Pazopanib Hydrochloride or a Placebo in Treating Patients With Non-Small Cell Lung Cancer Who Have Received First-Line Chemotherapy
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.
Drug: pazopanib hydrochloride
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
Procedure: quality-of-life assessment
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Double Blind Randomized Phase III Study of Maintenance Pazopanib Versus Placebo in NSCLC Patients Non Progressive After First Line Chemotherapy. MAPPING, an EORTC Lung Group Study.|
- Overall survival [ Designated as safety issue: No ]
- Progression-free survival (PFS) overall and at 6 and 12 months [ Designated as safety issue: No ]
- Toxicity [ Designated as safety issue: Yes ]
- Correlation of C-reactive protein with PFS at weeks 6, 14, and 22 [ Designated as safety issue: No ]
- Quality of life [ Designated as safety issue: No ]
- Comparison of discontinuation rate with treatment compliance [ Designated as safety issue: No ]
- Health economics [ Designated as safety issue: No ]
|Study Start Date:||July 2011|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
2 weeks at 600mg and then maintenance at 800mg
|Drug: pazopanib hydrochloride Other: laboratory biomarker analysis Other: pharmacogenomic studies Other: pharmacological study Procedure: quality-of-life assessment|
Placebo Comparator: Placebo
placebo match 2 weeks at 600mg and then maintenance at 800mg
|Other: laboratory biomarker analysis Other: pharmacogenomic studies Other: pharmacological study Procedure: quality-of-life assessment|
- 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01208064
|Universitair Ziekenhuis Gent|
|Centre Hospitalier Regional De La Citadelle|
|Clinique et Maternité Sainte Elisabeth|
|National Cancer Institute|
|Assistance Publique - Hôpitaux de Marseille - Assistance Publique - Hôpitaux de Marseille - Hopital Nord|
|University General Hospital Heraklion|
|The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis|
|University Clinic Golnik|
|Royal Marsden - Surrey|
|Sutton, England, United Kingdom, SM2 5PT|
|Western General Hospital|
|Edinburgh, United Kingdom|
|Guy's and St Thomas' NHS|
|London, United Kingdom|
|Royal Marsden Hospital|
|London, United Kingdom|
|Christie NHS Foundation Trust|
|Manchester, United Kingdom|
|Nottingham University Hospitals NHS Trust|
|Nottingham, United Kingdom|
|Weston Park Hospital|
|Sheffield, United Kingdom|
|Royal Marsden Hospital|
|Sutton, United Kingdom|
|King's Mill Hospital|
|Sutton-in-Ashfield, United Kingdom|
|Principal Investigator:||Mary O'Brien, MD||Royal Marsden NHS Foundation Trust|