Monotherapy Pazopanib in Subjects With Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This study is designed to evaluate the efficacy and safety of monotherapy pazopanib (a small molecule tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGF, and c-kit) in subjects with advanced (Stage IIIB or IV) non-small cell lung cancer.

Detailed Description
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Study 109609 is a single-arm, non-randomized, single-stage Phase II study of pazopanib in subjects with Stage IIIB or IV non-small cell lung cancer who have progressed after one or two prior regimens of systemic therapy. The study will be conducted at a limited number of institutions in the US. A total of 40 evaluable subjects will be enrolled and treated. Pazopanib will be given at a dose of 800mg (as determined by previous Phase I studies) orally once per day. Subjects may continue to receive study drug for up to two years unless they experience disease progression or withdraw from treatment for other reasons, or unless the Sponsor terminates the study. A rollover study may be available to those subjects who are exhibiting clinical benefit (stable disease or better). Evaluable subjects will be assessed for response as the primary endpoint.

Official Title
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A Phase II, Non-randomized, Multi-center Study to Evaluate the Efficacy and Safety of Pazopanib (GW786034) in Subjects With Advanced Non-Small Cell Lung Cancer

Conditions
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Lung Cancer, Non-Small Cell

Intervention / Treatment
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* Drug: Pazopanib (GW786034)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed consent Histologically- or cytologically confirmed diagnosis of Stage IIIB or IV non-small cell lung cancer. Failed no more than two prior chemotherapy regimens for Stage IIIB or IV non-small cell lung cancer, including a platinum-containing regimen. Brain metastases permitted if subject has been treated with surgery and/or radiation therapy more than 4 weeks prior to date of first dose and is stable for at least one week off steroids. 18 years of age or older. Eastern Cooperative Oncology Group performance status of at least 2. Measurable disease according to RECIST. Adequate organ system function. Females may be eligible to enroll if they are of non-childbearing potential (surgically sterile or post-menopausal)or are using appropriate contraception methods. Exclusion Criteria: Prior malignancy - unless disease-free for at least 3 years, or have had completely resected non-melanomatous skin cancer or successfully treated in situ carcinoma. History or clinical evidence of central nervous system metastases or leptomeningeal carcinomatosis, except for subjects with previously-treated CNS metastases, who are asymptomatic, and have had no requirement for steroids or anti-seizure medication for one week prior to first dose of study drug. Clinically significant gastrointestinal abnormalities. Presence of uncontrolled infection. Corrected QT interval greater than 480 msec. History of significant cardiovascular condition(s). Poorly controlled hypertension (systolic blood pressure of 140mmHG or greater or diastolic blood pressure of 90mmHg or greater). History of cerebrovascular accident, pulmonary embolism, or insufficiently treated deep venous thrombosis within the past 6 months prior to first dose of study drug. Major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. Active bleeding or diathesis. Hemoptysis in excess of 2.5mL within 8 weeks of first dose of study drug. Serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance with study procedures. Use of prohibited medications as defined in protocol. Use of an investigational agent, including an investigational anti-cancer agent within 28 days, or 5 half-lives, whichever is longer, prior to first dose of study drug. Prior use of any investigational or licensed anti-angiogenic agent, including thalidomide and agents that target platelet-derived growth factor. Prior treatment with bevacizumab or epidermal growth factor receptor tyrosine kinase inhibitors

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pazopanib Open-label<br>Single-arm, non-randomised, single-stage pazopanib monotherapy. | Drug: Pazopanib (GW786034)<br>* Pazopanib monotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved Either a Confirmed Complete Response or Partial Response Per RECIST Criteria | The best overall response using Response Evaluation Criteria In Solid Tumors (RESIST) was measured. Complete response is defined as the disappearance of all known lesion(s), confirmed at 4 weeks, and partial response is defined as at least a 30% decrease in the sum of the longest diameters of target lesions taken as a reference to baseline sum of the longest diameters, confirmed at 4 weeks. No formal efficacy analyses were performed due to early termination of the study. | Baseline through End of Study (up to 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Had a Complete or Partial Response, or Stable Disease | Disease control was measured. Stable disease (SD) is defined as neither partial response (at least a 30% decrease in the sum of the longest diameters of target lesions taken as a reference to baseline sum of the longest diameters, confirmed at 4 weeks) nor progressive disease (PD; a 20% increase in the sum of the longest diameters of target lesions, taken as a reference the smallest sum of the longest diameter recorded since the treatment started or the appearance of one or more new lesions. No formal efficacy analyses were performed due to early termination of the study. | Baseline through End of Study (up to 2 years) | 
| Progression-Free Survival | Progression-free survival is defined as the interval between the start of treatment and the earliest date of disease progression or death due to any cause, whichever occurs first. No formal efficacy analyses were performed due to early termination of the study. | Baseline through End of Study (up to 2 years) | 
| Overall Survival | Overall survival is defined as the time from the start of treatment until death due to any cause. No formal efficacy analyses were performed due to early termination of the study. | Baseline through End of Study (up to 2 years) | 
| Levels of Circulating Biomarkers in Plasma | Biomarkers are proteins that respond in a unique way to treatment with the study drug; however, levels of proteins were not collected for this measurement. No formal efficacy analyses were performed due to early termination of the study. | Baseline through End of Study (up to 2 years) | 
| Characterization of Participant Populations by Identification of Intra-tumoral Biomarkers | Biomarkers are proteins that respond in a unique way to treatment with the study drug; however, levels of proteins were not collected for this measurement. No formal efficacy analyses were performed due to early termination of the study. | Baseline through End of Study (up to 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anti-angiogenesis, Non-small cell lung cancer,, pazopanib (GW786034)