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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


Phase 1
25 Years
N/A
Not Enrolling
Both
Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Jakob Dupont, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

REGENERON-VGFT-ST-0103

NCT ID:

NCT00036946

Start Date:

November 2001

Completion Date:

Related Keywords:

  • Lymphoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic
  • Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021