Intravenous VEGF Trap in Treating Patients With Relapsed or Refractory Advanced 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 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.

Detailed Description
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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.

Official Title
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An Open Label, Sequential Cohort Dose-Escalation Safety, Tolerability and Pharmacokinetic Study of VEGF Trap Administered Intravenously in Patients With Advanced Solid Tumors or Lymphoma

Conditions
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Cancer

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 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

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


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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recurrent grade 1 follicular lymphoma, stage IV grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, stage IV grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, stage IV grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, recurrent adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, recurrent adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, unspecified adult solid tumor, protocol specific, recurrent adult soft tissue sarcoma, recurrent adult primary liver cancer, advanced adult primary liver cancer, recurrent cervical cancer, stage IVA cervical cancer, stage IVB cervical cancer, fallopian tube cancer, ovarian sarcoma, recurrent ovarian epithelial cancer, stage IV ovarian epithelial cancer, recurrent endometrial carcinoma, stage IV endometrial carcinoma, recurrent uterine sarcoma, stage IV uterine sarcoma, recurrent ovarian germ cell tumor, stage IV ovarian germ cell tumor, ovarian stromal cancer, recurrent vaginal cancer, stage IVA vaginal cancer, stage IVB vaginal cancer, recurrent prostate cancer, stage IV prostate cancer, recurrent penile cancer, stage IV penile cancer, recurrent malignant testicular germ cell tumor, stage III malignant testicular germ cell tumor, recurrent bladder cancer, stage IV bladder cancer, recurrent vulvar cancer, stage IVB vulvar cancer, distal urethral cancer, proximal urethral cancer, recurrent urethral cancer, urethral cancer associated with invasive bladder cancer, primary peritoneal cavity cancer, 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, stage IV adult soft tissue sarcoma