- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00036946
VEGF Trap in Treating Patients With Relapsed or Refractory Solid Tumors or Non-Hodgkin's Lymphoma
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
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.
Studieoversigt
Status
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
New York
-
New York, New York, Forenede Stater, 10021
- Memorial Sloan-Kettering Cancer Center
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Studiestol: Jakob Dupont, MD, Memorial Sloan Kettering Cancer Center
Publikationer og nyttige links
Generelle publikationer
- 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.
- 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.
- 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.
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
- uspecificeret voksen solid tumor, protokol specifik
- stadium IV grad 3 follikulært lymfom
- stadium IV voksent diffust storcellet lymfom
- stadium IV voksen immunoblastisk storcellet lymfom
- stadium IV voksen Burkitt lymfom
- tilbagevendende grad 3 follikulært lymfom
- tilbagevendende voksent diffust storcellet lymfom
- tilbagevendende voksen immunoblastisk storcellet lymfom
- recidiverende voksen Burkitt lymfom
- recidiverende voksent diffust små spaltet celle lymfom
- recidiverende voksent diffust blandet celle lymfom
- stadium IV grad 1 follikulært lymfom
- stadium IV grad 2 follikulært lymfom
- stadium IV voksent diffust små spaltet celle lymfom
- stadium IV voksent diffust blandet celle lymfom
- stadium IV mantelcellelymfom
- tilbagevendende grad 1 follikulært lymfom
- tilbagevendende grad 2 follikulært lymfom
- tilbagevendende marginal zone lymfom
- tilbagevendende lille lymfocytisk lymfom
- stadium IV lille lymfocytisk lymfom
- stadium IV marginal zone lymfom
- ekstranodal marginal zone B-celle lymfom af slimhinde-associeret lymfoid væv
- nodal marginal zone B-celle lymfom
- milt marginal zone lymfom
- tilbagevendende lymfoblastisk lymfom hos voksne
- tilbagevendende kappecellelymfom
- stadium IV voksen lymfoblastisk lymfom
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- REGENERON-VGFT-ST-0103
- MSKCC-01131
- CDR0000069343 (Registry Identifier: PDQ (Physician Data Query))
- NCI-G02-2065
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