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

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00036946

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Study Details

Study Description

Brief Summary

RATIONALE: VEGF Trap may stop the growth of solid tumors or non-Hodgkin's lymphoma by stopping blood flow to the cancer.

PURPOSE: Phase I trial to study the effectiveness of VEGF Trap in patients who have relapsed or refractory solid tumors or non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Unspecified Adult Solid Tumor, Protocol Specific	Biological: ziv-aflibercept	Phase 1

Detailed Description

OBJECTIVES:

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

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.

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

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

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

Study Start Date :

Nov 1, 2001

Actual Primary Completion Date :

Mar 1, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

PATIENT CHARACTERISTICS:

Age:

25 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3,500/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
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

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