Lung Cancer, Non-Small Cell
Conditions
Keywords
paclitaxel, NSCLC, pazopanib, Advanced Non-Small Cell Lung Cancer, non-small cell lung cancer, Advanced Solid Tumor, GW786034, Metastatic Non-Small Cell Lung Cancer
Brief summary
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.
Interventions
DRUGpazopanib
oral pazopanib once daily (Phase I starting dose 800 mg)
DRUGpaclitaxel
paclitaxel IV once every 3 weeks (Phase I starting dose 135 mg/m2).
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| Phase I: paclitaxel and pazopanib pharmacokinetics | Cycle 1 and Cycle 2 PK sampling |
| Phase I: clinical activity | at least 6 weeks |
Countries
United Kingdom, United States
Outcome results
None listed