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

• ClinicalTrials.gov Identifier: NCT00600821
• Recruitment Status: Completed
• First Posted: January 25, 2008
• Results First Posted: May 22, 2012
• Last Update Posted: November 8, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: January 3, 2008
• First Posted Date: January 25, 2008
• Results First Submitted Date: April 20, 2012
• Results First Posted Date: May 22, 2012
• Last Update Posted Date: November 8, 2013
• Study Start Date: April 2008
• Actual Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 21, 2012)

Progression Free Survival (PFS) [ Time Frame: 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").

• Original Primary Outcome Measures (submitted: January 13, 2008): Progression Free Survival [ Time Frame: 2.5 yrs ]

Current Secondary Outcome Measures (submitted: April 21, 2012)

• Overall Survival (OS) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: January 13, 2008)

• Overall Survival [ Time Frame: 3 yrs ]
• Overall confirmed objective response rate [ Time Frame: 2.5 yrs ]
• Duration of response [ Time Frame: 2.5 yrs ]
• Overall safety profile [ Time Frame: 2.5 yrs ]
• Population PK [ Time Frame: 2.5 yrs ]
• Molecular profiling and biomarkers [ Time Frame: 2.5 yrs ]

Current Other Pre-specified Outcome Measures (submitted: April 21, 2012)

Plasma Concentration Change in the Uridine Diphosphate Glucuronosyltransferase 1A1 (UGT1A1) Genotype [ Time Frame: Baseline (Day 1 of Cycle 1) ]

UGT1A1 an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites.

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Of AG-013736 (Axitinib) Or Bevacizumab (Avastin) In Combination With Paclitaxel And Carboplatin In Patients With Advanced Lung Cancer.
• Official Title: Randomized Phase 2 Trial Of AG013736 Or Bevacizumab In Combination With Paclitaxel And Carboplatin As First Line Treatment For Patients With Advanced Non Small Cell Lung Cancer
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Small-Cell Lung Carcinoma
• Adenocarcinoma

Intervention

• Drug: Bevacizumab
  Bevacizumab is available as 100 and 400 mg preservative-free, single use vials- The starting dose is 15 mg/kg, iv infusion, every 3 weeks.
  Other Name: Avastin
• Drug: Carboplatin
  Carboplatin is available as pre-mixed 10mg /ml aqueous solution- The starting dose is AUC 6 mg*min/ml, iv infusion, every 3 weeks.
• Drug: Paclitaxel
  Paclitaxel is available in multidose vials (30 mg/5ml;100mg/16.7 ml;300 mg/50ml)- The starting dose is 200 mg/m2, every 3 weeks
• Drug: AG-013736 (axitinib)
  AG-013736 (axitinib) is available as 1mg, and 5 mg film-coated tablets for oral administration- The starting dose is 5 mg BID-
  Other Name: axitinib Taxol

Study Arms

• Active Comparator: B
  Bevacizumab will be administered in combination with carboplatin and paclitaxel.
  Interventions:

  • Drug: Bevacizumab
  • Drug: Carboplatin
  • Drug: Paclitaxel
• Experimental: A
  AG-013736 will be administered in combination with carboplatin and paclitaxel.
  Interventions:

  • Drug: AG-013736 (axitinib)
  • Drug: Carboplatin
  • Drug: Paclitaxel

• Publications *: Twelves C, Chmielowska E, Havel L, Popat S, Swieboda-Sadlej A, Sawrycki P, Bycott P, Ingrosso A, Kim S, Williams JA, Chen C, Olszanski AJ, de Besi P, Schiller JH. Randomised phase II study of axitinib or bevacizumab combined with paclitaxel/carboplatin as first-line therapy for patients with advanced non-small-cell lung cancer. Ann Oncol. 2014 Jan;25(1):132-8. doi: 10.1093/annonc/mdt489.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 30, 2012): 118
• Original Estimated Enrollment (submitted: January 13, 2008): 108
• Actual Study Completion Date: October 2012
• Actual Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Czech Republic, France, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT00600821
• Other Study ID Numbers: A4061030
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: October 2013