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

• ClinicalTrials.gov Identifier: NCT00871403
• Recruitment Status: Completed
• First Posted: March 30, 2009
• Results First Posted: February 16, 2012
• Last Update Posted: June 20, 2013
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Lung Cancer, Non-Small Cell	Drug: pazopanib and pemetrexed; Drug: pemetrexed and cisplatin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multicentre, Randomised Phase II Study of Pazopanib in Combination With Pemetrexed in First-line Treatment of Subjects With Predominantly Non-squamous Cell Stage IIIBwet/IV Non-small Cell Lung Cancer
• Study Start Date: July 2009
• Actual Primary Completion Date: March 2011
• Actual Study Completion Date: March 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 1; Investigational treatment (pazopanib and pemetrexed)	Drug: pazopanib and pemetrexed; oral pazopanib 600 mg once daily and pemetrexed intravenous (IV) 500mg/m^2 once every 3 weeks, then pazopanib 800 mg once daily
Active Comparator: Arm 2; Standard treatment (pemetrexed and cisplatin)	Drug: pemetrexed and cisplatin; pemetrexed IV 500 mg/m^2 and cisplatin IV 75 mg/m^2 once every 3 weeks

Outcome Measures

Primary Outcome Measures :

1. Progression-free Survival (PFS) [ Time Frame: 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 :

1. Overall Survival (OS) [ Time Frame: 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.
2. Best Overall Response, Assessed as the Number of Participants With the Indicated Tumor Response: Investigator Assessed Only [ Time Frame: 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.
3. Percentage of Participants With a Complete Response or a Partial Response [ Time Frame: Randomization until response or progressive disease (up to 85 weeks) ]
   The percentage of participants with a complete response or a partial response was evaluated.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Denmark

GSK Investigational Site

Herlev, Denmark, 2730

United Kingdom

GSK Investigational Site

Sutton, Surrey, United Kingdom, SM2 5PT

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00871403
• Other Study ID Numbers: 111128
• First Posted: March 30, 2009
• Results First Posted: February 16, 2012
• Last Update Posted: June 20, 2013
• Last Verified: March 2012

Keywords provided by GlaxoSmithKline:

GW786034; pazopanib; pemetrexed; cisplatin; non-small cell lung cancer; NSCLC

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors