A Study of Aflibercept Versus Placebo in Patients With Second-Line Docetaxel for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer - Full Text View

Purpose

The primary objective of the study was to demonstrate overall survival improvement for aflibercept + docetaxel compared to docetaxel + placebo as second line treatment for participants with locally advanced or metastatic non-small cell lung cancer (NSCLC).

The secondary objectives were to compare other efficacy parameters, to assess the overall safety of the two treatment arms, to assess the pharmacokinetics of intravenous (IV) aflibercept in this participant population and to determine immunogenicity of IV aflibercept in all participants.

Condition	Intervention	Phase
Carcinoma Non Small Cell Lung	Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) Drug: Placebo Drug: Docetaxel (Taxotere®) Drug: Dexamethasone (pre- and post-medication for docetaxel)	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Multinational, Randomized, Double-Blind Study Comparing Aflibercept Versus Placebo in Patients Treated With Second-Line Docetaxel After Failure of One Platinum Based Therapy for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Dexamethasone Dexamethasone acetate Docetaxel Aflibercept

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:

Overall Survival (OS) [ Time Frame: Baseline to the date when 687 deaths occurred (26 January 2011) ] [ Designated as safety issue: No ]
OS was time interval from the date of randomization to the date of death due to any cause. If death was not observed during the study, overall survival time was censored at the last date the participant was known to be alive, or the study cutoff date, whichever was earlier. The cut-off date for the OS was date when 687 deaths were observed.

OS was estimated from Kaplan-Meier Curves.

Secondary Outcome Measures:

Progression Free Survival (PFS) [ Time Frame: Baseline to data cut-off (26 January 2011) ] [ Designated as safety issue: No ]
PFS was defined as the time interval between the date of randomization and the time of occurrence of the first radiological tumor progression detected by a computer tomography (CT) scan and /or by Magnetic Resonance Imaging (MRI); or death due to any cause; whichever was earlier. Participants without disease progression were censored at the earliest date between their last valid tumour assessment and the data cutoff date.

PFS was estimated from Kaplan-Meier Curves.
Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria [ Time Frame: Baseline to data cut-off (26 January 2011) ] [ Designated as safety issue: No ]
Participants with OR were those who had a confirmed complete response [CR] or a confirmed partial response [PR], based on RECIST criteria, in which
- CR refected the disappearance of all tumor lesions (with no new tumors)
- PR reflected a pre-defined decrease in tumor burden - a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
- OR was CR + PR The response rate was the percent of participants with a response.
To determine a response, tumors were assessed by the investigators using Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and an observed response was confirmed by repeated imaging after 4 - 6 weeks.
Health Related Quality of Life (HRQL) Assessed by the Lung Cancer Symptom Scale (LCSS) [ Time Frame: Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy. ] [ Designated as safety issue: No ]
HRQL assessments were performed by participants using a self-administered LCSS questionnaire. LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies (appetite, fatigue, cough, dyspnea, hemoptysis and pain), and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. The LCSS total score was defined as the mean of the 9 items of the scale, each scored between 0 (for best outcome) to 100 (for worst outcome).
Health Related Quality of Life (HRQL) Assessed by the Average Symptom Burden Index (ASBI) [ Time Frame: Baseline (prior to first dose), at cycles 2 and 4 and at the end of study therapy. ] [ Designated as safety issue: No ]
HRQL assessments were performed by participants using a self-administered LCSS questionnaire. LCSS is a 9-item questionnaire, six measuring major symptoms for lung malignancies, and 3 summation items related to total symptomatic distress, activity status and overall quality of life. Participant responses were measured using visual analogue scales (VAS) with 100-mm lines. ABSI was the mean score for the six major lung cancer symptoms (appetite, fatigue, cough, dyspnea, hemoptysis and pain), each scored between 0 (for best outcome) to 100 (for worst outcome).


Enrollment:	913
Study Start Date:	September 2007
Study Completion Date:	October 2011
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Placebo/Docetaxel Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Drug: Placebo Matching placebo to Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks. Drug: Docetaxel (Taxotere®) 75 mg/m² docetaxel in 250 mL dextrose 5% or NaCl 0.9% administered intravenously (IV) over 1 hour, on Day 1 every 3 weeks. Drug: Dexamethasone (pre- and post-medication for docetaxel) As a pre- and post-medication for docetaxel, 8 mg dexamethasone was administered orally, the evening before Day 1, on Day 1 (early morning, 1 hour before docetaxel treatment, and evening) and on Day 2 (morning and evening).
Placebo Comparator: Aflibercept/Docetaxel Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.	Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) 6 mg/kg Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks. Drug: Docetaxel (Taxotere®) 75 mg/m² docetaxel in 250 mL dextrose 5% or NaCl 0.9% administered intravenously (IV) over 1 hour, on Day 1 every 3 weeks. Drug: Dexamethasone (pre- and post-medication for docetaxel) As a pre- and post-medication for docetaxel, 8 mg dexamethasone was administered orally, the evening before Day 1, on Day 1 (early morning, 1 hour before docetaxel treatment, and evening) and on Day 2 (morning and evening).

