Ignite Creation Date:
2024-05-06 @ 4:18 PM
Last Modification Date:
2024-10-26 @ 2:07 PM
Study NCT ID:
NCT04941274
Status:
RECRUITING
Last Update Posted:
2024-07-05
First Post:
2021-06-25
Brief Title:
Abemaciclib in Patients With HIV-associated and HIV-negative Kaposi Sarcoma
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase III Study of Abemaciclib in Patients With HIV-associated and HIV-negative Kaposi Sarcoma
Status:
RECRUITING
Status Verified Date:
2024-09-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 andor 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
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 andor 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
Detailed 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 01 microM
Published Phase III 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 III 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 33 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
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 01 microM
Published Phase III 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 III 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 33 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 21-C-0026 | None | None | None |