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

NCT ID: NCT00036946

Last Updated: 2016-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-11-30

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.

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.

Conditions

Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Primary Study Purpose: TREATMENT

Interventions

ziv-aflibercept

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jakob Dupont, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

References

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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 Cancer Res. 2010 Jan 1;16(1):358-66. doi: 10.1158/1078-0432.CCR-09-2103. Epub 2009 Dec 22.

Reference Type: RESULT

PMID: 20028764 (View on PubMed)

Other Identifiers

MSKCC-01131

Identifier Type: -

Identifier Source: secondary_id

CDR0000069343

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-G02-2065

Identifier Type: -

Identifier Source: secondary_id

REGENERON-VGFT-ST-0103

Identifier Type: -

Identifier Source: org_study_id