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Sarcoma, Kaposi

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Neoplasms, Vascular Tissue

Soft Tissue Sarcoma

Kaposi Sarcoma

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.

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

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

Abemaciclib

Anaida Widell

Ramya M Ramaswami, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

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.

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.

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

A Phase I/II Study of Abemaciclib in Patients With HIV-associated and HIV-negative Kaposi Sarcoma

.All IPD recorded in the medical record will be shared with intramural investigators upon request.

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

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

Staging and response to abemaciclib for KS by the evaluation of number, size, nodularity, and color of lesions.

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

Duration of time from the start of the treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first

National Cancer Institute (NCI)

Skin and Connective Tissue Diseases

Herpes Simplex

Cases with Kaposi's Sarcoma from Southern Italy.

Sam M Mbulaiteye, M.D.

This study will try to identify risk factors for Kaposi s sarcoma, a rare skin cancer, and to understand the role of the KSHV virus in development of the disease.

All native-born Italians 21 years of age or older residing in Sicily from July 1, 2002 through June 30, 2005 who have Kaposi s sarcoma not related to HIV infection may be eligible for this study. Healthy control subjects will also be enrolled.

All participants will be interviewed about their childhood, jobs, habits, medical conditions, and treatments. They also will provide a blood sample and a saliva sample, obtained by swishing a mouthwash for 45 seconds and spitting it into a container.

Blood will be tested for two viruses KSHV and HIV that are related to Kapsosi s sarcoma. The KSHV virus is newly discovered and not well understood. In general, a positive KSHV test probably means an infection with the virus has occurred in the past, but not necessarily that disease has developed. HIV is the virus that causes AIDS. People with AIDS have a high risk of Kapsosi s sarcoma. Although HIV and AIDS are very rare among older adults in Sicily, the presence of HIV must be ruled out in order to understand how KSHV is related to Kapsosi s sarcoma.

The blood may also be used to measure immunity (the body s defense against infection and cancer) and for genetic studies to help discover why Kapsosi s sarcoma occurs.

Persons infected with the Kaposi s sarcoma-associated herpesvirus (KSHV) are at risk for developing Kaposi s sarcoma (KS), but the risk factors for KSHV infection and for KS following infection are not well defined. Classical KS (cKS) occurs without apparent immune deficiency (such as AIDS or an allograft). The proposed study will test specific hypotheses and generate new hypotheses on the risk of cKS among persons who have antibodies against KSHV, on the risk of KSHV seropositivity, and on the risk of active KSHV infection, defined as KSHV viremia or viral shedding in saliva. To do so, 120 incident cases of cKS from throughout Sicily and approximately 1800 persons (15% KSHV seropositive) of similar age, sex, and community size will be asked to participate by providing questionnaire data and blood and saliva specimens. Residual formalin-fixed, paraffin embedded tissue from KS skin biopsies will be available for verification of diagnosis and molecular analyses. Primary hypotheses are focused on host genetic susceptibility, endogenous clinical conditions (such as asthma and allergy), and exogenous exposures (cigarette smoking and contact with certain plants, water and soil) that are postulated to affect KSHV activation, dissemination, and disease induction. The study will have sufficient statistical power to detect factors that increase the risk of KSHV seropositivity by 1.5- to 2-fold, the risk of cKS by 2- to 3-fold, and the risk of KSHV viremia or shedding by 3- to 4-fold.

Risk Factors for Non-HIV-Related Kaposi s Sarcoma

Cofactors for Classical Kaposi's Sarcoma and for Kaposi's Sarcoma-Associated Herpesvirus Infection: A Case-Control Study in Sicily

HIV Seropositivity

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Antibodies

Immunoglobulins

Mitogens

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

15 mg/kg bevacizumab intravenously on days 1 and 8 then every 3 weeks.

15 mg/kg day intravenously on day 1, day 8, then every 3 weeks.

Robert Yarchoan, M.D.

This study will examine the safety and effectiveness of the experimental drug bevacizumab for treating both non-acquired immune deficiency syndrome (AIDS) and AIDS-associated Kaposi's sarcoma (KS). KS tumors depend on the formation of new blood vessels for their growth. Bevacizumab is an antibody to a protein called vascular endothelial growth factor (VEGF) that is produced by the body and is involved in blood vessel growth. Bevacizumab may block the action of VEGF, and thus help shrink KS lesions.

Patients 18 years of age and older with Kaposi's sarcoma that is restricted to the skin and is not life threatening may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), chest x-ray, and, if needed, imaging studies to evaluate internal tumors.

Participants will receive bevacizumab intravenously (by vein) once a week for 2 weeks and then every 3 weeks at the National Institutes of Health (NIH) Clinical Center. The first infusion takes about 90 minutes, the second takes about 60 minutes, and subsequent infusions take about 30 minutes. Infusions may take longer, however, if the drug is better tolerated at a slower infusion rate. Patients will be evaluated with the following tests and procedures:

* Physical examination, assessment of drug side effects, measurement of KS lesions, and photographs of lesions once a week for the first 6 weeks of therapy, and then every 3 weeks.
* cluster of differentiation 4 (CD4) cell counts and human immunodeficiency virus (HIV) viral load in HIV-positive patients every 12 weeks.
* Biopsies of lesions: upon entering the study, at week 12, and at the time of a response of the tumor to therapy or at the end of treatment, if treatment ends at week 18 or later.
* Additional biopsies, if requested. (Additional biopsies are not required.)
* Other procedures, such as computed tomography (CT) or magnetic resonance imaging (MRI) scans, if medically indicated.

