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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: ziv-aflibercept


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: ziv-aflibercept|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult Burkitt lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage IV mantle cell lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, stage IV small lymphocytic lymphoma, stage IV marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma