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Bevacizumab to Treat Kaposi's Sarcoma in HIV-Positive and HIV-Negative Patients
This study has been completed.

First Received on February 21, 2003.   Last Updated on October 15, 2011   History of Changes
Sponsor: National Cancer Institute (NCI)
Information provided by: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00055237
  Purpose

This study will examine the safety and effectiveness of the experimental drug bevacizumab for treating both non-AIDS and AIDS-associated Kaposi's sarcoma (KS). KS tumors depend on the formation of new blood vessels for their growth. Bevacizumab is an antibody to a protein called VEGF that is produced by the body and is involved in blood vessel growth. Bevacizumab may block the action of VEGF, and thus help shrink KS lesions.

Patients 18 years of age and older with Kaposi's sarcoma that is restricted to the skin and is not life threatening may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), chest x-ray, and, if needed, imaging studies to evaluate internal tumors.

Participants will receive bevacizumab intravenously (by vein) once a week for 2 weeks and then every 3 weeks at the NIH Clinical Center. The first infusion takes about 90 minutes, the second takes about 60 minutes, and subsequent infusions take about 30 minutes. Infusions may take longer, however, if the drug is better tolerated at a slower infusion rate. Patients will be evaluated with the following tests and procedures:

  • Physical examination, assessment of drug side effects, measurement of KS lesions, and photographs of lesions once a week for the first 6 weeks of therapy, and then every 3 weeks.
  • CD4 cell counts and HIV viral load in HIV-positive patients every 12 weeks.
  • Biopsies of lesions: upon entering the study, at week 12, and at the time of a response of the tumor to therapy or at the end of treatment, if treatment ends at week 18 or later.
  • Additional biopsies, if requested. (Additional biopsies are not required.)
  • Other procedures, such as CT or MRI scans, if medically indicated.

Patients may continue bevacizumab therapy indefinitely if they are benefiting from it, as long as they have no substantial toxicity or other conditions that would cause them to stop receiving it and the protocol remains open.

...


Condition Intervention Phase
Kaposi's Sarcoma
HIV Infections
HIV Seronegativity
Biological: Bevacizumab
Phase II

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Intravenous Recombinant Humanized Anti-Vascular Endothelial Cell Growth Factor Antibody (Bevacizumab) in Classical (HIV-Negative) and in AIDS-Associated Kaposi's Sarcoma

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Antitumor effect by Kaposi's sarcoma (KS) response criteria in patients with HIV-associated KS [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity profile by NCI CTC version 2.0 in patients with HIV-associated KS or classic KS [ Designated as safety issue: Yes ]
  • Antitumor effect by Kaposi's sarcoma (KS) response criteria in patients with classic KS [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Response as measured by changes in SDF-1 expression [ Designated as safety issue: No ]
  • Changes in HHV-8 viral load in peripheral blood mononuclear cells [ Designated as safety issue: No ]
  • Changes in serum vascular endothelial growth factor (VEGF) levels [ Designated as safety issue: No ]
  • Changes in viral interleukin-6 levels [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: February 2003
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: Bevacizumab
    N/A
Detailed Description:

BACKGROUND:

This is a phase II study to determine the activity of bevacizumab, a putative antiangiogenic agent, in Kaposi's sarcoma (KS). Bevacizumab is a humanized recombinant antibody to vascular endothelial cell growth factor (VEGF), an important cytokine in the pathogenesis of KS.

OBJECTIVES:

To assess the antitumor effect of bevacizumab15 mg/kg administered intravenously once every three weeks in patients with HIV-associated KS. Other objectives include assessment of the antitumor effect of bevacizumab 15 mg/kg administered intravenously once every three weeks in patients with classical KS; assessment of the toxicity profile of bevacizumab in HIV-infected and HIV-negative patients with KS; exploration in a preliminary fashion effect of bevacizumab on KS progression free survival; and study of a number of biochemical parameters, including SDF-1 expression in KS lesions; HHV-8 viral load in peripheral blood mononuclear cells; serum VEFG levels over the course of treatment; and changes in viral IL-6 levels over the course of treatment.

ELIGIBILITY:

Key eligibility parameters include HIV-associated or classical Kaposi's sarcoma, age greater than or equal to 18 years, and life expectancy greater than 6 months. Patients with HIV infection must have either KS progression on a regimen of highly active antiretroviral therapy (HAART) for at least one month, or no KS regression while on an optimized regimen of HAART for 4 months or longer.

DESIGN:

Patients will be sequentially enrolled, administered a loading dose of 15 mg/kg bevacizumab intravenously on day 1, and then administered 15 mg/kg bevacizumab intravenously every 3 weeks beginning one week after the loading dose. The drug will be temporarily discontinued for toxicity, intercurrent major surgical procedures, or other factors that would pose a safety concern. Patients will undergo a biopsy of a KS lesion at entry, on cycle 4, day 21, and at the time of a formal response or when the patient stops treatment. Patients will undergo a number of other tests as well, including blood tests and non-invasive imaging studies of KS lesions.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Age greater than or equal to 18 years.

