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

NCT00055237 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 03011003-C-0110
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kaposi's Sarcoma; HIV Infections; HIV Seronegativity

Keywords

Angiogenesis; Cancer; HHV-8; KSHV; Skin; Kaposi Sarcoma; KS

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Percentage of participants with a complete response (CR) + partial response (PR)per the Modified AIDS Clinical Trial Group Criteria (ACTG) for HIV-KS. PR is a 50% decrease in the number and/or size of previously existing lesions for 4 weeks; or complete flattening of at least 50% of all previously raised lesions lasting for at least 4 weeks; or a 50% decrease in the sum of the products of the largest perpendicular diameters of the marker lesions lasting for at least 4 weeks; CR is the absence of any detectable residual disease, including tumor associated edema, persisting for at least 4 weeks.

  36 months

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  70 months

Study Arms (2)

Cohort 1: Pts with HIV-associated Kaposi's Sarcoma

EXPERIMENTAL

15 mg/kg bevacizumab intravenously on days 1 and 8 then every 3 weeks.

Biological: Bevacizumab

Cohort 2: Pts with classic Kaposi's Sarcoma (HIV-uninfected)

EXPERIMENTAL

15 mg/kg bevacizumab intravenously on days 1 and 8 then every 3 weeks.

Biological: Bevacizumab

Interventions

Bevacizumab BIOLOGICAL

15 mg/kg day intravenously on day 1, day 8, then every 3 weeks.

Also known as: Avastin

Cohort 1: Pts with HIV-associated Kaposi's Sarcoma; Cohort 2: Pts with classic Kaposi's Sarcoma (HIV-uninfected)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (2)

• Uldrick TS, Wyvill KM, Kumar P, O'Mahony D, Bernstein W, Aleman K, Polizzotto MN, Steinberg SM, Pittaluga S, Marshall V, Whitby D, Little RF, Yarchoan R. Phase II study of bevacizumab in patients with HIV-associated Kaposi's sarcoma receiving antiretroviral therapy. J Clin Oncol. 2012 May 1;30(13):1476-83. doi: 10.1200/JCO.2011.39.6853. Epub 2012 Mar 19.

  PMID: 22430271 RESULT

• Uldrick T, Wyvill K, Kumar P, Bernstein W, O'Mahony D, Polizzotto M, Aleman K, Steinberg S, Pittaluga S, Little R, and Yarchoan R. A Phase II Study Targeting Vascular Endothelial Growth Factor with the Humanized Monoclonal Antibody Bevacizumab in the Treatment of Patients with HIV-Associated Kaposi Sarcoma. 17th Conference on Retroviruses and Opportunistic Infections. Oral Presentation. February 17, 2010.

  RESULT

MeSH Terms

Conditions

Sarcoma, Kaposi; HIV Infections; Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms, Vascular Tissue; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Robert Yarchoan, M.D.
• Organization: National Cancer Institute, National Institutes of Health

Robert.Yarchoan@nih.gov

301-496-0328

Study Officials

• Robert Yarchoan, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 21, 2003
• First Posted: February 21, 2003
• Study Start: February 26, 2003
• Primary Completion: March 15, 2010
• Study Completion: March 15, 2010
• Last Updated: September 6, 2017
• Results First Posted: July 26, 2012

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)