Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Sarcoma

Histiocytoma, Malignant Fibrous

Hemangioendothelioma

Sarcoma, Synovial

Solitary Fibrous Tumors

Hemangiopericytoma

Neoplasms, Fibrous Tissue

Histiocytoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Hemangioma

Neoplasms, Vascular Tissue

Soft Tissue Sarcoma

Undifferentiated Pleomorphic Sarcoma

Synovial Sarcoma

Epithelioid Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Trabectedin

Antineoplastic Agents, Alkylating

Alkylating Agents

This study is a single arm study with biomarker analysis

- Trabectedin will be prescribed as per market authorization and will be administered by intraveinous infusion (1,5 mg/m²) every 3 weeks. A treatment cycle is defined as a 3-weeks period

Antoine ITALIANO, MD, PhD

Simone MATHOULIN-PELISSIER, MD, PhD

Antoine ITALIANO

This is a biology driven, monocentric study, designed to identify biomarkers of activity of trabectedin in patients with advanced non-L soft-tissue sarcoma. The aim of this study is to implement high-throughput profiling technologies to identify predictive biomarkers of trabectedin efficacy through sequential tumor biopsies and blood sample collection in sarcoma patients.

The identification of predictive biomarkers of the clinical benefit of trabectedin is a crucial issue to identify potential responders particularly for non-L sarcomas. Considering that the molecular profile of STS can change over time, an analysis of archival tumor material may not be a reliable method to identify predictive biomarkers of response, and thus high-throughput technologies may be promising to identify STS markers for prediction of response to trabectedin. For study purpose, blood and tumor samples will be obtained for genetic and immunological profiling at baseline, during treatment by trabectedin and at disease progression.

Prospective Identification of Predictive Biomarkers of Trabectedin Efficacy in Non-L Soft-tissue Sarcoma Patients

Efficacy of trabectedin is defined as objective response \[OR\] or stable disease \[SD\] \> 6 months. Absence of efficacy is defined as progressive disease \[PD\] within 2 months.

Toxicity graded using the Common Terminology Criteria for Adverse Events version 5.

Institut Bergonié

Diseases and Abnormalities at or Before Birth

Heart and Blood Diseases

Congenital Abnormalities

Hemangiosarcoma

Arteriovenous Malformations

Vascular Malformations

Cardiovascular Abnormalities

Vascular Diseases

Ethiodized Oil

Lipiodol® Ultra Fluid and surgical glue mixture may vary from 20 to 80% and should be administered via selective arterial catheterization only.

Lipiodol® Ultra Fluid with surgical glues

Corinne Dubourdieu

Camille Pitrou

Pierre DESCHE, MD

This study is multicenter (up to 10 sites in India) phase IV Post-Marketing Study. The study is designed to investigate the safety of Lipiodol® Ultra Fluid in association with surgical glues used according to each site medical practice of vascular embolization. Subjects will be enrolled with the main condition that a procedure of vascular embolization using Lipiodol® Ultra Fluid in association with surgical glues is part of their therapeutic/palliative strategy for their disease. The vascular embolization using Lipiodol® Ultra Fluid in association with surgical glue will be administered as study procedure. According to the patient need and health status a second vascular embolization using Lipiodol® Ultra Fluid in association with surgical glue may be considered by the investigator within the next 30 days after the first one. In this case, this procedure will be considered as a second study procedure. The per-procedure safety evaluation will be enabled by appropriate records of safety events during the time frame of the procedure of vascular embolization using Lipiodol® Ultra Fluid in association with surgical glues. Safety evaluation will be completed with safety records within 30 +/-3 days after the embolization procedure. Efficacy evaluation will rely on the level of lesion(s) obliteration after embolization compared to the pre-procedural target level of obliteration. Exploratory descriptive statistical methods will be used to evaluate safety and efficacy, using both the total population and subsets of subjects with similar clinical conditions.

Evaluation of Lipiodol® Ultra Fluid in Association With Surgical Glues During Vascular Embolization.

Safety and Efficacy of Lipiodol® Ultra Fluid in Association With Surgical Glues During Vascular Embolization. A Phase IV Study.

Guerbet

Symptoms and General Pathology

Blood and Lymph Conditions

Infections

Syndrome

Kasabach-Merritt Syndrome

Vascular Neoplasms

Sarcoma, Kaposi

Communicable Diseases

Herpesviridae Infections

Virus Diseases

DNA Virus Infections

Thrombocytopenia

Blood Platelet Disorders

Hematologic Diseases

Cytopenia

Kaposiform Hemangioendothelioma

Tufted Angioma

Hemangioma Thrombocytopenia Syndrome

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prospective Identification of Predictive Biomarkers of Trabectedin Efficacy in Non-L Soft-tissue Sarcoma Patients	NCT04008238	Soft Tissue Sar... Undifferentiate... Epithelioid Sar... Solitary Fibrou... Hemangioendothe... Desmoplastic Ro... Synovial Sarcom...	Trabectedin	18 Years -	Institut Bergonié
Evaluation of Lipiodol® Ultra Fluid in Association With Surgical Glues During Vascular Embolization.	NCT02625389	Congenital Hema... Hemangioendothe... Angiosarcoma Arteriovenous M...	Lipiodol® Ultra...	18 Years -	Guerbet
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
Evaluation of Lipiodol® Ultra Fluid in Association With Surgical Glues During Vascular Embolization.	NCT02625389	Congenital Hema... Hemangioendothe... Angiosarcoma Arteriovenous M...	Lipiodol® Ultra...	18 Years -	Guerbet
Evaluation of Lipiodol® Ultra Fluid in Association With Surgical Glues During Vascular Embolization.	NCT02625389	Congenital Hema... Hemangioendothe... Angiosarcoma Arteriovenous M...	Lipiodol® Ultra...	18 Years -	Guerbet

Spots Global Cancer Trial Database for hemangioendothelioma