NCT00284141

Brief Summary

This study evaluated the efficacy and safety of aflibercept in the treatment of participants with advanced chemoresistant non-small cell lung adenocarcinoma (NSCLA). Primary objective:

  • To determine the overall objective response rate (ORR) of AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®) 4.0 mg/kg intravenously (IV) every 2 weeks in participants with platinum- and erlotinib-resistant, locally advanced or metastatic NSCLA. Secondary objective:
  • To assess duration of response (DR), progression-free survival (PFS), and overall survival (OS) in this participant population
  • To evaluate the safety profile of IV AVE0005 (ziv-aflibercept, aflibercept, VEGF trap, ZALTRAP®). This study employed an Independent Review Committee (IRC) for radiological tumor assessments. For all tumor assessment-related efficacy variables, two analyses were performed: the primary analysis was based on Independent Review Committee (IRC) reviewed data and the secondary analysis was based on Investigator evaluation. In addition, both Response Evaluation Criteria In Solid Tumors (RECIST) and Modified Response Evaluation Criteria In Solid Tumors (mRECIST) were used to assess tumors. Where as RECIST criteria only consider the longest diameter of the tumors for calculations pertaining to changes in tumor size, mRECIST assessments also account for the differences in the cavities of lesions observed in non-small-cell lung cancer (NSCLC). Responses based on RECIST and mRECIST are reported.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
98

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2006

Geographic Reach
3 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2006

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

January 30, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

January 31, 2006

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2008

Completed
4.4 years until next milestone

Results Posted

Study results publicly available

December 10, 2012

Completed
Last Updated

December 10, 2012

Status Verified

July 1, 2011

Enrollment Period

2.5 years

First QC Date

January 30, 2006

Results QC Date

August 17, 2012

Last Update Submit

November 12, 2012

Conditions

Pulmonary DiseasesNeoplasms, Lung

Keywords

lungcancernon-small-cell lung cancermetastaticcarcinomalung neoplasmlung diseasesangiogenesisanti-angiogenesisanti-angiogenesis inhibitorscancer and other neoplasmsrespiratory tract(lung and bronchial) diseases

Outcome Measures

Primary Outcomes (2)

  • Confirmed Objective Response (OR) Based Upon Modified Response Evaluation Criteria in Solid Tumors (RECIST) Assessed by the Independent Review Committee (IRC).

    OR was either complete response (CR) or partial response (PR) based on RECIST or modified RECIST. CR was the disappearance of all target/nor-target lesions; and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with reference to the baseline sum LD (According to modified RECIST, to calculate LD for cavitated lesions, the longest cavitation diameters were subtracted from the LD of cavitated target lesions). Assessments were made by the IRC, and confirmed by repeat tumor imaging 4-6 weeks after documentation of the initial response.

    up to 2.5 years from initial treatment

  • Confirmed Objective Response Based Upon Modified Response Evaluation Criteria in Solid Tumors (RECIST) Assessed by the Investigator.

    OR was either complete response (CR) or partial response (PR) based on RECIST or modified RECIST. CR was the disappearance of all target/nor-target lesions; and PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, with reference to the baseline sum LD (According to modified RECIST, to calculate LD for cavitated lesions, the longest cavitation diameters were subtracted from the LD of cavitated target lesions). Assessments were made by the Investigator, and confirmed by repeat tumor imaging 4-6 weeks after documentation of the initial response.

    up to 2.5 years from initial treatment

Secondary Outcomes (10)

  • Duration of Response (DR)

    up to 2.5 years from initial treatment

  • Progression-free Survival (PFS) Time Assessed by the Independent Review Committee (IRC)

    up to 2.5 years from initial treatment

  • Progression-free Survival (PFS) Time Assessed by the Investigator

    up to 2.5 years from initial treatment

  • Overall Survival (OS)

    up to 2.5 years from initial treatment

  • Heath-related Quality of Life (QOL) Measured Via the Lung Cancer Subscale

    Baseline to 2.5 years

  • +5 more secondary outcomes

Study Arms (1)

aflibercept 4.0 mg/kg

EXPERIMENTAL

Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept every 2 weeks until a study withdrawal criterion was met.

