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.
調査の概要
詳細な説明
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.
研究の種類
段階
- フェーズ 1
連絡先と場所
研究場所
-
-
New York
-
New York、New York、アメリカ、10021
- Memorial Sloan-Kettering Cancer Center
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
協力者と研究者
捜査官
- スタディチェア:Jakob Dupont, MD、Memorial Sloan Kettering Cancer Center
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
- 詳細不明の成人固形腫瘍、プロトコル固有
- ステージ IV グレード 3 濾胞性リンパ腫
- IV期成人びまん性大細胞型リンパ腫
- ステージ IV の成人免疫芽球性大細胞型リンパ腫
- IV期の成人バーキットリンパ腫
- 再発性グレード 3 濾胞性リンパ腫
- 再発性成人びまん性大細胞型リンパ腫
- 再発性成人免疫芽細胞性大細胞型リンパ腫
- 再発成人バーキットリンパ腫
- 再発性成人びまん性小細胞分裂型リンパ腫
- 再発性成人びまん性混合細胞リンパ腫
- ステージ IV グレード 1 濾胞性リンパ腫
- ステージ IV グレード 2 濾胞性リンパ腫
- ステージ IV の成人びまん性小細胞分裂型リンパ腫
- IV期成人びまん性混合細胞リンパ腫
- IV期マントル細胞リンパ腫
- 再発性グレード 1 濾胞性リンパ腫
- 再発性グレード 2 濾胞性リンパ腫
- 再発辺縁帯リンパ腫
- 再発小リンパ球性リンパ腫
- IV期小リンパ球性リンパ腫
- ステージ IV 辺縁帯リンパ腫
- 節外性辺縁帯 粘膜関連リンパ組織の B 細胞性リンパ腫
- リンパ節辺縁帯B細胞リンパ腫
- 脾辺縁帯リンパ腫
- 再発性成人リンパ芽球性リンパ腫
- 再発性マントル細胞リンパ腫
- IV期成人リンパ芽球性リンパ腫
追加の関連 MeSH 用語
その他の研究ID番号
- REGENERON-VGFT-ST-0103
- MSKCC-01131
- CDR0000069343 (レジストリ識別子:PDQ (Physician Data Query))
- NCI-G02-2065
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。