Phase 2 N=19 Treatment

Bevacizumab to Treat Kaposi's Sarcoma in HIV-Positive and HIV-Negative Patients

Kaposi's Sarcoma · HIV Infections · HIV Seronegativity

Bottom Line

View on ClinicalTrials.gov: NCT00055237 ↗

Enrolled (actual)

Serious AEs

21.1%

Results posted

Jul 2012

Primary outcome: Primary: Response Rate — 31 Percentage of participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Bevacizumab (Biological)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: National Cancer Institute (NCI)
Primary completion: Mar 2010

Outcome Measures

Outcome	Result	p-value
PRIMARY Response Rate	31	—
SECONDARY Number of Participants With Adverse Events	19	—

Summary

This study will examine the safety and effectiveness of the experimental drug bevacizumab for treating both non-acquired immune deficiency syndrome (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 vascular endothelial growth factor (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 National Institutes of Health (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. * cluster of differentiation 4 (CD4) cell counts and human immunodeficiency virus (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 computed tomography (CT) or magnetic resonance imaging (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.

Eligibility Criteria

INCLUSION CRITERIA:

Age greater than or equal to 18 years.

Kaposi's sarcoma pathologically confirmed by Center for Cancer Research (CCR) pathology.

Eastern Cooperative Oncology Group (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;
White blood cell (WBC) greater than 1000/mm^3;
Absolute neutrophil count (ANC) greater than 750/mm^3;
Platelets greater than 75,000/mm^3;
Prothrombin time (PT) and partial thromboplastin time (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 upper limit of normal (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.

Aspartate aminotransferase (AST)/glutamic oxaloacetic transaminase (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: systolic blood pressure (SBP) less than 160 mm/Hg; diastolic blood pressure (DBP) less than 95 mm/Hg.

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

Patients with human immunodeficiency virus (HIV) infection must be willing to comply with a regimen of highly active antiretroviral therapy and be on a regimen of highly active antiretroviral therapy (HAART) selected for best potential efficacy for at least 1 month with evidence of Kaposi sarcoma (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 international normalized ratio (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 low molecular weight (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), unst

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Data sourced from ClinicalTrials.gov (NCT00055237). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.