Kaposi Sarcoma (KS) is common in people with human immunodeficiency virus (HIV) but can also
occur in people who do not have HIV. KS tumors usually involve the skin, but may also involve
lymph nodes, lungs, bone, and gastrointestinal tract. Researchers want to see if a drug that
is currently used to treat a type of breast cancer can help.
To find a safe dose of abemaciclib to treat KS and to see if it can shrink lesions or tumors.
People ages 18 and older with KS.
Participants will be screened with some or all of the following:
Blood and urine tests
Chest x-ray and/or computed tomography scans
Lung or gastrointestinal tract exam with an endoscope (a flexible instrument to examine the
interior of the organ)
Heart function tests
KS lesion assessment
Skin sample from a KS lesion
Treatment will be given in 28-day cycles. Participants will take the study drug tablets by
mouth everyday. They will keep a medicine diary. They will get the study drug until their
cancer gets worse or they have unacceptable side effects.
Participants will have a study visit at the beginning of each cycle. At these visits, they
will repeat some screening tests. They may have medical photographs taken of body surfaces.
They may complete questionnaires about their quality of life. They may give skin and saliva
samples. For skin samples, an area of skin will be numbed. A small circle of skin over an
area affected by KS will be removed.
Participants will have follow-up visits for up to 2 years after treatment ends.
Kaposi Sarcoma (KS) is a multicentric angioproliferative tumor, caused by Kaposi
sarcoma-associated herpesvirus, that most frequently involves the skin, but may also
involve lymph nodes, lungs, bone and gastrointestinal tract. It is most common in people
with HIV but may also occur in patients without a diagnosis of HIV. Patients with
HIV-associated KS have worse survival than HIV-infected patients without KS.
As it is a relapsing and remitting condition, patients with KS often require prolonged
courses of cytotoxic chemotherapy and improved approaches for refractory and recurrent
KS are needed to decrease morbidity among patients with KS.
Cell cycle dysregulation is one of the hallmarks of cancer and has been developed as a
therapeutic target in patients with metastatic breast cancer. Cell cycle is controlled
by several proteins, including cyclin D kinases (CDKs), cyclins and retinoblastoma
(Rb)-E2F signaling pathway.
Abemaciclib is an orally available cyclin-dependent kinase (CDK) inhibitor that targets
the CDK4 (cyclin D1) and CDK6 (cyclin D3) cell cycle pathways thereby inhibiting
retinoblastoma (Rb) protein phosphorylation in early G1.
KS is an endothelial tumor, and KSHV-infected endothelial cells serve as the best
current model for KS as there are no good animal models for this disease. Abemaciclib
was found to inhibit proliferation of KSHV-infected and uninfected human umbilical vein
endothelial cells (HUVEC) at doses as low as 0.1 microM.
Published Phase I/II studies demonstrated that abemaciclib led to clinical responses in
patients with metastatic breast cancer and other tumor types, such as glioblastoma,
colorectal cancer, and melanoma.
Abemaciclib is a therapy licensed for use in metastatic breast cancer both as
monotherapy and in combination with other cancer therapies and the safety and efficacy
profiles of this agent are very well known. We hypothesize that abemaciclib will be
well-tolerated and patients with KS who have received prior therapies will derive some
-To evaluate the safety and tolerability of abemaciclib in participants with both untreated
and previously treated Kaposi sarcoma
Age >=18 years
Histologically confirmed Kaposi sarcoma (KS)
KS requiring systemic therapy, with either no prior systemic therapy or history of at
least 1 prior line of systemic therapy:
3 weeks from last chemotherapy
3 weeks from last immunotherapy
At least five measurable cutaneous KS lesions with no previous local radiation, surgical
or intralesional cytotoxic therapy to these measurable lesions.
ECOG Performance Status (PS) <= 2
Participant must be willing to give informed consent.
Participants can be HIV positive or negative.
Antiretroviral therapy (ART) for HIV+ participants
Participants receiving other investigational agents will not be eligible.
This is a phase I/II study assessing the safety and efficacy of abemaciclib in
participants with previously untreated or treated KS.
In the phase I portion of the study, up to 18 KS participants treated with prior therapy
will be enrolled in a 3+3 dose de-escalation schema using 2 dose de-escalation levels.
Following identification of an optimal dose and schedule, an expansion phase (Phase II)
will be initiated. Up to 25 previously untreated or treated KS participants will be
Abemaciclib will be administered as an oral planned starting dose of 200 mg twice daily
(in the morning and evening) without regard to meals. Abemaciclib will be given
continuously; one cycle equals 28 days.
Participants will receive therapy until optimal tumor response, unacceptable toxicity,
the participant s request to discontinue therapy, or PI decision. Participants with
disease progression will have the option of an additional 12 weeks of treatment, if the
PI feels that they are deriving clinical benefit.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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