Arms

Assigned Interventions

Experimental: Placebo/Docetaxel

Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Placebo immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.

Drug: Placebo

Matching placebo to Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks.

Drug: Docetaxel (Taxotere®)

75 mg/m² docetaxel in 250 mL dextrose 5% or NaCl 0.9% administered intravenously (IV) over 1 hour, on Day 1 every 3 weeks.

Drug: Dexamethasone (pre- and post-medication for docetaxel)

As a pre- and post-medication for docetaxel, 8 mg dexamethasone was administered orally, the evening before Day 1, on Day 1 (early morning, 1 hour before docetaxel treatment, and evening) and on Day 2 (morning and evening).

Placebo Comparator: Aflibercept/Docetaxel

Participants with Non-Small-Cell Lung Cancer (NSCLC) were administered Aflibercept immediately followed by Docetaxel every three weeks until disease progression, unacceptable toxicity, or participant's refusal.

Drug: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)

6 mg/kg Aflibercept administered intravenously (IV) over 1 hour once on Day 1, every 3 weeks.

Drug: Docetaxel (Taxotere®)

75 mg/m² docetaxel in 250 mL dextrose 5% or NaCl 0.9% administered intravenously (IV) over 1 hour, on Day 1 every 3 weeks.

Drug: Dexamethasone (pre- and post-medication for docetaxel)

As a pre- and post-medication for docetaxel, 8 mg dexamethasone was administered orally, the evening before Day 1, on Day 1 (early morning, 1 hour before docetaxel treatment, and evening) and on Day 2 (morning and evening).

Detailed Description:

The study included:

A screening visit of up to 21 days prior to randomization
Randomization at baseline (Treatment was initiated with 3 days of randomization)
A treatment period with 3-week treatment cycles until the participant met the following discontinuation criteria: had progressive disease, had unacceptable toxicity, or refused further study treatment
A post study treatment follow-up period (a visit was scheduled every 8 weeks until death or end of study)

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histological/cytological proven locally advanced or metastatic non-small cell lung cancer
Disease progression during or after one, and only one, prior anticancer therapy which is platinum-based for advanced or metastatic disease
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
Adequate renal, liver and bone marrow functions

Exclusion Criteria:

Squamous histology/cytology
Less than 28 days elapsed from prior treatment with radiotherapy, surgery, or chemotherapy to the time of randomization
Prior isotope therapy, whole pelvic radiotherapy, or radiotherapy to > 25% of bone marrow
Prior docetaxel treatment
Uncontrolled hypertension

The above information was not intended to contain all considerations relevant to participation in a clinical trial.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00532155

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Sponsors and Collaborators

Sanofi

Regeneron Pharmaceuticals

Investigators


Study Director:	Clinical Sciences & Operations	Sanofi

More Information

Publications:

Ramlau R, Gorbunova V, Ciuleanu TE, Novello S, Ozguroglu M, Goksel T, Baldotto C, Bennouna J, Shepherd FA, Le-Guennec S, Rey A, Miller V, Thatcher N, Scagliotti G. Aflibercept and Docetaxel versus Docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol. 2012 Oct 10;30(29):3640-7. doi: 10.1200/JCO.2012.42.6932. Epub 2012 Sep 10.


Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT00532155 History of Changes
Other Study ID Numbers:	EFC10261 EudraCT 2007-000819-29
Study First Received:	September 19, 2007
Results First Received:	August 17, 2012
Last Updated:	May 4, 2016
Health Authority:	United States: Food and Drug Administration Poland: Ministry of Health Spain: Spanish Agency of Medicines

Keywords provided by Sanofi:


lung cancer angiogenesis inhibitor chemotherapy

Additional relevant MeSH terms:


Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Dexamethasone acetate Dexamethasone Dexamethasone 21-phosphate Docetaxel BB 1101	Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Tubulin Modulators

ClinicalTrials.gov processed this record on September 29, 2016

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