|Phase II||Treatment||Completed||18 and over||NCI||030110|
03-C-0110, NCI-03-C-0110, NCI-5513, 5513, NCT00058136, NCT00055237
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.
Further Study Information
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.
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.
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.
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.
- 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.
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.
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..
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.
Any condition that, in the opinion of the Principal Investigator or Study Chairperson, would preclude the inclusion of a patient onto this research study.
Trial Lead Organizations/Sponsors
National Cancer Institute
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00055237
Information obtained from ClinicalTrials.gov on July 25, 2010
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