Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Intravenous VEGF Trap in Treating Patients With Relapsed or Refractory Advanced Solid Tumors or Non-Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	MSKCC-03137 REGENERON-VGFT-ST-0202, NCT00083213

Objectives

Primary

1. Determine the safety and tolerability of intravenous VEGF Trap in patients with relapsed or refractory advanced solid tumors or non-Hodgkin's lymphoma.

Secondary

1. Determine the maximum tolerated intravenous dose of this drug in these patients.
2. Determine the pharmacokinetics of this drug in these patients.
3. Determine the ability of this drug to bind circulating vascular endothelial growth factor in these patients.
4. Determine, preliminarily, the ability of this drug to alter tumor blood flow and tumor vascular permeability in these patients.
5. Determine whether antibodies to this drug develop in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed diagnosis of one of the following:
  • Non-Hodgkin's lymphoma
  • Primary or metastatic solid tumor located, by radiography, in at least one of the following sites:
    • Liver
    • Soft tissue
    • Pelvis
    • Other site that is suitable for delayed contrast-enhanced MRI (e.g., peripheral lung field)



• Relapsed or refractory (including unresectable) disease
  • Patients with solid tumors must have failed all curative chemotherapeutic regimens
  • Patients with non-Hodgkin's lymphoma must be refractory to at least 2 standard chemotherapeutic regimens and rituximab



• Not amenable to available conventional therapies AND no standard therapy exists



• Measurable disease



• No prior or concurrent CNS metastases (brain or leptomeningeal)



• No primary intracranial tumor by MRI or CT scan



• No histologically confirmed squamous cell carcinoma of the lung

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• No prior participation in a VEGF Trap, interleukin-1 Trap, or interleukin-4/13 Trap clinical trial
• At least 3 weeks since prior immunotherapy and recovered
• No concurrent epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy and recovered

Endocrine therapy

• No concurrent adrenal corticosteroids except low-dose replacement therapy
• No concurrent systemic hormonal contraceptive agents

Radiotherapy

• At least 3 weeks since prior radiotherapy and recovered

Surgery

• At least 3 weeks since prior major or laparoscopic surgery and recovered
• More than 6 months since prior surgical procedure for correction or prophylaxis of peripheral vascular insufficiency or cerebral ischemic events

Other

• More than 30 days since prior investigational drugs
• No concurrent anticoagulant or antiplatelet drugs (e.g., warfarin, heparin, or aspirin) other than low-dose (1 mg) warfarin for maintaining patency of venous access devices
• No concurrent non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 (COX-2) inhibitors
• No other concurrent anticancer investigational agents
• No other concurrent anticancer therapy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,500/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 100,000/mm³
• No severe or uncontrolled hematologic condition

Hepatic

• Bilirubin ≤1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• PT and PTT normal
• INR normal
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative

Renal

• Creatinine ≤ ULN
• Urine protein/creatinine ratio ≤ 1
• No severe or uncontrolled renal condition

Cardiovascular

• No clinically significant acute electrocardiographic abnormalities
• LVEF normal by echocardiogram or MUGA within the past 12 months if there was prior exposure to anthracyclines
• No untreated or uncontrolled hypertension
  • No blood pressure > 150/100 mm Hg (despite treatment)
• No isolated systolic hypertension (i.e., systolic blood pressure > 180 mm Hg on at least 2 determinations [on separate days] within the past 3 months)
• No New York Heart Association class II - IV heart disease
• No active coronary artery disease requiring acute medical management
• No angina requiring acute medical management
• No congestive heart failure requiring acute medical management
• No ventricular arrhythmia requiring acute medical management
• No stroke or transient ischemic event within the past 6 months
• No prior or concurrent peripheral vascular disease
  • No angiographically or ultrasonographically documented arterial or venous occlusive event
  • No symptomatic claudication
• No symptomatic orthostatic hypotension
• No other severe or uncontrolled cardiovascular condition

Pulmonary

• No severe or uncontrolled pulmonary condition
• No pulmonary embolism within the past 6 months

Immunologic

• HIV negative
• No severe or uncontrolled immunologic condition
• No active current infection requiring antibiotics
• No prior hypersensitivity reaction to any recombinant proteins, including VEGF Trap

Other

• No severe or uncontrolled gastrointestinal or musculoskeletal condition
• No psychiatric condition or adverse social circumstance that would preclude study participation
• No other condition that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception during and for 3 months after study treatment

Expected Enrollment

A maximum of 25 patients will be accrued for this study.

Outline

This is an open-label, dose-escalation, multicenter study.

Patients receive VEGF Trap IV over 1 hour on days 1 and 15 for a total of 2 doses.

Cohorts of 3-6 patients receive escalating doses of VEGF Trap until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 6 patients are treated at that dose level.

In the absence of dose-limiting toxicity, patients with stable disease or partial or complete remission may continue to receive VEGF Trap on a separate extension protocol.

Patients are followed at weeks 1, 3, and 7 and then at 3 months.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

William Tew, MD, Principal investigator		Ph: 212-639-6555; 800-525-2225 Email: teww@mskcc.org

Registry Information
Official Title		An Open Label, Sequential Cohort Dose-Escalation Safety, Tolerability and Pharmacokinetic Study of VEGF Trap Administered Intravenously in Patients with Advanced Solid Tumors or Lymphoma
Trial Start Date		2004-01-13
Trial Completion Date		2010-01-13 (estimated)
Registered in ClinicalTrials.gov		NCT00083213
Date Submitted to PDQ		2004-03-03
Information Last Verified		2007-10-11
NCI Grant/Contract Number		CA08748

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