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

Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00600821
• Other study ID #: A4061030
• Status: Completed
• Phase: Phase 2
• First received: January 3, 2008
• Last updated: October 16, 2013
• Start date: April 2008
• Est. completion date: October 2012

Study information

• Verified date: October 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: October 2012
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small-Cell Lung Carcinoma

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.
• 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.
• 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
• 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-
• 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.
• 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

Locations

Country	Name	City	State
Czech Republic	Pfizer Investigational Site	Praha 8
Czech Republic	Pfizer Investigational Site	Tabor
Czech Republic	Pfizer Investigational Site	Usti nad Labem
France	Pfizer Investigational Site	Caen Cedex 05
France	Pfizer Investigational Site	Paris Cedex 14
France	Pfizer Investigational Site	Pierre-Bénite
Poland	Pfizer Investigational Site	Bydgoszcz
Poland	Pfizer Investigational Site	Gdansk
Poland	Pfizer Investigational Site	Gdynia
Poland	Pfizer Investigational Site	Torun
Poland	Pfizer Investigational Site	Warszawa
Spain	Pfizer Investigational Site	Alicante
Spain	Pfizer Investigational Site	Mataro	Barcelona
Spain	Pfizer Investigational Site	Sabadell	Barcelona
Spain	Pfizer Investigational Site	Valencia
United Kingdom	Pfizer Investigational Site	Dundee	Scotland
United Kingdom	Pfizer Investigational Site	Dundee
United Kingdom	Pfizer Investigational Site	Leeds	Yorkshire
United Kingdom	Pfizer Investigational Site	London
United Kingdom	Pfizer Investigational Site	London
United Kingdom	Pfizer Investigational Site	Southampton	Hampshire
United Kingdom	Pfizer Investigational Site	Surrey
United States	Pfizer Investigational Site	Bartlett	Tennessee
United States	Pfizer Investigational Site	Baton Rouge	Louisiana
United States	Pfizer Investigational Site	Cleveland	Ohio
United States	Pfizer Investigational Site	Columbus	Mississippi
United States	Pfizer Investigational Site	Corinth	Mississippi
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Germantown	Tennessee
United States	Pfizer Investigational Site	Lincoln	Nebraska
United States	Pfizer Investigational Site	Lubbock	Texas
United States	Pfizer Investigational Site	Memphis	Tennessee
United States	Pfizer Investigational Site	Memphis	Tennessee
United States	Pfizer Investigational Site	New Albany	Mississippi
United States	Pfizer Investigational Site	Oxford	Mississippi
United States	Pfizer Investigational Site	Pittsfield	Massachusetts
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	San Antonio	Texas
United States	Pfizer Investigational Site	Southaven	Mississippi
United States	Pfizer Investigational Site	Tupelo	Mississippi
United States	Pfizer Investigational Site	Wenatchee	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Czech Republic,  France,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma Concentration Change in the Uridine Diphosphate Glucuronosyltransferase 1A1 (UGT1A1) Genotype	UGT1A1 an enzyme of the glucuronidation pathway that transforms small lipophilic molecules, such as steroids, bilirubin, hormones, and drugs, into water-soluble, excretable metabolites.	Baseline (Day 1 of Cycle 1)	No
Primary	Progression Free Survival (PFS)	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").	Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years	No
Secondary	Overall Survival (OS)	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).	Baseline, every 6 weeks until death or bimonthly after final study visit (up to 2.75 years)	No
Secondary	Percentage of Participants With Objective Response (OR)	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.	Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years	No
Secondary	Duration of Response (DR)	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.	Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years	No
Secondary	Population Pharmacokinetic (PK) Analysis for Axitinib (AG-013736)	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.	Pre-dose, 1 to 2 hours post-dose on Cycle 2 of Day 1 and Cycle 3 of Day 1	No
Secondary	European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score	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.	Day (D) 1 of every cycle (C) then every 3 weeks until final study visit (up to 2.75 years)	No
Secondary	European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Lung Cancer-13 (QLQ- LC13) Score	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.	Day 1 of every cycle then every 3 weeks until final study visit (up to 2.75 years)	No
Secondary	Percentage of Participants by Ribonucleic Acid (RNA) Expression Profile in Whole Blood	RNA expression profiles of genes which were associated with tumor growth, angiogenesis and metastases were collected and correlated with efficacy.	Baseline, C1 D1, C1 D15, C2 D1, C3 D1, C4 D1 and C5 D1	No
Secondary	Circulating Endothelial Cells (CEC) in Blood: Total CEC	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.	Baseline (C1 D1), C1 D15, C2 D1, C3 D1, C4 D1, C5 D1, C7 D1, C9 D1 and C11 D1	No
Secondary	Circulating Endothelial Cells (CEC) in Blood	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.	Baseline (C1 D1), C1 D15, C2 D1, C3 D1, C4 D1, C5 D1, C7 D1, C9 D1 and C11 D1	No
Secondary	Plasma Concentration of Soluble Proteins	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.	Baseline, C1D1, C1D15, C2D1, C3D1, C4D1, C5D1, C7D1, C9D1 and C11D1	No

External Links

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