A Multicenter, Open-label, Single-arm, Two-stage Study of the Efficacy and Safety of AVE0005 (VEGF Trap) Administered Intravenously Every 2 Weeks in Patients With Platinum- and Erlotinib-resistant Locally Advanced or Metastatic Non-small-cell Lung Adenocarcinoma
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Sanofi
- Enrollment
- 98
- Locations
- 1
- Primary Endpoint
- Confirmed Objective Response (OR) Based Upon Modified Response Evaluation Criteria in Solid Tumors (RECIST) Assessed by the Independent Review Committee (IRC).
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
aflibercept 4.0 mg/kg
Participants with metastatic non-small-cell lung adenocarcinoma administered 4.0 mg/kg Aflibercept every 2 weeks until a study withdrawal criterion was met.
Intervention: Aflibercept (ziv-aflibercept, AVE0005, VEGF trap, ZALTRAP®) (Drug)
Outcomes
Primary Outcomes
Confirmed Objective Response (OR) Based Upon Modified Response Evaluation Criteria in Solid Tumors (RECIST) Assessed by the Independent Review Committee (IRC).
Time Frame: up to 2.5 years from initial treatment
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.
Confirmed Objective Response Based Upon Modified Response Evaluation Criteria in Solid Tumors (RECIST) Assessed by the Investigator.
Time Frame: up to 2.5 years from initial treatment
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.
Secondary Outcomes
- Number of Participants With Anti-drug Antibodies(up to 2.5 years after initial treatment)
- 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)
- Overall Safety - Number of Participants With Adverse Events(up to 60+/-5 days after treatment discontinuation, or or until TEAE was resolved or stabilized (Collected till 18 July 2008))
- Number of Participants With Laboratory Abnormalities(Up to 2.5 years)
- Peak of Free Aflibercept (VEGF Trap)(Day 1 of the first infusion of Aflibercept (cycle 1))
- Free and VEGF-bound Trough Aflibercept Concentrations (VEGF Trap)(At the end of each treatment cycle (up to 2.5 years))