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

  • STATUS
    Recruiting
  • End date
    Jun 1, 2028
  • participants needed
    43
  • sponsor
    National Cancer Institute (NCI)
Updated on 9 October 2021
cancer
immunodeficiency
systemic therapy
measurable disease
breast cancer
protease
atazanavir
cytotoxic chemotherapy
progressive disease
neutrophil count
AIDS

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.

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.

Details
Condition Kaposi's Sarcoma, Sarcoma, kaposi sarcoma
Treatment Abemaciclib
Clinical Study IdentifierNCT04941274
SponsorNational Cancer Institute (NCI)
Last Modified on9 October 2021

Eligibility

Yes No Not Sure

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

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.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note