Combination Therapy for Advanced Kaposi Sarcoma

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Name of the Trial

Pilot Study of Liposomal Doxorubicin Combined with Bevacizumab Followed by Bevacizumab Monotherapy in Adults with Advanced Kaposi Sarcoma (NCI-09-C-0130). See the protocol summary.

Principal Investigators

Dr. Robert Yarchoan and Dr. Thomas Uldrick (Lead Associate Investigator), NCI Center for Cancer Research

Dr. Robert Yarchoan and Dr. Thomas Uldrick
Drs. Robert Yarchoan and Thomas Uldrick

Why This Trial Is Important

Kaposi sarcoma (KS) is a rare type of cancer that produces tumors with abnormally dense and irregular blood vessels. These blood vessels leak red blood cells into the surrounding tissue, giving the tumors a characteristic dark appearance. KS tumors can form beneath the skin, in the mucous membranes of the mouth, nose, and throat, or along the gastrointestinal tract. The lymph nodes, lungs, and other organs may also be affected, especially in advanced cases.  There are several different types of KS that are defined by the populations they most commonly affect. KS is caused by a virus called Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8).

Patients with advanced KS are often treated with a drug called liposomal doxorubicin. Although many patients respond to this treatment, some require long-term therapy that may exceed the maximum cumulative dose recommended for this drug. In addition, liposomal doxorubicin belongs to a class of drugs called anthracyclines, which may decrease the number of critical CD4-positive T lymphocytes in patients with HIV-associated KS. Therefore, researchers are looking for targeted therapies for KS that may decrease the amount of liposomal doxorubicin administered, particularly the amount given over a patient’s lifetime.

Increased production of a protein called vascular endothelial growth factor (VEGF), which stimulates the formation of new blood vessels (angiogenesis), is thought to be one factor that contributes to the abnormal growth of blood vessels in KS tumors. Therefore, researchers have been interested in seeing whether KS might respond to bevacizumab, a monoclonal antibody that blocks angiogenesis by targeting VEGF.  In an earlier study conducted by NCI’s HIV and AIDS Malignancy Branch, bevacizumab showed promising activity against KS in patients with the classic and HIV-associated forms of the disease, especially in patients with certain manifestations of KS, such as pleural effusions and tumor-associated edema.  Now, these researchers want to see if combining bevacizumab with liposomal doxorubicin will be effective in shrinking KS tumors in patients with advanced disease.  

In this clinical trial, adult patients with any form of advanced KS will be treated with liposomal doxorubicin and bevacizumab every 3 weeks for a maximum of six treatments.  Patients who respond to this therapy or have stable disease will receive bevacizumab alone every 3 weeks for a maximum of 11 treatments. Doctors will evaluate the overall response rate, safety, and 12-month progression-free survival associated with this treatment regimen.

“The HIV and AIDS Malignancy Branch at NCI has been heavily involved in the development of effective therapies for KS for over 20 years.  As our knowledge about the biology of KSHV-related cancers improves, we continue to evaluate less toxic therapies for KS patients,” said Dr. Uldrick. “This is important because some patients may have a waxing and waning course with their disease and may need multiple treatments over their lifetimes, particularly given the aging of the HIV-infected population in the United States. One of our goals is to decrease the amount of cytotoxic chemotherapy that patients are exposed to over the course of their lifetime.

“The current study builds on our previous one of bevacizumab alone in KS,” he added. “We hope this combination will allow for the rapid treatment of advanced KS while being less toxic and requiring less anthracycline in the long-run than would otherwise be needed.” 

For More Information

See the lists of eligibility criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.