Abemaciclib in Patients With HIV-associated and HIV-negative Kaposi Sarcoma

Kaposi Sarcoma Clinical Trial

Official title: A Phase I/II Study of Abemaciclib in Patients With HIV-associated and HIV-negative Kaposi Sarcoma

Status Recruiting

Clinical Trial Summary

Background:

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.

Objective:

To find a safe dose of abemaciclib to treat KS and to see if it can shrink lesions or tumors.

Eligibility:

People ages 18 and older with KS.

Design:

Participants will be screened with some or all of the following:

Medical history

Physical exam

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)

Medicine review

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.

Clinical Trial Description

Background:

• 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 clinical benefit.

Objectives:

-To evaluate the safety and tolerability of abemaciclib in participants with both untreated and previously treated Kaposi sarcoma

Eligibility:

• 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.

Design:

• 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 enrolled.

• 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. ;

Related Conditions & MeSH terms

• Kaposi Sarcoma
• Sarcoma
• Sarcoma, Kaposi

• NCT number: NCT04941274
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Anaida Widell
• Phone: (240) 760-6074
• Email: anaida.widell@nih.gov
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 29, 2021
• Completion date: June 1, 2028