Pazopanib As Pre-Surgical Therapy In Treatment-Naive Subjects With Non-Small Cell Lung Cancer
- Conditions
- Non-Small Cell Lung CancerLung Cancer, Non-Small Cell
- Interventions
- Registration Number
- NCT00367679
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This is a phase 2 open-label, multicenter, non-randomized study to evaluate the safety and efficacy of oral pazopanib as neoadjuvant treatment for patients with stage 1A, 1B, IIA or IIB (to T2) resectable Non-Small Cell Lung Cancer (NSCLC).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Single Arm Pazopanib 800 mg pazopanib oral daily
- Primary Outcome Measures
Name Time Method Number of Participants Achieving Tumor Shrinkage Based on Change in Tumor Volume Baseline to at least two weeks or at most six weeks Tumor shrinkage was assessed as the change in tumor volume using high-resolution computed tomography scans of the thorax following treatment with pazopanib. Response is defined as the number of participants achieving at least 50% tumor volume reduction following pazopanib treatment. "Responder" is a participant whose tumor volume reduced at least 50% following pazopanib treatment. "Non-responder" is a participant whose tumor volume did not reduce at least 50% following treatment. Tumor assessments were conducted by a central reviewer.
- Secondary Outcome Measures
Name Time Method Number of Participants Achieving a Clinical Response Based on RECIST Baseline to at least two weeks or at most six weeks Response is the number of participants achieving either complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR, all detectable tumor has disappeared; PR, a \>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum; Progressive disease (PD), a \>=20% increase in target lesions; Stable Disease, small changes not meeting previously given criteria. Confirmation requires at least 2 assessments (conducted by a central reviewer) of CR/PR with at least 4 weeks between the assessments.
Number of Participants Achieving a >=60% Reduction in Tumor Metabolic Activity Determined as Standard Uptake Value (SUV) Baseline to at least two weeks or at most six weeks Response is the number of participants whose tumor demonstrated a 60% or greater reduction in metabolic activity (SUV) as measured by positron emission tomography (PET) or PET/computed tomography (PET/CT) at the end of treatment visit relative to baseline. This analysis was not conducted because insufficient data were collected: only three participants had PET/CT data.
Number of Participants With Shifts From Baseline to Grade 2 or Greater in Hematology Values Baseline to at least three weeks and at most 8 weeks Shifts in hematology values by grade were summarized based on the National Institutes of Health (NIH) Common Terminology Criteria for Adverse Events (Version 3.0 - definitions provided with each parameter below). Shifts to Grade 2 or greater at any point in the study following baseline are reported here.
Number of Participants With Shifts From Baseline to Grade 2 or Greater in Chemistry Values Baseline to at least three weeks and at most 8 weeks Shifts in chemistry values by grade were summarized based on the NIH Common Terminology Criteria for Adverse Events (Version 3.0 - definitions provided with each parameter below). Shifts to Grade 2 or greater at any point in the study following baseline are reported here. ULN = upper limit of normal; Gr = grade; mg = milligrams; dL = deciliter; mmol = millimoles.
Number of Participants With the Indicated Change From Baseline in Systolic and Diastolic Blood Pressure Baseline to at least three weeks and at most 8 weeks Increases in systolic or diastolic blood pressure values at any point in the study following baseline were summarized. mmHg = millimeters of mercury. Baseline blood pressure values as well as the change from baseline experienced are given in the category titles.
Number of Cells Exhibiting Apoptosis in Participant Samples Baseline to at least three weeks and at most 8 weeks (surgery date) Tumor cells from pre-treatment and post-operative biopsies were to have been analyzed to determine the number of cells that were exhibiting apoptosis. Due to the limited quantity of tissue in pre- and post-treatment biopsy samples, these assays were not performed.
Ratio of Post- to Pretreatment Expression Levels for Each of the Indicated Pazopanib Target Genes Baseline to at least three weeks and at most 8 weeks (surgery date) Gene expression data analysis was performed with GeneSpring GX 7.3.1 (Agilent Technologies). Data were preprocessed using the RMA algorithm. The Benjamini and Hochberg false discovery rate was used for multiple testing corrections. Data below are log-transformed ratios of the post-treatment to pre-treatment expression intensity, indicating the fold increase/decrease in expression of genes. PDGF, platelet-derived growth factor; VEGFR, vascular endothelial growth factor receptor; c-KIT, a protein tyrosine kinase that is a receptor for stem cell factor or "kit" ligand.
Gene Mutations in Pre- or Post-treatment Tumor Biopsies Baseline to at least three weeks and at most 8 weeks (surgery date) Specific genes (KRAS, MYC, TP53, and others) were to have been analyzed for the presence or absence of amplifications or deletions and for the presence, absence, and sequence of point mutations in pre- or post-treatment tumor biopsies. These analyses were not conducted because the potential results were considered to provide overlapping information with those obtained in the transcriptional and proteomic profiling assays that were conducted. The clinical study report indicates that genetic measures were to have been reported separately.
Intratumoral Levels of Specific Biomarkers Baseline tumor biopsy A pre-treatment tumor biopsy from each participant was to have been analyzed by Western blotting to semi-quantitate levels of various proteins related to angiogenesis and/or to the mechanism of action of pazopanib. These assays were not carried out due to insufficient quantity of tissue present in the pre-treatment biopsy (fine needle aspirate). The clinical study report indicates that results were to have been reported separately.
Plasma Levels of Lactate Dehydrogenase-5 (LDH5) Baseline to at least three weeks and at most 8 weeks LDH5 has been shown to be associated with activation of angiogenesis in lung cancer. Circulating levels of LDH5 were to have been measured at each scheduled visit through the post-treatment visit to determine if a correlation with drug effect existed. Levels of LDH5 were measured, but the team determined that greater value was to be derived from transcriptional and plasma biomarker analyses; thus, no analyses were conducted to examine the correlation of LDH5 levels with effects of pazopanib.
Genetic Variations in Germline DNA Baseline Plasma samples were collected from each consenting participant, generally at baseline, to permit evaluation of the presence or absence of genetic variations in select candidate genes in germline DNA. Analyses that could have been done might have examined the relationship between genetic variants and the safety or tolerability or the efficacy of pazopanib. Analyses have not yet been conducted, but a need to do so may yet be identified. The clinical study report indicated that results, if any, would be reported separately.
Semiquantitative Levels of Staining in Pre-treatment Tumor Biopsies (e.g. VEGF, VEGFR-1,VEGFR-2). Entire study interval Analysis not performed as part of study. Appropriate material was not available for analysis.
Ratio of Post- to Pretreatment Expression Levels for Each of the Indicated Pazopanib Target Proteins Baseline to at least two weeks and at most 6 weeks Baseline and post-therapy plasma samples were obtained from participants. Immunohistochemistry analyses were carried out using a BioPlex 200 machine (Bio-Rad) or by enzyme-linked immunoassays to evaluate levels of angiogenesis-related proteins and other relevant proteins. Post- and pre-treatment changes in cytokines and angiogenic factors in response to pazopanib were analyzed. A negative value indicates that the post-treatment level of the particular target protein was less than the pre-treatment level.
Trial Locations
- Locations (1)
GSK Investigational Site
🇪🇸Barcelona, Spain