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

A Phase 2 Study Evaluating the Efficacy of VEGF Trap in Patients With Recurrent Inoperable Stage III or Stage IV Melanoma

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Melanoma; Stage IV Melanoma; Ciliary Body and Choroid Melanoma, Medium/Large Size; Iris Melanoma; Metastatic Intraocular Melanoma; Recurrent Intraocular Melanoma; Stage III Melanoma; Extraocular Extension Melanoma
• Intervention / Treatment: Other: pharmacological study; Biological: ziv-aflibercept

Detailed Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Other: pharmacological study; Correlative studies; Other Names: pharmacological studies; Biological: ziv-aflibercept; Given IV; Other Names: aflibercept; vascular endothelial growth factor trap; VEGF Trap; Zaltrap

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (CR + PR)	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.",	Start of treatment to disease progression/recurrence, up to 5 years
4 Month Progression-free Survival	Estimated using the product-limit method of Kaplan and Meier. 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.	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Will be estimated by the Kaplan-Meier method.	From the initial date of treatment to the recorded date of death, assessed up to 5 years
Number of Participants With Toxicities	The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 were utilized for AE grading and reporting. Grade 3 and higher adverse events considered possibly, probably or definitely related to aflibercept are summarized.	Up to 5 years
Impact of the VEGF Trap Therapy on Laboratory Correlates		Up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ahmad Tarhini, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: March 20, 2007
• First Submitted That Met QC Criteria: March 20, 2007
• First Posted (Estimate): March 22, 2007

Study Record Updates

• Last Update Posted (Actual): May 24, 2018
• Last Update Submitted That Met QC Criteria: April 26, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Eye Diseases; Disease Attributes; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Uveal Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Eye Neoplasms; Recurrence; Melanoma; Uveal Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept; Endothelial Growth Factors
• Other Study ID Numbers: NCI-2009-00182 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P30CA033572 (U.S. NIH Grant/Contract); N01CM62209 (U.S. NIH Grant/Contract); 7522 (Other Identifier: CTEP); PHII-77 (Other Identifier: City of Hope); CDR0000535719