A Study Of AG-013736 (Axitinib) Or Bevacizumab (Avastin) In Combination With Paclitaxel And Carboplatin In Patients With Advanced Lung Cancer.

Phase 2

Completed

• Conditions: Non-Small-Cell Lung Carcinoma; Adenocarcinoma
• Interventions: Drug: Bevacizumab; Drug: AG-013736 (axitinib); Drug: Carboplatin; Drug: Paclitaxel

• Registration Number: NCT00600821
• Lead Sponsor: Pfizer

Brief Summary

To determine if the addition of AG-013736 to chemotherapy is beneficial in patients with advanced lung cancer who have not been previously treated.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-01-03
• Study First Submitted QC: 2008-01-13
• Study First Posted: 2008-01-25
• Study Start: 2008-04
• Disposition First Submitted: 2010-02-11
• Disposition First Submitted QC: 2010-02-11
• Disposition First Posted: 2010-02-15
• Primary Completion: 2011-04
• Results First Submitted: 2012-04-20
• Results First Submitted QC: 2012-04-21
• Results First Posted: 2012-05-22
• Study Completion: 2012-10
• Status Verified: 2013-10
• Last Update Submitted: 2013-10-16
• Last Update Posted: 2013-11-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 118

Inclusion Criteria

• Advanced non squamous cell, lung cancer
• No prior treatment for lung cancer except prior adjuvant therapy if last dose was >12 months prior to enrollment

Exclusion Criteria

• Prior therapy for advanced lung cancer
• The need for blood-thinners
• Coughing up blood

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B	Bevacizumab	Bevacizumab will be administered in combination with carboplatin and paclitaxel.
A	AG-013736 (axitinib)	AG-013736 will be administered in combination with carboplatin and paclitaxel.
B	Carboplatin	Bevacizumab will be administered in combination with carboplatin and paclitaxel.
B	Paclitaxel	Bevacizumab will be administered in combination with carboplatin and paclitaxel.
A	Carboplatin	AG-013736 will be administered in combination with carboplatin and paclitaxel.
A	Paclitaxel	AG-013736 will be administered in combination with carboplatin and paclitaxel.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years	Time in months from start of study treatment to first randomization date of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the first randomization date plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was "Death").

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Baseline, every 6 weeks until death or bimonthly after final study visit (up to 2.75 years)	Time in months from date of randomization to date of death due to any cause. OS was calculated as (the death date minus the first randomization date plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).
Percentage of Participants With Objective Response (OR)	Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years	OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR: disappearance of all lesions (target and/or non target) and no appearance of new lesions. PR: at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, without progression of non target lesions and no appearance of new lesions.
Duration of Response (DR)	Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years	Time in months from the first documentation of objective tumor response that is subsequently confirmed to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Population Pharmacokinetic (PK) Analysis for Axitinib (AG-013736)	Pre-dose, 1 to 2 hours post-dose on Cycle 2 of Day 1 and Cycle 3 of Day 1	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score	Day (D) 1 of every cycle (C) then every 3 weeks until final study visit (up to 2.75 years)	EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhoea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.
European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Lung Cancer-13 (QLQ- LC13) Score	Day 1 of every cycle then every 3 weeks until final study visit (up to 2.75 years)	QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnoea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
Percentage of Participants by Ribonucleic Acid (RNA) Expression Profile in Whole Blood	Baseline, C1 D1, C1 D15, C2 D1, C3 D1, C4 D1 and C5 D1	RNA expression profiles of genes which were associated with tumor growth, angiogenesis and metastases were collected and correlated with efficacy.
Circulating Endothelial Cells (CEC) in Blood: Total CEC	Baseline (C1 D1), C1 D15, C2 D1, C3 D1, C4 D1, C5 D1, C7 D1, C9 D1 and C11 D1	Circulating endothelial cells (CECs) are noninvasive marker of vascular damage, remodeling, and dysfunction. Total CEC, plasma-vascular endothelial growth factor receptor-2 (pVEGFR2), VEGFR2, p-Beta-type platelet-derived growth factor receptor (pPDGFRB+) and PDGFRB+ were explored using CECs. Blood was collected to analyze effects of therapy on the number, viability/apoptotic state, and/or target activity/expression in CECs.
Circulating Endothelial Cells (CEC) in Blood	Baseline (C1 D1), C1 D15, C2 D1, C3 D1, C4 D1, C5 D1, C7 D1, C9 D1 and C11 D1	Circulating endothelial cells (CECs) are noninvasive marker of vascular damage, remodeling, and dysfunction. Total CEC, plasma-vascular endothelial growth factor receptor-2 (pVEGFR2), VEGFR2, p-Beta-type platelet-derived growth factor receptor (pPDGFRB+) and PDGFRB+ were explored using CECs. Blood was collected to analyze effects of therapy on the number, viability/apoptotic state, and/or target activity/expression in CECs.
Plasma Concentration of Soluble Proteins	Baseline, C1D1, C1D15, C2D1, C3D1, C4D1, C5D1, C7D1, C9D1 and C11D1	Plasma concentrations of soluble proteins (soluble- stem-cell factor receptor (sKIT) vascular endothelial growth factor \[VEGF\], and vascular endothelial growth factor receptor-2 \[VEGFR2\], VEGFR3) may be associated with tumor angiogenesis or tumor physiology and may correlate with efficacy or biological activity. It is presented as ratio to baseline, which is obtained by dividing the plasma soluble protein concentration at each time point by its concentration at baseline.

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇬🇧 Surrey, United Kingdom