- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00083213
Intravenous VEGF Trap in Treating Patients With Relapsed or Refractory Advanced Solid Tumors or Non-Hodgkin's Lymphoma
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
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.
Study Overview
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10021
- Memorial Sloan - Kettering Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: William P. Tew, MD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
General Publications
- Lockhart AC, Rothenberg ML, Dupont J, Cooper W, Chevalier P, Sternas L, Buzenet G, Koehler E, Sosman JA, Schwartz LH, Gultekin DH, Koutcher JA, Donnelly EF, Andal R, Dancy I, Spriggs DR, Tew WP. Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol. 2010 Jan 10;28(2):207-14. doi: 10.1200/JCO.2009.22.9237. Epub 2009 Nov 30.
- Wang-Gillam A, Tew WP, Rothenberg ML, Dupont J, Cooper W, Sternas L, Buzenet G, Sosman JA, Spriggs DR, Lockhart AC. A phase I study of subcutaneously administered aflibercept (VEGF trap) in a new formulation in patients with advanced solid tumors. Invest New Drugs. 2012 Oct;30(5):1958-61. doi: 10.1007/s10637-011-9753-y. Epub 2011 Oct 15.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- stage III malignant testicular germ cell tumor
- recurrent bladder cancer
- stage IV bladder cancer
- stage IV prostate cancer
- recurrent prostate cancer
- unspecified adult solid tumor, protocol specific
- stage IV ovarian epithelial cancer
- recurrent ovarian epithelial cancer
- fallopian tube cancer
- stage IV grade 3 follicular lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult Burkitt lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult Burkitt lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV mantle cell lymphoma
- primary peritoneal cavity cancer
- distal urethral cancer
- proximal urethral cancer
- recurrent urethral cancer
- urethral cancer associated with invasive bladder cancer
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular 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
- advanced adult primary liver cancer
- recurrent adult primary liver cancer
- stage IV endometrial carcinoma
- recurrent endometrial carcinoma
- recurrent adult lymphoblastic lymphoma
- recurrent mantle cell lymphoma
- stage IVA cervical cancer
- stage IV adult lymphoblastic lymphoma
- stage IV adult soft tissue sarcoma
- recurrent adult soft tissue sarcoma
- stage IV uterine sarcoma
- recurrent uterine sarcoma
- ovarian sarcoma
- recurrent cervical cancer
- stage IVB cervical cancer
- ovarian stromal cancer
- recurrent ovarian germ cell tumor
- stage IV ovarian germ cell tumor
- recurrent malignant testicular germ cell tumor
- recurrent vaginal cancer
- stage IVA vaginal cancer
- stage IVB vaginal cancer
- recurrent vulvar cancer
- recurrent penile cancer
- stage IV penile cancer
- stage IVB vulvar cancer
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma
- Physiological Effects of Drugs
- Antineoplastic Agents
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Aflibercept
Other Study ID Numbers
- REGENERON-VGFT-ST-0202
- MSKCC-03137
- CDR0000360856 (Registry Identifier: PDQ (Physician Data Query))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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