Kaposi's sarcoma pathologically confirmed by CCR pathology.

ECOG performance status less than or equal to 2.

Life expectancy greater than 6 months.

The following hematologic parameters:

  • Hemoglobin greater than 9 g/dl;
  • WBC greater than 1000/mm(3);
  • ANC greater than 750/mm(3);
  • Platelets greater than 75,000/mm(3);
  • PT and PTT less than or equal to 120% of control, unless patient has the presence of a lupus anticoagulant.

The following hepatic parameters:

Bilirubin less than or equal to 1.5 times the ULN unless the patient is receiving protease inhibitor therapy known to be associated with increased bilirubin: in this case total bilirubin less than or equal to 7.5 mg/dl and the direct fraction less than or equal to 0.7 mg/dl.

-Examples of protease inhibitors known to increase bilirubin levels include indinavir, ritonavir, nelfinavir, and atazanavir.

AST/GOT less than or equal to 2.5 times the upper limit of normal.

Either Serum creatinine less than or equal to 1.5 mg/dL or measured creatinine clearance greater than or equal to 60 mL/min.

Either Urine protein less than 1+ or measured 24 hour urine protein less than 500 milligram.

Blood pressure: SBP less than 160 mm/Hg; DBP less than 95 mm/Hg.

At least 5 assessable cutaneous lesions previously untreated by local therapy.

Patients with HIV infection must be willing to comply with a regimen of highly active antiretroviral therapy and be on a regimen of HAART selected for best potential efficacy for at least 1 month with evidence of KS progression on the HAART regimen or be on a optimized regimen of HAART for 4 months or longer with no evidence of KS regression.

Patients must be willing to use effective birth control.

EXCLUSION CRITERIA:

Symptomatic, extensive pulmonary involvement.

Symptomatic visceral KS excluding the oral cavity.

Inability to provide informed consent.

Chemotherapy within 3 weeks.

Prior therapy with SU5416.

Supraphysiologic doses of corticosteroids within 3 weeks.

Major surgical procedure (including periodontal) within 4 weeks.

Surgical or other non-healing wounds unrelated to KS.

Pregnancy.

Breast feeding.

Past or present history of malignant tumors other than KS unless: a) in a complete remission for greater than or equal to 1 year from the time a response was first documented; b) completely resected basal cell carcinoma; or c) in situ squamous cell carcinoma of the cervix or anus.

Evidence of a severe or life-threatening infection within 2 weeks of entry onto the study.

A condition that would require the patient to receive intravenous antibiotics on a day of bevacizumab infusion.

Need for chronic daily aspirin greater than or equal to 325 mg/daily or nonsteroidal medication interfering with platelet function.

Therapeutic anticoagulation with INR greater than 1.5, unless the patient is on full dose warfarin. If a patient is on full-dose anticoagulants, the following criteria should be met for enrollment:

The subject must have an in-range INR (usually between 2 and 3) on a stable dose of warfarin or on stable dose of LMW heparin;

The subject must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels).

History of deep venous or arterial thrombosis.

History of gastrointestinal bleeding.

Clinically significant cardiovascular disease such as uncontrolled hypertension (with systolic BP greater than 160 mm/Hg or diastolic blood pressure greater than 95 mm/Hg), unstable angina, New York Heart Association grade II or greater congestive heart failure, cardiac arrhythmia requiring medication, clinically significant peripheral artery disease, grade II or greater peripheral vascular disease, myocardial infarction.

Substantial CNS disease including history of CNS bleeding, mass lesions in the brain, uncontrolled seizure disorder, recent history of CVA (e.g. within the past 6 months), history of transient ischemic attack (TIA) within the past 6 months..

Coagulopathy.

Patients with unstable bone fractures that are not stress/weight bearing able.

Patients with any other abnormality that would be scored as a grade 3 toxicity, except lymphopenia, direct manifestations of KS, direct manifestation of HIV, direct manifestation of HIV therapy, hyperbilirubinemia associated with protease inhibitors, asymptomatic hyperuricemia.

Previous IVIG or monoclonal antibody therapy within 30 days prior to enrollment.

Known hypersensitivity to bevacizumab.

Known hypersensitivity to Chinese hamster ovary cell products.

Known hypersensitivity to other recombinant human or humanized antibodies.

Previous bevacizumab.

Any condition that, in the opinion of the Principal Investigator or Study Chairperson, would preclude the inclusion of a patient onto this research study.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00055237

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Additional Information:
Publications:
Responsible Party: Robert Yarchoan, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00055237     History of Changes
Obsolete Identifiers: NCT00058136
Other Study ID Numbers: 030110, 03-C-0110
Study First Received: February 21, 2003
Last Updated: October 15, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Angiogenesis
Cancer
HHV-8
KSHV
Skin
Kaposi Sarcoma
KS

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Sarcoma, Kaposi
Sarcoma
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Herpesviridae Infections
DNA Virus Infections
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012