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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00871403
First received: March 26, 2009
Last updated: June 12, 2013
Last verified: March 2012
  Purpose

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 Intervention Phase
Lung Cancer, Non-Small Cell
Drug: pazopanib and pemetrexed
Drug: pemetrexed and cisplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Progression-free Survival (PFS) [ Time Frame: Randomization until progression or death (up to 85 weeks) ] [ Designated as safety issue: No ]
    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:
  • Overall Survival (OS) [ Time Frame: Randomization until death (up to 85 weeks) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Randomization until response or progressive disease (up to 85 weeks) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With a Complete Response or a Partial Response [ Time Frame: Randomization until response or progressive disease (up to 85 weeks) ] [ Designated as safety issue: No ]
    The percentage of participants with a complete response or a partial response was evaluated.


Enrollment: 107
Study Start Date: July 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00871403

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

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00871403     History of Changes
Other Study ID Numbers: 111128
Study First Received: March 26, 2009
Results First Received: January 26, 2012
Last Updated: June 12, 2013
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: Azienda Sanitaria Ospedaliera San Luigi Gonzaga
Belgium: Agence Fédérale des Médicaments et des Produits de la Santé
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Denmark: Danish Medicines Agency
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Netherlands: De Centrale Commissie Mensgebonden Onderzoek

Keywords provided by GlaxoSmithKline:
GW786034
pazopanib
pemetrexed
cisplatin
non-small cell lung cancer
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on October 02, 2014