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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00036946
• Other study ID #: REGENERON-VGFT-ST-0103
• Secondary ID: MSKCC-01131CDR00
• Status: Completed
• Phase: Phase 1
• First received: May 13, 2002
• Last updated: June 1, 2016
• Start date: November 2001

Study information

• Verified date: June 2016
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: March 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years to 120 Years

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Biological:
• ziv-aflibercept

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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.

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.

Tew WP, Gordon M, Murren J, Dupont J, Pezzulli S, Aghajanian C, Sabbatini P, Mendelson D, Schwartz L, Gettinger S, Psyrri A, Cedarbaum JM, Spriggs DR. Phase 1 study of aflibercept administered subcutaneously to patients with advanced solid tumors. Clin Ca — View Citation