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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00055237
• Date of registration: 21/02/2003
• Primary sponsor: National Cancer Institute (NCI)
• Public title: Bevacizumab to Treat Kaposi's Sarcoma in HIV-Positive and HIV-Negative Patients
• Scientific 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
• Date of first enrolment: February 2003
• Target sample size: 19
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00055237
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Robert Yarchoan, M.D.
• Affiliation: National Cancer Institute, National Institutes of Health

Key inclusion & exclusion 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),
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 central nervous system (CNS) disease including history of CNS bleeding, mass
lesions in the brain, uncontrolled seizure disorder, recent history of cerebrovascular
accident (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 intravenous immunoglobulin (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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

HIV Infections

HIV Seronegativity

Kaposi's Sarcoma

Intervention(s)

Biological: Bevacizumab

Primary Outcome(s)

Response Rate [Time Frame: 36 months]

Secondary Outcome(s)

Number of Participants With Adverse Events [Time Frame: 70 months]

Secondary ID(s)

03-C-0110

030110

Source(s) of Monetary Support

Please refer to primary and secondary sponsors