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

Regeneron Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Cancer

Treatments

Biological: ziv-aflibercept

Study type

Interventional

Funder types

Industry

NIH

Identifiers

NCT00083213

CDR0000360856 (Registry Identifier)

MSKCC-03137

REGENERON-VGFT-ST-0202

Details and patient eligibility

About

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

PURPOSE: This phase I trial is studying the side effects and best dose of intravenous VEGF Trap in treating patients with relapsed or refractory advanced solid tumors or non-Hodgkin's lymphoma.

Full description

OBJECTIVES:

Primary

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

Secondary

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

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.

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

Enrollment

25 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

Not specified

Hematopoietic

WBC ≥ 3,500/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Hemoglobin ≥ 9.0 g/dL
Platelet count ≥ 100,000/mm^3
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

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