Clinical trial NCT00284141
Conditions: Pulmonary Diseases Neoplasms, Lung
Keywords: lung cancer non-small-cell lung cancer metastatic carcinoma lung neoplasm lung diseases angiogenesis anti-angiogenesis anti-angiogenesis inhibitors cancer and other neoplasms respiratory tract (lung and bronchial) diseases
Sponsor: Sanofi
Start date: 2006-01-01; Completion date: 2008-07-01
Enrollment: 98 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

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.

Detailed description:
The study included :

* A screening phase up to 21 days followed by registration
* Treatment initiation within 5 working days of registration
* A treatment phase with 14-day study treatment cycles until a study withdrawal criterion was met or up to the clinical database cut-off date (18 July 2008)
* A follow-up phase - up to 60 days after end of treatment

Withdrawal criteria that led to treatment discontinuation were:

* The participant or their legally authorized representative requested to withdraw
* In the investigator's opinion, continuation of the study would be detrimental to the participant's well being, due to reasons such as disease progression, unacceptable toxicity, noncompliance, or logistical considerations.
* A specific request by the Sponsor
* Participant had intercurrent illness that prevented further administration of study treatment
* Participant had more than 2 aflibercept dose reductions
* Participant had arterial thromboembolic events, including cerebrovascular accidents, myocardial infarctions, transient ischemic attacks, new onset or worsening of pre-existing angina
* Participant had radiographic evidence of intestinal obstruction (e.g., dilated loops of bowel accompanied by air-fluid levels) or gastrointestinal perforation (e.g., presence of extraluminal gas) requiring surgical intervention
* Participant was lost to follow-up

After discontinuing treatment, participants remained on the study until the last post-treatment visit or until recovery of drug related toxicities, whichever was later.

Arms: arm 1: Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept every 2 weeks until a study withdrawal criterion was met.
Interventions: intervention 1: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®)
Intervention descriptions: intervention 1: 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.

Protocol documents: