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

Phase 2

Completed

Conditions: Lung Cancer, Non-Small Cell

Interventions: Drug: pemetrexed and cisplatin
Drug: pazopanib and pemetrexed

Registration Number: NCT00871403

Lead Sponsor: GlaxoSmithKline

Brief Summary: The main purpose of this study is to determine whether the combination of pazopanib and pemetrexed is safe and effective in the treatment of advanced non-small cell lung cancer (NSCLC).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 107

Inclusion Criteria

Written informed consent
At least 18 years old
Histologically- or cytologically-confirmed diagnosis of predominantly nonsquamous cell Stage IIIBwet (with confirmed malignant pleural effusion) or Stage IV NSCLC
No prior systemic first-line therapy for advanced NSCLC
Measurable disease
Eastern Cooperative Oncology Group (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, hepatic, and renal)
Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) OR childbearing potential, and agrees to use adequate contraception. A male with a female partner of childbearing potential is eligible if he uses a barrier method of contraception or abstinence during the study

Exclusion Criteria

Active malignancy or any malignancy in the 3 years prior to first dose of study drug other than NSCLC
Central nervous system (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, pemetrexed, and/or cisplatin
Inability to interrupt aspirin or other non-steroidal anti-inflammatory drugs during the study
Inability or unwillingness to take folic acid, vitamin B12 supplementation, or dexamethasone
Clinically significant third-space fluid collections (e.g., ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study start
Recent or concurrent yellow fever vaccination

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 2	pemetrexed and cisplatin	Standard treatment (pemetrexed and cisplatin)
Arm 1	pazopanib and pemetrexed	Investigational treatment (pazopanib and pemetrexed)

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	Randomization until progression or death (up to 85 weeks)	PFS is defined as the interval between the date of randomization (date on which the investigator evaluated the participant and first determined he/she had disease progression) and the first occurrence of progressive disease (PD) or death from any cause. Per Response Evaluation Criteria in Solid Tumors (RECIST), version 1, PD is defined as a \>=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of \>=1 new lesion).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With a Complete Response or a Partial Response	Randomization until response or progressive disease (up to 85 weeks)	The percentage of participants with a complete response or a partial response was evaluated.
Overall Survival (OS)	Randomization until death (up to 85 weeks)	OS was determined from the date of randomization to the date of death from any cause. Participants who had not died at the time of the cut-off for the final analysis were censored at the date the participants were last known to be alive. Because enrollment in the study was halted prematurely, the ability to achieve an estimate of OS was compromised. Consequently, OS was not estimated.
Best Overall Response, Assessed as the Number of Participants With the Indicated Tumor Response: Investigator Assessed Only	Randomization until response or progressive disease (up to 85 weeks)	Tumor response was assessed by the Investigator according to the RECIST, version 1.0. A participant was defined as a responder if he/she sustained a complete response (CR; the disappearance of all target lesions) or partial response (PR; \>=30% decrease in the sum of the longest diameter of target lesions) for at least 4 weeks at any time during randomized treatment. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.