Symptoms and General Pathology

All Conditions

Diseases and Abnormalities at or Before Birth

Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Infections

Rare Diseases

Syndrome

Congenital Abnormalities

Hemangioendothelioma

Vascular Malformations

Hemangioma

Kasabach-Merritt Syndrome

Neoplasms, Vascular Tissue

Vascular Neoplasms

Sarcoma

Sarcoma, Kaposi

Neoplasms by Histologic Type

Communicable Diseases

Herpesviridae Infections

Virus Diseases

DNA Virus Infections

Neoplasms, Connective and Soft Tissue

Thrombocytopenia

Blood Platelet Disorders

Hematologic Diseases

Cytopenia

Kaposiform Hemangioendothelioma

Tufted Angioma

Hemangioma Thrombocytopenia Syndrome

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Central Nervous System Depressants

Other Dietary Supplements

Vincristine

Sirolimus

Benzocaine

Temsirolimus

MTOR Inhibitors

Tubulin Modulators

Antimitotic Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Clotrimazole

Miconazole

Antifungal Agents

Immunosuppressive Agents

Immunologic Factors

Tannic Acid

Induction phase: participants assigned to vincristine will receive vincristine weekly at a dose of 0.05mg/kg/dose IV (for participants less than 10kg) or a dose of 1.5 mg/m2/dose (for participants greater than 10kg) for 2 months.

Maintenance: if participants continue to receive vincristine weekly for 2 months, every 2 weeks for 5 months and every 3 weeks for 5 months.

Sirolimus will be administered at a dose of 0.8mg/m2/dose twice a day on a continuous dosing schedule throughout the trial for participants randomized to Sirolimus or for participants who fail vincristine may cross-over to the sirolimus arm.

Sirolimus trough levels will be maintained between 10-15 ng/ml.

Vincristine dose dependent upon weight. Weekly for 2 months (Induction); Weekly 2 months; every 2 weeks for next 5 months; every 3 weeks for 5 months (Maintenance)

Continuous dosing to maintain trough level of 10-15ng/ml.

Denise Adams, MD

In this research study we want to learn more about which treatment works better for patients diagnosed with a vascular tumor called Kaposiform Hemangioendothelioma (KHE) or other high risk vascular tumors such as Tufted Angioma (TA). In these tumors, the blood cells that help your blood clot called platelets become trapped in the tumor causing swelling, pain, and bruising. Vascular tumors can be life threatening. There are few medical treatments that will work to shrink the vascular tumor. Some doctors will use steroids and vincristine to try and shrink vascular tumors.

In this research study, the study doctor will compare two different drugs to see which one will work better to help shrink your vascular tumor. One of the drugs is vincristine. Vincristine is approved by the Food and Drug Administration (FDA) to treat people with cancer. Vincristine is used to stop the abnormal cells from growing such as cells that make up blood vessels.

The other drug to be used in this study is sirolimus. Sirolimus is currently approved by the Food and Drug Administration (FDA) to prevent transplanted organ rejection. Sirolimus is not approved by the FDA for treatment of vascular abnormalities and is considered experimental. Sirolimus belongs to a class of drugs call 'mTOR inhibitors'. mTOR (mammilian target of rapamycin) helps cells to grow and may also help blood vessels to grow in a more normal fashion. Sirolimus is currently being tested in patients with vascular tumors and cancer. In vascular tumors, we hope sirolimus will stop the blood vessel growth.

