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Pazopanib Hydrochloride or a Placebo in Treating Patients With Non-Small Cell Lung Cancer Who Have Received First-Line Chemotherapy

Phase 2
Terminated
Conditions
Lung Cancer
Interventions
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
Procedure: quality-of-life assessment
Registration Number
NCT01208064
Lead Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Brief Summary

RATIONALE: Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether pazopanib hydrochloride is more effective than a placebo in treating patients with non-small cell lung cancer that has not progressed after first-line chemotherapy.

PURPOSE: This randomized phase II/III trial is studying how well giving pazopanib hydrochloride works and compares it with giving a placebo in treating patients with non-small cell lung cancer who have received first-line chemotherapy.

Detailed Description

OBJECTIVES:

Primary

* To compare the therapeutic benefit, in terms of overall survival, of maintenance pazopanib hydrochloride in patients with non-small cell lung cancer who have not progressed after first-line chemotherapy.

Secondary

* To compare progression-free survival (PFS) overall and at specific time points (6 and 12 months).

* To document the toxicity profile of pazopanib hydrochloride according to the CTCAE v 4.

* To assess the use of C-reactive protein (CRP) in the detection of progression of disease in the maintenance phase of therapy.

* To compare quality-of-life of patients on maintenance therapy.

* To compare discontinuation rate/treatment compliance of patients treated with these regimens.

* To collect health economics data on resource utilization as documented by the EQ-5D generic QoL instrument.

Tertiary (correlative)

* To evaluate the effect of germline genetic variations on drug response (pharmacogenetics) using PAX gene.

* To find relevant biomarkers of VEGFR pathways from plasma samples.

* To obtain the pharmacokinetics of pazopanib hydrochloride at 600 and 800 mg.

* To evaluate biomarkers in tumor tissue.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to center, histology (squamous vs nonsquamous), performance status (0-1 vs 2 up to 15% of patients), and response to initial chemotherapy (complete response/partial response vs stable disease). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive an oral placebo daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

* Arm II: Patients receive oral pazopanib hydrochloride daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients complete quality-of life-questionnaires (QLQ-C30 and QLQ-LC13) at baseline, 6 weeks, 14 weeks, and 22 weeks.

Health economics data on resource utilization are collected and documented using the EQ-5D questionnaire.

Blood samples may be collected periodically for pharmacokinetics and pharmacogenetic studies. Samples are analyzed for germline genetic variations on drug response, relevant biomarkers of VEGFR pathways, and concentration of pazopanib hydrochloride. Previously collected tumor tissue is analyzed for biomarkers.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
102
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Pazopanibpazopanib hydrochloride2 weeks at 600mg and then maintenance at 800mg
Placebopharmacological studyplacebo match 2 weeks at 600mg and then maintenance at 800mg
Placeboquality-of-life assessmentplacebo match 2 weeks at 600mg and then maintenance at 800mg
Pazopanibquality-of-life assessment2 weeks at 600mg and then maintenance at 800mg
Placebolaboratory biomarker analysisplacebo match 2 weeks at 600mg and then maintenance at 800mg
Pazopanibpharmacological study2 weeks at 600mg and then maintenance at 800mg
Placebopharmacogenomic studiesplacebo match 2 weeks at 600mg and then maintenance at 800mg
Pazopaniblaboratory biomarker analysis2 weeks at 600mg and then maintenance at 800mg
Pazopanibpharmacogenomic studies2 weeks at 600mg and then maintenance at 800mg
Primary Outcome Measures
NameTimeMethod
Overall survival
Secondary Outcome Measures
NameTimeMethod
Progression-free survival (PFS) overall and at 6 and 12 months
Correlation of C-reactive protein with PFS at weeks 6, 14, and 22
Toxicity
Health economics
Quality of life
Comparison of discontinuation rate with treatment compliance

Trial Locations

Locations (21)

Klinik Loewenstein

🇩🇪

Loewenstein, Germany

University General Hospital Heraklion

🇬🇷

Heraklion, Greece

UniversitaetsMedizin Mannheim

🇩🇪

Mannheim, Germany

Western General Hospital

🇬🇧

Edinburgh, United Kingdom

University Clinic Golnik

🇸🇮

Golnik, Slovenia

Royal Marsden Hospital

🇬🇧

Sutton, United Kingdom

Guy's and St Thomas' NHS

🇬🇧

London, United Kingdom

Christie NHS Foundation Trust

🇬🇧

Manchester, United Kingdom

Nottingham University Hospitals NHS Trust

🇬🇧

Nottingham, United Kingdom

Weston Park Hospital

🇬🇧

Sheffield, United Kingdom

King's Mill Hospital

🇬🇧

Sutton-in-Ashfield, United Kingdom

Clinique et Maternité Sainte Elisabeth

🇧🇪

Namur, Belgium

Universitair Ziekenhuis Gent

🇧🇪

Gent, Belgium

Centre Hospitalier Regional De La Citadelle

🇧🇪

Liege, Belgium

The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis

🇳🇱

Amsterdam, Netherlands

National Cancer Institute

🇪🇬

Cairo, Egypt

Centre Georges-Francois-Leclerc

🇫🇷

Dijon, France

Isala Klinieken

🇳🇱

Zwolle, Netherlands

Assistance Publique - Hôpitaux de Marseille - Assistance Publique - Hôpitaux de Marseille - Hopital Nord

🇫🇷

Marseille, France

Amphia Ziekenhuis

🇳🇱

Breda, Netherlands

Royal Marsden - Surrey

🇬🇧

Sutton, England, United Kingdom

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