Patients may continue bevacizumab therapy indefinitely if they are benefiting from it, as long as they have no substantial toxicity or other conditions that would cause them to stop receiving it and the protocol remains open.

BACKGROUND:

This is a phase II study to determine the activity of bevacizumab, a putative antiangiogenic agent, in Kaposi's sarcoma (KS). Bevacizumab is a humanized recombinant antibody to vascular endothelial cell growth factor (VEGF), an important cytokine in the pathogenesis of KS.

OBJECTIVES:

To assess the antitumor effect of bevacizumab 15 mg/kg administered intravenously once every three weeks in patients with human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS). Other objectives include assessment of the antitumor effect of bevacizumab 15 mg/kg administered intravenously once every three weeks in patients with classical KS; assessment of the toxicity profile of bevacizumab in HIV-infected and HIV-negative patients with KS; exploration in a preliminary fashion effect of bevacizumab on KS progression free survival; and study of a number of biochemical parameters, including stromal cell-derived factor-1 (SDF-1) expression in KS lesions; human herpes virus-8 (HHV-8) viral load in peripheral blood mononuclear cells; serum vascular endothelial growth factor (VEGF) levels over the course of treatment; and changes in viral interleukin 6 (IL-6) levels over the course of treatment.

ELIGIBILITY:

Key eligibility parameters include HIV-associated or classical Kaposi's sarcoma, age greater than or equal to 18 years, and life expectancy greater than 6 months. Patients with HIV infection must have either KS progression on a regimen of highly active antiretroviral therapy (HAART) for at least one month, or no KS regression while on an optimized regimen of HAART for 4 months or longer.

DESIGN:

Patients will be sequentially enrolled, administered a loading dose of 15 mg/kg bevacizumab intravenously on day 1, and then administered 15 mg/kg bevacizumab intravenously every 3 weeks beginning one week after the loading dose. The drug will be temporarily discontinued for toxicity, intercurrent major surgical procedures, or other factors that would pose a safety concern. Patients will undergo a biopsy of a KS lesion at entry, on cycle 4, day 21, and at the time of a formal response or when the patient stops treatment. Patients will undergo a number of other tests as well, including blood tests and non-invasive imaging studies of KS lesions.

Bevacizumab to Treat Kaposi's Sarcoma in HIV-Positive and HIV-Negative Patients

Phase II Study of Intravenous Recombinant Humanized Anti-Vascular Endothelial Cell Growth Factor Antibody (Bevacizumab) in Classical (HIV-Negative) and in AIDS-Associated Kaposi's Sarcoma

Percentage of participants with a complete response (CR) + partial response (PR)per the Modified AIDS Clinical Trial Group Criteria (ACTG) for HIV-KS. PR is a 50% decrease in the number and/or size of previously existing lesions for 4 weeks; or complete flattening of at least 50% of all previously raised lesions lasting for at least 4 weeks; or a 50% decrease in the sum of the products of the largest perpendicular diameters of the marker lesions lasting for at least 4 weeks; CR is the absence of any detectable residual disease, including tumor associated edema, persisting for at least 4 weeks.

Here are the number of participants with adverse events. For the detailed list of adverse events, see the adverse event module.

Principal Investigator

15 mg/kg bevacizumab intravenously on days 1 and 8 then every 3 weeks

Cohort 1 & 2: Pts With HIV-associated and Classic KS

Cohort 1: Cohort 1: Pts With HIV-associated Kaposi's Sarcoma

Cohort 2: Pts With Classic Kaposi's Sarcoma (HIV-uninfected)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Cohort 2 is not reported here because response rate in HIV negative patients was a secondary outcome.

Response Rate

All adverse events regardless of attribution, over 202 cycles in 19 patients. Per protocol analysis of adverse events.

Cohort 1 and 2 are reported together.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Abemaciclib in Patients With HIV-associated and HIV-negative Kaposi Sarcoma	NCT04941274	Kaposi Sarcoma	Abemaciclib	18 Years -	National Institutes of Health Clinical Center (CC)
Risk Factors for Non-HIV-Related Kaposi s Sarcoma	NCT00339326	Kaposi's Sarcom...		18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Abemaciclib in Patients With HIV-associated and HIV-negative Kaposi Sarcoma	NCT04941274	Kaposi Sarcoma	Abemaciclib	18 Years -	National Institutes of Health Clinical Center (CC)
Bevacizumab to Treat Kaposi's Sarcoma in HIV-Positive and HIV-Negative Patients	NCT00055237	Kaposi's Sarcom... HIV Infections HIV Seronegativ...	Bevacizumab	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for kshv

Every month we try and update this database with for kshv cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for kshv

Every month we try and update this database with for kshv cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for kshv cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.