A Study of Aflibercept Versus Placebo in Patients With Second-Line Docetaxel for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (VITAL)

• ClinicalTrials.gov Identifier: NCT00532155
• Recruitment Status: Completed
• First Posted: September 20, 2007
• Results First Posted: January 1, 2013
• Last Update Posted: June 7, 2016
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

Study Description

Brief Summary:

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 or disease	Intervention/treatment	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

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)

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 913 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, 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
• Study Start Date: September 2007
• Actual Primary Completion Date: January 2011
• Actual Study Completion Date: October 2011

Arms and Interventions

Arm	Intervention/treatment
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).

Outcome Measures

Primary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: Baseline to the date when 687 deaths occurred (26 January 2011) ]

   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 :

1. Progression Free Survival (PFS) [ Time Frame: Baseline to data cut-off (26 January 2011) ]

   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.

2. Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria [ Time Frame: Baseline to data cut-off (26 January 2011) ]

   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.

3. 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. ]
   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).
4. 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. ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, New Jersey

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States, 08807

Argentina

Sanofi-Aventis Administrative Office

Buenos Aires, Argentina

Australia, New South Wales

sanofi-aventis Australia & New Zealand administrative office

Macquarie Park, New South Wales, Australia

Austria

Sanofi-Aventis Administrative Office

Wien, Austria

Brazil

Sanofi-Aventis Administrative Office

Sao Paulo, Brazil

Bulgaria

Sanofi-Aventis Administrative Office

Sofia, Bulgaria

Canada

Sanofi-Aventis Administrative Office

Laval, Canada

Chile

Sanofi-Aventis Administrative Office

Santiago, Chile

China

Sanofi-Aventis Administrative Office

Shangai, China

Czech Republic

Sanofi-Aventis Administrative Office

Praha, Czech Republic

Estonia

Sanofi-Aventis Administrative Office

Tallinn, Estonia

Finland

Sanofi-Aventis Administrative Office

Helsinki, Finland

France

Sanofi-Aventis Administrative Office

Paris, France

Germany

Sanofi-Aventis Administrative Office

Berlin, Germany

Greece

Sanofi-Aventis Administrative Office

Athens, Greece

Hong Kong

Sanofi-Aventis Administrative Office

Causeway Bay, Hong Kong

Hungary

Sanofi-Aventis Administrative Office

Budapest, Hungary

India

Sanofi-Aventis Administrative Office

Mumbai, India

Italy

Sanofi-Aventis Administrative Office

Milano, Italy

Korea, Republic of

Sanofi-Aventis Administrative Office

Seoul, Korea, Republic of

Malaysia

Sanofi-Aventis Administrative Office

Kuala Lumpur, Malaysia

Netherlands

Sanofi-Aventis Administrative Office

Gouda, Netherlands

Poland

Sanofi-Aventis Administrative Office

Warszawa, Poland

Portugal

Sanofi-Aventis Administrative Office

Porto Salvo, Portugal

Romania

Sanofi-Aventis Administrative Office

Bucuresti, Romania

Russian Federation

Sanofi-Aventis Administrative Office

Moscow, Russian Federation

Singapore

Sanofi-Aventis Administrative Office

Singapore, Singapore

Spain

Sanofi-Aventis Administrative Office

Barcelona, Spain

Sweden

Sanofi-Aventis Administrative Office

Bromma, Sweden

Taiwan

Sanofi-Aventis Administrative Office

Taipei, Taiwan

Turkey

Sanofi-Aventis Administraive Office

Istanbul, Turkey

United Kingdom

Sanofi-Aventis Admnistrative Office

Guildford Surrey, United Kingdom

Sponsors and Collaborators

Sanofi

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

Publications of Results:

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
• Other Study ID Numbers: EFC10261; EudraCT 2007-000819-29
• First Posted: September 20, 2007
• Results First Posted: January 1, 2013
• Last Update Posted: June 7, 2016
• Last Verified: May 2016

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; Docetaxel; 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; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action