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

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ClinicalTrials.gov Identifier: NCT04941274
Recruitment Status : Recruiting
First Posted : June 28, 2021
Last Update Posted : November 5, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

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.


Condition or disease Intervention/treatment Phase
Kaposi Sarcoma Drug: Abemaciclib Phase 1 Phase 2

Show Show detailed description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Abemaciclib in Patients With HIV-associated and HIV-negative Kaposi Sarcoma
Actual Study Start Date : September 29, 2021
Estimated Primary Completion Date : March 1, 2028
Estimated Study Completion Date : June 1, 2028


Arm Intervention/treatment
Experimental: 1/Dose Determination/De-Escalation
Abemaciclib (de-escalating dose)
Drug: Abemaciclib
An initial dose of 200 mg twice daily and at an MTD dose will be administered orally every day of each 28-day cycle.

Experimental: 2/Dose Expansion: Group 2a
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
An initial dose of 200 mg twice daily and at an MTD dose will be administered orally every day of each 28-day cycle.

Experimental: 2/Dose Expansion: Group 2b
Abemaciclib (at optimal dose determined in dose escalation portion of the study) for up to 10 previously untreated participants.
Drug: Abemaciclib
An initial dose of 200 mg twice daily and at an MTD dose will be administered orally every day of each 28-day cycle.




Primary Outcome Measures :
  1. safety and tolerability of abemaciclib [ Time Frame: 28 days ]
    The fraction of patients with toxicity noted at each dose level will be reported by grade and type of toxicity identified.

  2. overall response rate [ Time Frame: 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 ]
    Percentage of patients with the best overall response of CR or PR to therapy


Secondary Outcome Measures :
  1. KS response to abemaciclib [ Time Frame: 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 ]
    Staging and response to abemaciclib for KS by the evaluation of number, size, nodularity, and color of lesions.

  2. duration of response [ Time Frame: 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 ]
    The time criteria are met for CR or PR (whichever is recorded first) until the first date that patient no longer qualifies as a PR

  3. Progression free survival [ Time Frame: 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 ]
    Duration of time from the start of the treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Participants must have Kaposi sarcoma confirmed by the Laboratory of Pathology, NCI
  • All participants should have at least five measurable cutaneous KS lesions 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 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(SGOT)/ALT(SGPT) <3 X institutional upper limit of normal
    • Creatinine within normal institutional limits OR
    • Creatinine clearance >45 mL/min/1.73 m2 as estimated by either Cockroft-Gault or 24-hour urine collection for participants with creatinine levels above institutional normal
    • Cardiac ejection fraction > 45% by echocardiogram
  • For phase 1: Participants must have received at least 1 prior line of systemic therapy for KS with either plateau in response, progressive disease, or inadequate response to treatment. Previous local therapy or radiation is not considered systemic therapy.
  • For phase 2: Group 2a: Participants must have received at least 1 prior line of systemic therapy for KS with either plateau in response, relapsed disease, progressive disease, or inadequate response to treatment
  • For phase 2: Group 2b: Participants have not received prior systemic therapy for KS. Previous local therapy or radiation is not considered systemic therapy.
  • Age >18 years
  • ECOG performance status <= 2 (Karnofsky >= 60%.
  • Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy are eligible for this trial.
  • Willingness to adhere to ART
  • For all arms of the study, participants must have received ART for 8 weeks prior to enrollment, with no evidence of KS improvement over the most recent 4 weeks
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • No uncontrolled severe concurrent bacterial, viral, or fungal infections.
  • Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
  • The effects of abemaciclib on the developing human fetus are unknown. For this reason and because CDK inhibitors are known to be teratogenic, persons of child-bearing potential and their sexual partners must agree to use adequate pregnancy contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study treatment. Should a person become pregnant or suspect they are pregnant while they or their partner is receiving study drug in this study, the pregnant person should inform their treating physician immediately. Participants with sexual partners of childbearing potential treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study treatment, and 4 months after completion of abemaciclib administration.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • 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.
  • 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.
  • Participants with 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.
  • Participants with psychiatric illness/social situations that would limit adherence with study requirements.
  • Pregnant persons are excluded from this study because abemaciclib is CDK inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the nursing person with abemaciclib, breastfeeding should be discontinued if the nursing person is treated with abemaciclib.
  • Participants with a 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04941274


Contacts
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Contact: Anaida Widell (240) 760-6074 anaida.widell@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ramya M Ramaswami, M.D. National Cancer Institute (NCI)
Additional Information:
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04941274    
Other Study ID Numbers: 210026
21-C-0026
First Posted: June 28, 2021    Key Record Dates
Last Update Posted: November 5, 2021
Last Verified: November 1, 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Angiogenesis
AIDS
cyclin-dependent kinase
KSHV
Cell Cycle
Additional relevant MeSH terms:
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Sarcoma, Kaposi
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Infections
Neoplasms, Vascular Tissue