neutrophil count > 1,500/mm^3 Platelet count > 100,000/mm^3 WBC > 3,000/mm^3 No history of thrombotic thrombocytopenic purpura or other platelet disease Hepatic Bilirubin normal ALT and AST ≤ 2.5 times upper limit of normal (ULN) (1.5 times ULN if alkaline phosphatase > 2.5 times ULN) Alkaline phosphatase ≤ 5 times ULN (unless bone metastases are present) PT < 1.5 times ULN Activated PTT normal Renal Creatinine clearance or glomerular filtration rate > 50mL/min Cardiovascular None of the following within the past 3 months: Myocardial infarction Stroke Congestive heart failure Immunologic No history of immune-mediated thrombocytopenia No evidence of anti-heparin antibodies No history of allergy and/or hypersensitivity to anti-coagulants or thrombolytic agents, especially heparin No history of allergy to polysorbate 80 No uncontrolled or serious infection within the past 4 weeks Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics No prior docetaxel Endocrine therapy Not specified Radiotherapy See Disease Characteristics More than 3 months since prior radiotherapy to > 30% of marrow-bearing bone Concurrent local palliative radiotherapy allowed Surgery More than 4 weeks since prior major surgery Other More than 4 weeks since prior antineoplastic therapy More than 2 weeks since prior and no concurrent heparin or low-molecular weight heparin More than 4 weeks since prior investigational therapy No concurrent aspirin or aspirin-containing medications except low-dose aspirin (≤ 100 mg/day) No concurrent nonsteroidal anti-inflammatory drugs except cyclooxygenase-2 inhibitors No concurrent warfarin or warfarin-containing medications except low-dose warfarin (≤ 1 mg/day) No concurrent antiplatelet drugs, including any of the following: Abciximab Clopidogrel Dipyridamole Ticlopidine Tirofiban No concurrent drugs that may inhibit docetaxel metabolism, including any of the following: Cyclosporine Terfenadine Ketoconazole Erythromycin Troleandomycin No other concurrent investigational drugs No other concurrent antineoplastic therapy

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 |
| --- | --- |
| Active Comparator: docetaxel<br>treated with docetaxel alone | Drug: docetaxel<br>* docetaxel only<br>|
| Experimental: PI-88+docetaxel<br>treated with docetaxel and PI-88 | Drug: PI-88<br>* PI-88+docetaxel<br>Drug: docetaxel<br>* docetaxel only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who are progression-free as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v2.0 at 6 months |  |  | 
| Non-progression rate as measured by RECIST v2.0 at 6 months |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression as measured by RECIST v2.0 at baseline, and then week 4 of courses 2, 3, 4, and 6 |  |  | 
| Response rate as measured by RECIST v2.0 at baseline, and then week 4 of courses 2, 3, 4, and 6 |  |  | 
| Quality of life as measured by Lung Cancer Symptom Scale (LCSS) every month |  |  | 
| Overall survival as measured by RECIST v2.0 at death |  |  | 

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