This study is currently recruiting participants.
Number
21-C-0026
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Fetuses;Pregnant Women;Children
Keywords
Angiogenesis; AIDS; cyclin-dependent kinase; KSHV; Cell Cycle
Recruitment Keyword(s)
None
Condition(s)
Kaposi Sarcoma
Investigational Drug(s)
Investigational Device(s)
Intervention(s)
Drug: Abemaciclib
Supporting Site
National Cancer Institute
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.
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INCLUSION CRITERIA: - 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 --Cardiac ejection fraction > 45% by echocardiogram - Prior Treatment as follows: --For Phase I: 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 II: Group 2a: Individuals 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 II: Group 2b: Individuals have not received prior systemic therapy for KS. Previous local therapy or radiation is not considered systemic therapy. - For Phase II: Group 3: Evidence of Stage T1 KS with either a) edema or ulcerated KS and/or b) extensive oral KS and/or c) visceral KS involvement - Age >18 years - Eastern Cooperative Oncology Group (ECOG) performance status (PS) <= 2 (Karnofsky >= 60%. - Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy are eligible for this trial. - Willingness to adhere to ART - All 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. Participants with HCV infection who are currently on treatment 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. -Contraception requirements as follows: --Participants of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (e.g., intrauterine device [IUD], hormonal, surgical sterilization, abstinence) prior to study entry, for the duration of study participation, and for up to 4 months after completion of abemaciclib administration --Participants able to father a child must with partners of childbearing potential agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment for up to 4 months after completion of abemaciclib administration. Individuals with partners of childbearing potential should ask their partners to be on an effective birth control (hormonal, IUD, surgical sterilization). -Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the nursing person with abemaciclib, nursing should be discontinued if the nursing person is treated with abemaciclib. - 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 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
- 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
--Cardiac ejection fraction > 45% by echocardiogram
- Prior Treatment as follows:
--For Phase I: 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 II: Group 2a: Individuals 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 II: Group 2b: Individuals have not received prior systemic therapy for KS. Previous local therapy or radiation is not considered systemic therapy.
- For Phase II: Group 3: Evidence of Stage T1 KS with either a) edema or ulcerated KS and/or b) extensive oral KS and/or c) visceral KS involvement
- Age >18 years
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) <= 2 (Karnofsky >= 60%.
- Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy are eligible for this trial.
- Willingness to adhere to ART
- All 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. Participants with HCV infection who are currently on treatment 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.
-Contraception requirements as follows:
--Participants of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (e.g., intrauterine device [IUD], hormonal, surgical sterilization, abstinence) prior to study entry, for the duration of study participation, and for up to 4 months after completion of abemaciclib administration
--Participants able to father a child must with partners of childbearing potential agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment for up to 4 months after completion of abemaciclib
administration. Individuals with partners of childbearing potential should ask their partners to be on an effective birth control (hormonal, IUD, surgical sterilization).
-Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the nursing person with abemaciclib, nursing should be discontinued if the nursing person is treated with abemaciclib.
- 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 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
Principal Investigator
Referral Contact
For more information: