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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00600821
First received: January 3, 2008
Last updated: October 16, 2013
Last verified: October 2013
  Purpose

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


Condition Intervention Phase
Non-Small-Cell Lung Carcinoma
Adenocarcinoma
Drug: Bevacizumab
Drug: Carboplatin
Drug: Paclitaxel
Drug: AG-013736 (axitinib)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years ] [ Designated as safety issue: No ]
    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:
  • Overall Survival (OS) [ Time Frame: Baseline, every 6 weeks until death or bimonthly after final study visit (up to 2.75 years) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Plasma Concentration Change in the Uridine Diphosphate Glucuronosyltransferase 1A1 (UGT1A1) Genotype [ Time Frame: Baseline (Day 1 of Cycle 1) ] [ Designated as safety issue: No ]
    UGT1A1 an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites.


Enrollment: 118
Study Start Date: April 2008
Study Completion Date: October 2012
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: B
Bevacizumab will be administered in combination with carboplatin and paclitaxel.
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
Experimental: A
AG-013736 will be administered in combination with carboplatin and paclitaxel.
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
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00600821

  Show 44 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00600821     History of Changes
Other Study ID Numbers: A4061030
Study First Received: January 3, 2008
Results First Received: April 20, 2012
Last Updated: October 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Bevacizumab
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014