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

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 25 and over NCI, Pharmaceutical / Industry MSKCC-01131 REGENERON-VGFT-ST-0103, NCI-G02-2065, NCT00036946

Objectives

1. Determine the safety and tolerability of VEGF Trap in patients with incurable relapsed or refractory solid tumors or non-Hodgkin's lymphoma.
2. Determine the maximum tolerated dose of this drug in these patients.
3. Determine the pharmacokinetics of this drug in these patients.
4. Evaluate the ability of this drug to bind and inactivate circulating vascular endothelial growth factor (VEGF) in these patients.
5. Determine the dosing regimen that is optimal for neutralization of circulating VEGF in these patients.
6. Determine whether antibodies to this drug develop in these patients.
7. Assess, preliminarily, the ability of this drug to alter tumor vascular permeability and tumor growth in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed incurable primary or metastatic solid tumor or non-Hodgkin's lymphoma
  • Relapsed after or is refractory (e.g., unresectable) to at least 2 standard chemotherapy regimens and rituximab
  • No standard curative surgery, chemotherapy, immunotherapy, other antitumor therapy, or radiotherapy options exist



• No known or suspected squamous cell carcinoma of the lung



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



• No prior or concurrent primary intracranial tumor by MRI or CT scan

Prior/Concurrent Therapy:

Biologic therapy:

• See Disease Characteristics
• At least 3 weeks since prior immunotherapy
• No concurrent epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF)

Chemotherapy:

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

Endocrine therapy:

• No concurrent adrenal corticosteroids, except low doses as replacement therapy in patients who have previously received suppressive doses or for adrenal insufficiency
• No concurrent systemic hormonal contraceptive agents

Radiotherapy:

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy

Surgery:

• See Disease Characteristics
• At least 3 weeks since prior surgery (except fine needle biopsy/aspiration or removal/biopsy of a skin lesion)
• No prior surgical procedure for correction or prophylaxis of peripheral vascular insufficiency or cerebral ischemic events

Other:

• Recovered from prior therapy
• At least 6 months since prior treatment for acute congestive heart failure
• At least 30 days since prior investigational drugs
• No concurrent standard or other investigational anticancer agents
• No concurrent herbal supplements ("nutraceuticals")
• No concurrent anticoagulant or antiplatelet drugs, (e.g., warfarin, heparin, aspirin, or other non-steroidal anti-inflammatory drugs) except selective cyclo-oxygenase-2 (COX-2) inhibitors for analgesia
• No concurrent COX-2 inhibitors for tumor treatment or prophylaxis

Patient Characteristics:

Age:

• 25 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2 times ULN
• Alkaline phosphatase no greater than 2 times ULN
• PT, PTT, and INR normal

Renal:

• Creatinine no greater than ULN
• No 1+ or greater proteinuria
• No other severe or uncontrolled renal condition

Cardiovascular:

• Electrocardiogram normal
• LVEF normal by echocardiogram or MUGA scan within the past 12 months or since completion of prior anthracycline
• No severe or uncontrolled cardiovascular condition
• No New York Heart Association class III or IV heart disease
• No active coronary artery disease, angina, congestive heart failure, or arrhythmia
• No myocardial infarction within the past 6 months
• No prior or concurrent peripheral vascular disease, including:
  • Angiographically or ultrasonographically documented arterial or venous occlusive event
  • Symptomatic claudication
• No untreated or uncontrolled hypertension
• No treated blood pressure more than 160/100 mm Hg on at least 3 repeated determinations on separate days within the past 6 weeks
• No symptomatic orthostatic hypotension

Pulmonary:

• No severe or uncontrolled pulmonary condition
• No pulmonary embolism

Other:

• No prior hypersensitivity reactions to any recombinant proteins (e.g., VEGF Trap)
• No severe or uncontrolled gastrointestinal, immunological, or musculoskeletal condition
• No severe or uncontrolled psychiatric or adverse social circumstance that would preclude study
• No active infection requiring antibiotics
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception during and for at least 3 months after study

Expected Enrollment

A maximum of 30 patients will be accrued for this study.

Outline

This is a dose-escalation study.

Patients receive VEGF Trap subcutaneously once daily on days 1, 29, 36, 43, 50, 57, and 64 in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 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, 5 additional patients are treated at the MTD.

Patients are followed at 1 and 4 weeks.

Dupont J, Schwartz L, Koutcher J, et al.: Phase I and pharmacokinetic study of VEGF Trap administered subcutaneously (sc) to patients (pts) with advanced solid malignancies. [Abstract] J Clin Oncol 22 (Suppl 14): A-3009, 197s, 2004.

Dupont J, Camastra D, Gordon MS, et al.: Phase 1 study of VEGF Trap in patients with solid tumors and lymphoma. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-776, 2003.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Jakob Dupont, MD, Protocol chair		Ph: 212-639-8984; 800-525-2225 Email: dupontj@mskcc.org

Registry Information
Official Title		An Open-Label, Sequential Cohort Dose-Escalation Safety, Tolerability And Pharmacokinetic Study Of VEGF Trap In Patients With Incurable, Relapsed Or Refractory Solid Tumors Or Lymphoma
Trial Start Date		2001-11-13
Registered in ClinicalTrials.gov		NCT00036946
Date Submitted to PDQ		2002-03-22
Information Last Verified		2005-04-06
NCI Grant/Contract Number		P30-CA08748

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