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

Interventions

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

Aflibercept 4.0 mg/kg administered intravenously (IV) over a period of at least 1 hour once every 2 weeks. Aflibercept could be reduced by 1 dose level (to 3.0 mg/kg) or 2 dose levels (to 2.0 mg/kg) in case of uncontrolled hypertension or urinary protein \>3.5 g/24 hours. Intrapatient dose escalation was not to be permitted. Participants requiring more than 2 dose level reductions would be withdrawn from study treatment.

aflibercept 4.0 mg/kg

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed non-small-cell lung adenocarcinoma that is locally advanced or metastatic
  • Prior treatment with at least 2 cancer drug regimens in the advanced disease setting
  • Platinum- and erlotinib-resistant disease defined by relapse or progression during or after treatment
  • Measurable disease by RECIST criteria
  • ECOG Performance status less than or equal to 2
  • Resolution of any toxic effects of prior therapy
  • Adequate organ and bone marrow function
  • Female patients must be post-menopausal, surgically sterile or using effective contraception
  • Willing and able to comply with study procedures and sign informed consent

You may not qualify if:

  • Diagnosis of squamous-cell lung cancer or any second malignancy within the last 5 years (except for adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri)
  • Prior treatment with a VEGF or VEGF receptor inhibitor with the exception of bevacizumab (Avastin-TM)
  • Anticipation of a need for major surgical procedure
  • Treatment with chemotherapy, radiotherapy, surgery, blood products, or an investigational agent within 3 weeks (6 weeks for nitrosoureas, mitomycin C, immunotherapy, or cytokine therapy) of study enrollment
  • Uncontrolled hypertension
  • Any severe or acute medical or psychiatric problem within the past 6 months requiring further investigation or that may cause undue risk for the patient's safety
  • History of brain metastases, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
  • Active infection or on antiretroviral therapy for HIV disease
  • Pregnant or breast-feeding
  • The above information is not intended to contain all considerations relevant to potential participation in a clinical trial.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

Sanofi-Aventis Administrative Office

Laval, Canada

Location

Sanofi-Aventis Administrative Office

Paris, France

Location

Related Publications (1)

  • Leighl NB, Raez LE, Besse B, Rosen PJ, Barlesi F, Massarelli E, Gabrail N, Hart LL, Albain KS, Berkowitz L, Melnyk O, Shepherd FA, Sternas L, Ackerman J, Shun Z, Miller VA, Herbst RS. A multicenter, phase 2 study of vascular endothelial growth factor trap (Aflibercept) in platinum- and erlotinib-resistant adenocarcinoma of the lung. J Thorac Oncol. 2010 Jul;5(7):1054-9. doi: 10.1097/jto.0b013e3181e2f7fb.

    PMID: 20593550RESULT

MeSH Terms

Conditions

Lung DiseasesLung NeoplasmsNeoplasmsCarcinoma, Non-Small-Cell LungNeoplasm MetastasisCarcinomaDisease

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Respiratory Tract DiseasesRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteCarcinoma, BronchogenicBronchial NeoplasmsNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Glandular and EpithelialNeoplasms by Histologic Type

Results Point of Contact

Title
Trial Transparency Team
Organization
Sanofi
Contact-Us@Sanofi.com

Study Officials

  • ICD CSD

    Sanofi

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 30, 2006

First Posted

January 31, 2006

Study Start

January 1, 2006

Primary Completion

July 1, 2008

Study Completion

July 1, 2008

Last Updated

December 10, 2012

Results First Posted

December 10, 2012

Record last verified: 2011-07

Locations

FR(1)US(1)CA(1)