Study of Pazopanib and Paclitaxel in Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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The Phase I part of the study will identify the doses of pazopanib and paclitaxel that can be administered safely in combination. The Phase II part of the study will not be progressed as documented in Protocol Amendment 01.

Official Title
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An Open-label, Multicenter, Phase I/II Study of Pazopanib in Combination With Paclitaxel in First-line Treatment of Subjects With Stage IIIBwet/IV Non-small Cell Lung Cancer

Conditions
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Lung Cancer, Non-Small Cell

Intervention / Treatment
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* Drug: pazopanib
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent At least 18 years old Histologically- or cytologically-confirmed diagnosis of Stage IIIBwet (with confirmed malignant pleural effusion) or Stage IV NSCLC (or for Phase I only, advanced solid tumor for which there is no standard therapy or for whom paclitaxel is standard therapy). No prior systemic first-line therapy for advanced disease Measurable disease ECOG performance status of 0 or 1 Life expectancy of at least 12 weeks. Able to swallow and retain oral medication Adequate organ system function (hematological, renal, and hepatic) Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) OR childbearing potential, and agrees to use adequate contraception Exclusion Criteria: Active malignancy or any malignancy in the 3 years prior to first dose of study drug other than NSCLC (or for Phase I, other than the primary solid tumor) CNS metastases or leptomeningeal carcinomatosis, except for asymptomatic, previously treated CNS metastases Clinically significant gastrointestinal abnormalities Prolongation of corrected QT interval (QTc) > 480 msecs History of any one or more cardiovascular conditions within the past 6 months prior to randomization Poorly controlled hypertension History of cerebrovascular accident (including transient ischemic attacks), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months Major surgery or trauma within 28 days or any non-healing wound, fracture, or ulcer Evidence of active bleeding or bleeding diathesis Recent hemoptysis Endobronchial lesions and/or lesions infiltrating major pulmonary vessels Serious and/or unstable pre-existing medical (e.g., uncontrolled infection), psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures Use of any prohibited medication Use of an investigational agent within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug Ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity except alopecia Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib, paclitaxel, and/or carboplatin.

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: Phase I<br>oral pazopanib once daily (Phase I starting dose 800 mg) and paclitaxel IV once every 3 weeks (Phase I starting dose 135 mg/m2). | Drug: pazopanib<br>* oral pazopanib once daily (Phase I starting dose 800 mg)<br>* Other names: Votrient;Drug: paclitaxel<br>* paclitaxel IV once every 3 weeks (Phase I starting dose 135 mg/m2).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: safety and tolerability (Serious adverse events, adverse events, dose-limiting toxicities, clinical laboratory data, vital signs, ECG, ECOG performance status) |  | at least one cycle of treatment (3 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: paclitaxel and pazopanib pharmacokinetics |  | Cycle 1 and Cycle 2 PK sampling | 
| Phase I: clinical activity |  | at least 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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paclitaxel, NSCLC, pazopanib, Advanced Non-Small Cell Lung Cancer, non-small cell lung cancer, Advanced Solid Tumor, GW786034, Metastatic Non-Small Cell Lung Cancer