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

NCT04941274 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 21002621-C-0026
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kaposi Sarcoma

Keywords

Angiogenesis; AIDS; cyclin-dependent kinase; KSHV; Cell Cycle

Outcome Measures

Primary Outcomes (2)

• safety and tolerability of abemaciclib

  The fraction of patients with toxicity noted at each dose level will be reported by grade and type of toxicity identified.

  28 days

• overall response rate

  Percentage of patients with the best overall response of CR or PR to therapy

  every 3 cycles until completion of therapy, then every 3 months for 6 months, then every 6 months for 2 years, then annually for 2 years

Secondary Outcomes (3)

• KS response to abemaciclib

  every 3 cycles from cycle 2 until completion of therapy, then every 3 months for 6 months, then every 6 months for 2 years, then annually for 2 years

• duration of response

  every 3 cycles until completion of therapy, then every 3 months for 6 months, then every 6 months for 2 years, then annually for 2 years

• Progression free survival

  every 3 cycles until completion of therapy, then every 3 months for 6 months, then every 6 months for 2 years, then annually for 2 years

Study Arms (3)

1/Dose Determination/De-Escalation

EXPERIMENTAL

Abemaciclib (de-escalating dose)

Drug: Abemaciclib

2/Dose Expansion: Group 2a

EXPERIMENTAL

Abemaciclib (at optimal dose determined in dose escalation portion of the study) for up to 15 participants previously treated with at least 1 line of systemic therapy.

Drug: Abemaciclib

2/Dose Expansion: Group 2b

EXPERIMENTAL

Abemaciclib (at optimal dose determined in dose escalation portion of the study) for up to 10 previously untreated participants.

Drug: Abemaciclib

Interventions

Abemaciclib DRUG

An initial dose of 200 mg twice daily and at an MTD dose will be administered orally every day of each 28-day cycle.

1/Dose Determination/De-Escalation; 2/Dose Expansion: Group 2a; 2/Dose Expansion: Group 2b

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have Kaposi sarcoma confirmed by the Laboratory of Pathology, NCI
• Measurable disease as follows:
• All participants in Groups 1, 2a, or 2b should have at least five measurable cutaneous KS lesions per AIDS Clinical Trials Group Oncology Committee (ACTG) criteria with no previous local radiation, surgical or intralesional cytotoxic therapy that would prevent response assessment for that lesion.
• Measurable disease by the criteria proposed by the AIDS Clinical Trials Group Oncology Committee.
• Participants in Group 3 must have Stage T1 KS with at least five measurable cutaneous KS lesions per ACTG criteria and/or evaluable disease per RECIST criteria.
• Participants may be HIV positive or negative.
• Participants must be able to swallow oral medications
• For all groups, participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count \>1,000/mcL
• Platelets \>75,000/mcL
• Hemoglobin \>= 8gm/dL
• Total bilirubin \<= 1.5 upper limit of normal unless the participant is receiving a protease inhibitor known to be associated with increased bilirubin (e.g. atazanavir), in which case total bilirubin \<= 7.5 mg/dL with direct fraction \<= 0.7
• AST/ALT \<3 X institutional upper limit of normal
• Creatinine within normal institutional limits OR
• Creatinine clearance \>45 mL/min/1.73 m\^2 as estimated by either Cockroft-Gault or 24-hour urine collection for participants with creatinine levels above institutional normal

You may not qualify if:

• Participants who have had chemotherapy or immunotherapy within 3 weeks prior to entering the study.
• Participants who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and enrollment.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia or neuropathy.
• Participants who are receiving any other investigational agents.
• History of severe allergic reactions attributed to compounds of similar chemical or biologic composition to CDK inhibitor.
• Participants receiving any medications or substances that are strong/moderate inhibitors of CYP3A4 are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• Serious and/or uncontrolled severe intercurrent illness that in the judgement of the investigator would preclude participation in the study.
• No active KSHV-associated multicentric Castleman disease, KSHV-associated inflammatory cytokine syndrome or primary effusion lymphoma.
• Psychiatric illness/social situations that would limit adherence with study requirements.
• Pregnancy
• Prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the regimen are eligible for this trial
• Participants with interstitial lung disease

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma, Kaposi; Acquired Immunodeficiency Syndrome

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Ramya M Ramaswami, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anaida Widell

CONTACT

(240) 760-6074; anaida.widell@nih.gov

Ramya M Ramaswami, M.D.

CONTACT

(240) 506-1088; ramya.ramaswami@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2021
• First Posted: June 28, 2021
• Study Start: September 29, 2021
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: January 23, 2026

Record last verified: 2026-01-20

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@Requests for all collected IPD data from clinical trials, conducted under a binding collaborative agreement between NCI/DCTD and a pharmaceutical/biotechnology company, that are not under DSMB monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI/DCTD and the Pharmaceutical Collaborator (i.e., the NCI ETCTN Director in conjunction with the NCI/DCTD Regulatory Affairs Branch)

Locations

US (1)