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LymphomaPhase 1NCT00036946

VEGF Trap in Treating Patients With Relapsed or Refractory Solid Tumors or Non-Hodgkin's Lymphoma

A Phase 1 study testing ziv-aflibercept in people with Lymphoma and Unspecified Adult Solid Tumor, Protocol Specific, run by Regeneron Pharmaceuticals at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 25 to 120 years
What is being tested?
ziv-aflibercept
How many people
Not given
Where
1 siteUnited States
Study dates
Nov 2001to Mar 2002
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

Other trials in United States

About this study

Official title: 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.

Read the detailed description

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.

Being tested
ziv-aflibercept
Keywords
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
Medical subject headings
Lymphoma, Lymphoma, Follicular, Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ziv-afliberceptBiological

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startNov 2001
  3. Primary completionMar 2002

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
IDs, dates and publications
ClinicalTrials.gov ID
NCT00036946
Sponsor's protocol ID
REGENERON-VGFT-ST-0103
Other IDs
MSKCC-01131, CDR0000069343, NCI-G02-2065
Status last verified
Jun 2016
First submitted
13 May 2002
Last updated
3 Jun 2016
Results posted
No

Publications

  • 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.

  • 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.

    PubMed 20028764
  • Wazan LE, Widhibrata A, Liu GS. Soluble FLT-1 in angiogenesis: pathophysiological roles and therapeutic implications. Angiogenesis. 2024 Nov;27(4):641-661. doi: 10.1007/s10456-024-09942-8. Epub 2024 Aug 29.

    PubMed 39207600

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ziv-aflibercept in people with Lymphoma and Unspecified Adult Solid Tumor, Protocol Specific, run by Regeneron Pharmaceuticals at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00036946, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2016.

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