Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Bevacizumab in Treating Patients With Kaposi's Sarcoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	18 and over	NCI	NCI-03-C-0110 NCI-5513, 5513, NCT00058136

Special Category: NIH Clinical Center trial, NCI Web site featured trial

Objectives

1. Determine, preliminarily, the antitumor effect of bevacizumab in patients with classic or epidemic (AIDS-associated) Kaposi's sarcoma.
2. Determine the toxicity of this drug in these patients.
3. Determine, preliminarily, the progression-free survival of patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Histologically confirmed Kaposi's sarcoma (KS) by Center for Cancer Research (CCR)



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



• No symptomatic, extensive pulmonary involvement



• No symptomatic visceral KS, excluding the oral cavity

Prior/Concurrent Therapy:

Biologic therapy

• HIV-positive patients must be willing to comply with a regimen of highly active antiretroviral therapy (HAART) and meet 1 of the following criteria:
  • Be on a regimen of HAART selected for best potential efficacy for at least 1 month with evidence of KS progression on the regimen
  • Be on an optimized regimen of HAART for at least 4 months with no evidence of KS progression
• More than 30 days since prior IV immunoglobulin or monoclonal antibody therapy
• No prior bevacizumab
• No concurrent immunomodulatory agents
• No concurrent cytokines except epoetin alfa or filgrastim (G-CSF)

Chemotherapy

• More than 3 weeks since prior chemotherapy
• No concurrent cytotoxic chemotherapy for KS

Endocrine therapy

• More than 3 weeks since prior supraphysiologic doses of corticosteroids
• No concurrent systemic glucocorticoid steroids

Radiotherapy

• No concurrent radiotherapy for KS

Surgery

• More than 4 weeks since prior major surgery (including periodontal)

Other

• See Hepatic
• No prior SU5416 (semaxanib)
• No other concurrent anticoagulation therapy
• No concurrent chronic daily aspirin (325 mg or more per day) or nonsteroidal anti-inflammatory medication interfering with platelet function
• No concurrent IV antibiotics on day of study drug infusion
• No concurrent topical anti-KS medications
• No other concurrent therapies for KS

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 6 months

Hematopoietic

• WBC > 1,000/mm³
• Absolute neutrophil count > 750/mm³
• Platelet count > 75,000/mm³
• Hemoglobin > 9 g/dL
• No coagulopathy

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN) except for patients receiving protease inhibitor therapy known to be associated with increased bilirubin (e.g., indinavir, ritonavir, nelfinavir, or atazanavir); in this case, total bilirubin ≤ 7.5 mg/dL and the direct fraction ≤ 0.7 mg/dL
• AST/ALT ≤ 2.5 times ULN
• PT and PTT ≤ 120% of control (unless due to the presence of a lupus anticoagulant)
• INR ≤ 1.5

  OR

• INR 2-3 for patients receiving stable-dose warfarin or low molecular weight heparin AND no active bleeding or pathological conditions that carry a high risk of bleeding (tumor-involving major vessels)

Renal

• Creatinine ≤ 1.5 mg/dL

  OR

• Creatinine clearance ≥ 60 mL/min
• Urine protein < 1+

  OR

• 24-hour urine protein < 500 mg

Cardiovascular

• No history of deep vein or arterial thrombosis
• No clinically significant cardiovascular disease
• No clinically significant peripheral artery disease
• No cardiovascular accident within the past 6 months
• No transient ischemic attack within the past 6 months
• No uncontrolled hypertension (systolic blood pressure must be < 160 mm Hg and diastolic blood pressure < 95 mm Hg)
• No unstable angina
• No myocardial infarction
• No New York Heart Association grade II or greater congestive heart failure
• No cardiac arrhythmia requiring medication
• No grade II or greater peripheral vascular disease

Pulmonary

• See Disease Characteristics

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No substantial CNS disease, including the following:
  • History of CNS bleeding
  • Mass lesions of the brain
  • Uncontrolled seizure disorder
• No other prior or concurrent malignant tumors except completely resected basal cell skin cancer, in situ squamous cell carcinoma of the cervix or anus, or any other cancer in complete remission for at least 1 year
• No history of gastrointestinal bleeding
• No evidence of a severe or life-threatening infection within the past 2 weeks
• No concurrent condition requiring IV antibiotics
• No surgical or other nonhealing wound unrelated to KS
• No unstable bone fractures that are not stress/weight bearing able
• No other abnormality that would be scored as a grade 3 toxicity except for the following:
  • Lymphopenia
  • Direct manifestations of KS
  • Direct manifestations of HIV
  • Direct manifestations of HIV therapy (i.e., hyperbilirubinemia associated with protease inhibitors)
  • Asymptomatic hyperuricemia
• No known hypersensitivity to bevacizumab
• No known hypersensitivity to Chinese hamster ovary cell products
• No known hypersensitivity to other recombinant human or humanized antibodies
• No other condition that would preclude study participation

Expected Enrollment

A total of 8-27 patients will be accrued for this study within 1 year.

Outcomes

Antitumor effect by Kaposi's sarcoma (KS) response criteria in patients with HIV-associated KS

Antitumor effect by Kaposi's sarcoma (KS) response criteria in patients with classic KS
Toxicity profile by NCI CTC version 2.0 in patients with HIV-associated KS or classic KS
Progression-free survival
Response as measured by changes in SDF-1 expression
Changes in HHV-8 viral load in peripheral blood mononuclear cells
Changes in serum vascular endothelial growth factor (VEGF) levels
Changes in viral interleukin-6 levels

Outline

Patients receive a loading dose of bevacizumab IV over 90 minutes. Beginning 1 week later, patients receive bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed at 3 to 6 weeks.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Robert Yarchoan, MD, Protocol chair		Ph: 301-496-0328

U.S.A.
Maryland
	Bethesda
	NCI - HIV and AIDS Malignancy Branch
		Robert Yarchoan, MD	Ph:  301-496-8959
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Related Information

Web site for additional information
Featured trial article

Registry Information
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
Trial Start Date		2003-02-19
Trial Completion Date		2010-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00058136
Date Submitted to PDQ		2003-02-24
Information Last Verified		2008-11-30

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