Funding Source: FDA - OOPD (Office of Orphan Products Development)

Kaposiform hemangioendotheliomas (KHE) are extremely rare life threatening tumors which can be associated with Kasabach-Merritt Phenomenon consisting of profound thrombocytopenia and hypofibrinogenemia causing a significant risk of bleeding and an associated mortality rate as high as 20% to 30%. Despite the severity of potential complications, we lack uniform guidelines for the treatment and response to treatment of children and young adults with these tumors. KHE patients have been treated with a multitude of aggressive drug regimens without prospective evaluation of response or safety. Presently, vincristine is considered the standard of practice. We have treated a subset of these patients on study SIR-DA-0901 (FDA Grant# 5RO1FD003712-01). This study is a phase II trial assessing the efficacy and safety of sirolimus for the treatment of complicated vascular anomalies. Although the numbers are small, the response has been extremely promising with excellent tolerability. There is pre-clinical and clinical data supporting the essential regulatory function of the PI3 kinase/AKT/mTOR pathway in vascular growth and organization which suggests a therapeutic target for patients with complicated vascular anomalies. The overall goal of this trial is to objectively assess the efficacy of sirolimus compared to vincristine for the treatment of patients with high risk KHE.

Hypothesis: Sirolimus treatment for children and young adults with Kaposiform hemangioendotheliomas will be more effective than vincristine, assessed by time to response in an induction period and provide equivalent safety parameters.

Study Rationale We propose a multi-center, phase II trial with participation from 8 sites. The study will consist of two phases. The first of these is an initial induction phase in which vincristine and steroids will be compared to sirolimus and steroids. Response in the induction phase will be assessed as time to hematologic response. At the end of induction phase, cross over can occur if there is failure to respond. Part 2 is a maintenance phase which will be 1 year in length. Continued safety and efficacy data will be collected during maintenance and there will be cross over at any time for patients who lose their response following induction. Failure will be defined as worsening of hematological parameters on two separate laboratory evaluations at any time during maintenance or if they meet the definition of progressive disease following response assessments. Formal response in maintenance will be evaluated by imaging studies, functional assessment, and quality of life as per study SIR-DA-0901. Present therapies are very limited and new therapies are desperately needed for this devastating disease. Based on our preliminary data, there is a very good rationale for sirolimus therapy in KHE patients and so a phase II trial is urgently needed to determine if this therapy is to become the new standard of care for KHE patients.

Our secondary aims will be addressing biomarker analysis. There are limited studies describing the biology of these tumors. Per study SIR-DA-0901 there is some preliminary data indicating the importance of VEGF-C and other upregulated markers in the mTor pathway. This needs to be further investigated especially in KHE patients. Furthermore there are no clear objective measurements to determine response data.

A Study to Compare Vincristine to Sirolimus for Treatment of High Risk Vascular Tumors

A Randomized Phase 2 Study of Vincristine Versus Sirolimus to Treat High Risk Kaposiform Hemangioendothelioma (KHE).

Hematologic parameters are defined as a platelet count greater than 100,000/uL (or a 2 times increase in platelet count compared to baseline) and a fibrinogen level greater than 150mg/dl.

Serious and non-serious adverse events will be recorded for all participants and graded using CTCAE v4.0 (Common Toxicity Criteria for Adverse Effects). Adverse event rates will be calculated for both sirolimus and vincristine.

Disease evaluation will be measured using a combination of quality of life assessments, clinical parameters, and radiologic images.

Serious adverse events and adverse events will be graded according to CTCAE v4.0. Adverse event rates will be calculated for both sirolimus and vincristine.

The following KHE biomarkers will be evaluated vascular endothelial growth factor A, C, and D (VEGF-A, C, D_, IL-8 (interleukin), Pleiotrophin, IGF-1 (insulin-like growth factor), endothelin-1, thrombospondin and angiopoietin 1 and 2.

Single nucleotide polymorphism array analysis to obtain genetic information on variants in drug metabolism enzymes that affect sirolimus and vincristine metabolism.

Pfizer

Boston Children's Hospital

Associate Professor

Induction phase: participants assigned to vincristine will receive vincristine weekly at a dose of 0.05mg/kg/dose IV (for participants less than 10kg) or a dose of 1.5 mg/m2/dose (for participants greater than 10kg) for 2 months.

Maintenance: if participants continue to receive vincristine weekly for 2 months, every 2 weeks for 5 months and every 3 weeks for 5 months.

