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

SIR-DA-1202

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)

2017-06-14

2019-10-02

2020-10-27

Terminated

Early phase I

4

Inclusion Criteria: * Diagnosis: All patients must have one of the following vascular anomalies as determined by clinical, radiologic and histologic criteria (when possible). Biopsy strongly recommended (but not required) with suggested immunostains: CD34, PROX-1 or D240, Glut-1 and MIB-1. 1. Kaposiform Hemangioendotheliomas 2. Tufted angioma High Risk Stratification: In addition to the above diagnosis, all of the following criteria need to be met: a. Kasabach Merritt Syndrome defined at a platelet counts less than 50,000 K/µl and/or fibrinogen level \< 100 mg/dl at the time of diagnosis. * Age: Patients must be 0 - 31 years of age at the time of study entry. Enrollment includes patients of both genders and all ethnic groups. * Organ function requirements: 1. Adequate liver function defined as: 1. Total bilirubin ≤ 1.5 x ULN for age, and 2. SGPT (ALT) ≤ 5 x ULN for age, and 3. Serum albumin \>/= 2 g/dL. 4. Fasting LDL cholesterol of \<160 mg/dL 5. Fasting triglyceride \<400 mg/dl 2. Adequate Bone Marrow Function defined as: 1. Peripheral absolute neutrophil count (ANC) \>/= 1000/uL 2. Hemoglobin \>/= 8.0 g/dL (may receive RBC transfusions) 3. No Platelet requirement 3. Adequate Renal Function Defined as: 1. A serum creatinine based on age as follows: Age (Years) Maximum Serum Creatinine (mg/dL) * 5 0.8 6 to ≤10 1.0 11 to ≤15 1.2 \>15 1.5 2. Urine protein to creatinine ratio (UPC) \< 0.3 g/l * Performance Status: Karnofsky \>/= 50 (≥16 years of age) and Lansky \>/= 50 for patients \<16 years of age. * Prior therapy 1. Patients who have undergone surgical resection or interventional radiology procedures for disease control are eligible if they meet all inclusion criteria after surgery/procedure 2. Surgery: At least 2 weeks since undergoing any major surgery 3. Radiation: \> 6 months from involved field radiation 4. Prior vincristine therapy is permitted. Patients may also have received up to 2 doses of vincristine prior to randomization. Exclusion Criteria: * Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration). * Patients who require medications that are strong inhibitors/inducers CYP3A4 enzyme activity, including anticonvulsants, (Appendix II) to control concurrent medical conditions are not eligible. Patients who discontinue use of prohibited medications with a one week washout prior to start of study treatment are eligible. * Known history of HIV seropositivity or known immunodeficiency. Testing is not required unless a condition is suspected. * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of sirolimus (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection). A gastric tube or nasogastric tube is allowed. * Females who are pregnant or breast feeding. * Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during the period they are receiving the study drug and for 3 months thereafter. Abstinence is an acceptable method of birth control. Females of childbearing potential will be given a pregnancy test within 7 days prior to administration of study treatment and must have a negative urine or serum pregnancy test. * Patients who have received prior treatment with an mTOR inhibitor. * Patients unwilling or unable to comply with the protocol or who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study. * Patients who currently have an uncontrolled infection, defined as receiving intravenous antibiotics.

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2023-09-21