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

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer, Non-Small Cell
• Intervention / Treatment: Drug: pazopanib; Drug: paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • GSK Investigational Site
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • GSK Investigational Site
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • GSK Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I; 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; oral pazopanib once daily (Phase I starting dose 800 mg); Other Names: Votrient; Drug: paclitaxel; paclitaxel IV once every 3 weeks (Phase I starting dose 135 mg/m2).

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2009
• Primary Completion (Actual): October 25, 2012
• Study Completion (Actual): October 25, 2012

Study Registration Dates

• First Submitted: March 19, 2009
• First Submitted That Met QC Criteria: March 19, 2009
• First Posted (Estimate): March 20, 2009

Study Record Updates

• Last Update Posted (Actual): November 13, 2017
• Last Update Submitted That Met QC Criteria: November 8, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: NSCLC; non-small cell lung cancer; paclitaxel; Advanced Solid Tumor; pazopanib; GW786034; Metastatic Non-Small Cell Lung Cancer; Advanced Non-Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: 111109