Vincristine: Vincristine dose dependent upon weight. Weekly for 2 months (Induction); Weekly 2 months; every 2 weeks for next 5 months; every 3 weeks for 5 months (Maintenance)

Sirolimus will be administered at a dose of 0.8mg/m2/dose twice a day on a continuous dosing schedule throughout the trial for participants randomized to Sirolimus or for participants who fail vincristine may cross-over to the sirolimus arm.

Sirolimus trough levels will be maintained between 10-15 ng/ml.

Sirolimus: Continuous dosing to maintain trough level of 10-15ng/ml.

Total

Age, Categorical

There was no analysis as study was closed early

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Number of participants with platelet count & fibrinogen levels

no analysis was performed as study was closed early

Dr. Denise M. Adans

no analysis was performed due to study being closed for low enrollment

Change in Hematologic Parameters

study was closed early due to slow enrollment

Number of Serious and Non-Serious Adverse Events

Evaluation of Disease Response - Maintenance

no data analyzed as study was closed early

Number of Serious and Non Serious Adverse Events - Maintenance

no analysis performed as study was closed early

Change in the Serum Levels of KHE Biomarkers

study closed early due to slow enrollment

Identify Genetic Variants in Drug Metabolism Enzymes.

Overall Study

Musculoskeletal Diseases

Nervous System Diseases

Nevus, Pigmented

Klippel-Trenaunay-Weber Syndrome

Nevus

Osteolysis

Osteolysis, Essential

Sturge-Weber Syndrome

Cardiovascular Abnormalities

Angiomatosis

Vascular Diseases

Bone Diseases

Bone Diseases, Developmental

Bone Resorption

Klippel-Trenaunay Syndrome

Parkes Weber Syndrome

Weber Syndrome

CLOVES Syndrome

Lymphangiomatosis

Kaposiform Lymphangiomatosis

Gorham's Disease

Endothelial Growth Factors

Mitogens

Timothy LeCras, PhD

Megan Metcalf

Adrienne Hammill, MD, PhD

The study will use blood (serum and plasma) and tissue obtained from participants undergoing prescribed surgical resection of vascular anomalies of interest proposed in this study. The study will also use blood (serum and plasma) and tissue collected and stored in a tissue bank maintained by the Department of Hematology/Oncology.

While vascular anomalies are rare diseases, they can be life-threatening and devastating to affected children and their families. Advances in diagnosis, monitoring and therapies will be significantly improved if non-invasive biomarkers that are sensitive and specific can be identified. Obtaining a tissue biopsy to help in diagnosis can actually worsen the disease and so identification of specific blood biomarkers is highly desirable. Studies will measure angiogenic factors in serum and plasma samples at baseline and on therapy. Tissue removed during surgical resection or blood removed prior to sclerotherapy will be used to obtain cells and tissue for the assessment of where biomarkers are coming from and to identify disease-causing pathways for new therapeutic targeting.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study to Compare Vincristine to Sirolimus for Treatment of High Risk Vascular Tumors	NCT02110069	Kaposiform Hema... Kasabach-Merrit... Tufted Angioma	Vincristine Sirolimus	- 31 Years	Boston Children's Hospital
Identification of Biomarkers for Patients With Vascular Anomalies	NCT03001180	Vascular Anomal... Generalized Lym... Kaposiform Hema... Kaposiform Lymp... Gorham-Stout Di... Klippel Trenaun... Congenital Lipo...		1 Day -	Children's Hospital Medical Center, Cincinnati
Identification of Biomarkers for Patients With Vascular Anomalies	NCT03001180	Vascular Anomal... Generalized Lym... Kaposiform Hema... Kaposiform Lymp... Gorham-Stout Di... Klippel Trenaun... Congenital Lipo...		1 Day -	Children's Hospital Medical Center, Cincinnati

Spots Global Cancer Trial Database for khe

Every month we try and update this database with for khe 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 khe

Every month we try and update this database with for khe 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 khe 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.