Phase I and Pharmacokinetic Study of BAY 43-9006 (Sorafenib) in Patients With Kaposi's Sarcoma
Protocol # 06-C-0083
- Why is this trial important?
- Who is eligible for this trial?
- What types of drugs or therapies are being used?
- What is the study outline?
- What is the frequency and duration of the visits?
- What are the costs?
- Who is the Principal Investigator?
- Where is this trial taking place?
- Who are the contacts for this trial?
- Where can additional information be found?
Why is this trial important?
At the present time, systemic chemotherapy for Kaposi's sarcoma usually involves cytotoxic chemotherapy drugs that have short-term and cumulative toxicities. As a result, novel targeted therapies are urgently needed. This trial is exploring a novel targeted therapy that blocks several specific pathways believed to be important in the formation and growth of Kaposi's sarcoma. BAY 43-9006 (also called sorafenib) blocks both mutant and wild-type c-Raf kinase, which is important in the formation of many tumors. This drug was recently approved for patients with advanced kidney cancer, and there is thus substantial human experience with the agent. BAY 43-9006 blocks several receptors that appear to be particularly important in Kaposi's sarcoma, including a special form of the receptor for vascular endothelial growth factor (VEGF-R3).
Who is eligible for this trial? (PDQ)
- Histologically confirmed Kaposi's sarcoma (KS)
- HIV-related or HIV-unrelated (classic) KS
- Measurable disease, as defined by one of the following:
- At least 5 measurable cutaneous KS lesions that have not been previously treated with local therapy
- Other measurable noncutaneous disease that permit a response to be assessed
- Patients with HIV-related KS must be receiving and willing to comply with a highly active antiretroviral therapy (HAART) regimen that either utilizes ≥ 3 drugs OR attains suppression of HIV to below the limit of detection (50 copies HIV/mL)
- HIV-related KS lesions must meet one of the following criteria:
- Increasing during the 3 months prior to screening while the patient is receiving HAART or has unchanged suppression of HIV to below the limit of detection
- Stable for at least 4 months while the patient is taking HAART
- No extensive, active, or symptomatic pulmonary KS
- No symptomatic visceral KS, except for that involving the oral cavity
- No KS that appears to be improving after other therapy
- Hemoglobin > 9 g/dL ,WBC > 1,000/mm3, Platelet count > 75,000/mm3, PT and PTT ≤ 120% of control, unless lupus anticoagulant present
- Bilirubin ≤ 1.5 times upper limit of normal (ULN) (for patients not receiving protease inhibitor therapy) OR total bilirubin ≤ 3.7 mg/dL with a direct bilirubin fraction ≤ 0.2 mg/dL (for patients receiving protease inhibitor therapy), AST ≤ 2.5 times ULN
- Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
- Lipase ≤ 2 times ULN OR amylase ≤ 2 times ULN (unless documented to be of nonpancreatic origin or associated with macroamylasemia)
What types of drugs or therapies are being used?
BAY 43-9006
What is the study outline? (PDQ)
This is a dose-escalation, parallel group study.
- Patients are stratified according to concurrent ritonavir treatment (yes vs. no) and HIV-related Kaposi's sarcoma (KS) (yes vs. no)
- Patients receive oral sorafenib once or twice daily on Days 1 through 21
- Treatment repeats every 21 days for up to 18 courses (54 weeks) in the absence of disease progression or unacceptable toxicity
- Groups of 6 patients per stratum receive escalating doses of sorafenib until the maximum tolerated dose is determined
- After completion of study therapy, patients are followed for 3 to 6 weeks
What is the frequency and duration of the visits?
Patients will spend a full day at NIH for a screening appointment. Patients will spend 6 hours at NIH on the day they start treatment. Patients will need to be at NIH for 2 to 3 hours per week during the next 3 weeks. Patients will then be required to go to NIH every 3 weeks for a 2 to 3 hour visit.
What are the costs?
There is no charge for medical care received at the National Institutes of Health (NIH) Clinical Center. Patients will be responsible for travel costs for their initial screening visits. In most cases, once patients are enrolled in a trial, the National Cancer Institute (NCI) will pay the transportation costs for all subsequent trial-related visits for patients who do not live in the local area. In addition, these patients will receive a small per diem to help offset the costs of meals and lodging if they are being treated as outpatients.
It will be important to maintain your current insurance plan to cover all medical care that is provided away from the NIH Clinical Center.
No U.S. citizen or permanent U.S. resident residing in the U.S. who otherwise meets the eligibility requirements will be denied enrollment in clinical research protocols because of their inability to pay the costs of travel and subsistence.
Who is the Principal Investigator?
Dr. Robert Yarchoan received his B.A. from Amherst College with a major in biophysics and his M.D. from the University of Pennsylvania. He trained in internal medicine at the University of Minnesota and immunology in the Metabolism Branch, NCI. He then joined the laboratory of Dr. Samuel Broder, where he played a major role in the development of the first effective therapies for HIV infection, including zidovudine (AZT), didanosine (ddI), and zalcitabine (ddC). In particular, he led the first clinical trials of these drugs, was a co-inventor of didanosine and zalcitabine as AIDS therapies, and led initial studies of combination anti-HIV therapy. He was section chief in the Medicine Branch from 1991 to 1996 and was named chief of the newly formed HIV and AIDS Malignancy Branch in 1996. Since that time, he has focused much of his research on AIDS-related malignancies. Among other honors, he has been awarded the Assistant Secretary for Health Award and the U.S. Public Health Service Outstanding Service Medal, has been inducted as a Fellow of the American Association for the Advancement of Science, and is a member of the American Society for Clinical Investigation.
Where is this trial taking place?
NIH Clinical Center
National Institutes of Health
HIV and AIDS Malignancy Branch
10 Center Drive
Bethesda, Maryland 20892
Who are the contacts for this trial?
Robert Yarchoan, M.D.
Principal Investigator
Phone: 301-496-8959
yarchoan@helix.nih.gov
Thomas Uldrick, M.D.
Lead Associate Investigator
Phone: 301-496-8959
uldrickts@mail.nih.gov
Referrals:
Kathy Wyvill, R.N.
Research Nurse
Phone: 301-496-8959
1-800-243-2732 ext. 4 (Toll Free)
Fax: 301-402-7552
wyvillk@mail.nih.gov
Karen Aleman, R.N., B.S.N.
Research Nurse
Phone: 301-496-8959
1-800-243-2732 ext. 4 (Toll Free)
Fax: 301-402-7552
alemank@mail.nih.gov
Where can additional information be found?
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