VEGF Trap in Treating Patients With Recurrent Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: March 20, 2007
Last updated: February 2, 2015
Last verified: April 2013
This phase II trial is studying how well VEGF Trap works in treating patients with recurrent stage III or stage IV melanoma that cannot be removed by surgery. Combinations of biological substances in VEGF Trap may be able to carry tumor-killing substances directly to melanoma cells. It may also stop the growth of melanoma by blocking blood flow to the tumor.

Condition Intervention Phase
Ciliary Body and Choroid Melanoma, Medium/Large Size
Extraocular Extension Melanoma
Iris Melanoma
Metastatic Intraocular Melanoma
Recurrent Intraocular Melanoma
Recurrent Melanoma
Stage III Melanoma
Stage IV Melanoma
Biological: ziv-aflibercept
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study Evaluating the Efficacy of VEGF Trap in Patients With Recurrent Inoperable Stage III or Stage IV Melanoma

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective Response Rate (CR + PR) [ Time Frame: Start of treatment to disease progression/recurrence, up to 5 years ] [ Designated as safety issue: No ]
    Using the RECIST v1.0 criteria for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response = CR + PR.",

  • 4 Month PFS Rate in Comparison With Historical Data [ Time Frame: 4 months ] [ Designated as safety issue: No ]

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    The targeted 4-months PFSR was based on three recently reported (at the time of study design) phase III randomized clinical trials with a median of 2.3 months PFS as a conservative external standard. If this regimen's improved median PFS from 2.3 to 4 months, corresponding to an improvement in the 4-month PFSR from 30% to 50% using a constant hazard model, we concluded that it would warrant further study. The study design yields a 85% power to detect a true 4-month PFS rate of at least 50%.

Secondary Outcome Measures:
  • Overall Survival [ Time Frame: From the initial date of treatment to the recorded date of death, assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be estimated by the Kaplan-Meier method.

  • Toxicities Assessed Using NCI CTCAE v3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
  • Impact of the VEGF Trap Therapy on Laboratory Correlates [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: June 2007
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive Aflibercept IV at 4 mg/kg over 1 hour on day 1. Treatment repeats every 14 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.
Biological: ziv-aflibercept
Given IV
Other Names:
  • aflibercept
  • vascular endothelial growth factor trap
  • VEGF Trap
  • Zaltrap
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:


I. Determine the antitumor response rate (complete and partial response) in patients with recurrent inoperable stage III or IV melanoma treated with VEGF Trap.

II. Compare the progression-free survival of patients treated with this regimen vs historical controls.


I. Determine the overall survival of patients treated with this regimen. II. Determine the toxicity and tolerability of this regimen in these patients. III. Determine the impact of this regimen on laboratory correlates including anti-VEGF Trap antibody testing and pharmacokinetics in these patients.

OUTLINE: This is a multicenter study.

Patients receive VEGF Trap IV over 1 hour on day 1. Treatment repeats every 14 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline, prior to course 2, and 60 days after completion of study treatment for pharmacokinetic and pharmacodynamic studies. Samples are analyzed by enzyme-linked immunosorbent assay.

After completion of study treatment, patients are followed periodically for 5 years.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed stage III or IV melanoma
  • Cutaneous, ocular, or mucosal melanoma allowed
  • Recurrent, inoperable disease
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
  • No evidence of CNS disease, including primary brain tumor or brain metastases
  • No brain metastases by MRI or CT scan within the past 4 weeks
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • Life expectancy > 3 months
  • WBC ≥ 3,000/mm³
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 75,000/mm³
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
  • Urine protein:creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine collection
  • PT INR ≤ 1.5 unless on full-dose warfarin
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to agents used in the study
  • No serious or nonhealing wound, ulcer, or bone fracture
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No significant traumatic injury within the past 28 days
  • No clinically significant cardiovascular disease, including any of the following:

    • Cerebrovascular accident within the past 6 months
    • Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg or systolic BP > 180 mm Hg if diastolic BP < 90 mm Hg within the past 3 months
    • Myocardial infarction, coronary artery bypass graft, or unstable angina within the past 6 months
    • New York Heart Association class III-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Unstable angina pectoris within the past 6 months
    • Clinically significant peripheral vascular disease within the past 6 months
    • Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
    • No evidence of bleeding diathesis or coagulopathy
  • No concurrent uncontrolled illness, including, but not limited to any of the following:

    • Ongoing or active infection
    • Psychiatric illness or social situation that would preclude study compliance
  • Recovered from all prior therapy and major surgery
  • No prior chemotherapy or hormonal therapy
  • More than 7 days since prior core visceral organ biopsy
  • More than 4 weeks since prior biologic therapy or radiotherapy
  • More than 28 days since prior major surgery or open biopsy
  • No concurrent major surgery
  • No other concurrent investigational agents
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • Concurrent full-dose warfarin with PT INR > 1.5 allowed provided the following criteria are met:

    • INR in range (2-3) on a stable dose of oral anticoagulant or low molecular weight heparin
    • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  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 identifier: NCT00450255

United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Ahmad Tarhini University of Pittsburgh
  More Information

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00450255     History of Changes
Other Study ID Numbers: NCI-2009-00182  NCI-2009-00182  PHII-77  CDR0000535719  PHII-77  7522  N01CM62209  P30CA033572 
Study First Received: March 20, 2007
Results First Received: April 22, 2014
Last Updated: February 2, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Uveal Neoplasms
Eye Diseases
Eye Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Uveal Diseases
Endothelial Growth Factors
Growth Substances
Physiological Effects of Drugs processed this record on May 26, 2016