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

NCT02110069 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: SIR-DA-12021R01FD004363-01A12013-2339
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 7

Brief Summary

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)

Conditions

Kaposiform Hemangioendothelioma (KHE); Kasabach-Merritt Syndrome; Tufted Angioma

Keywords

KHE; Vascular anomaly; Kasabach-Merritt Syndrome; Tufted angioma; hemangioendothelioma

Outcome Measures

Primary Outcomes (2)

• Change in Hematologic Parameters

  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.

  2 months

• Number of Serious and Non-Serious Adverse Events

  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.

  2 months; 12 months

Secondary Outcomes (4)

• Evaluation of Disease Response - Maintenance

  6 months; 12 months

• Number of Serious and Non Serious Adverse Events - Maintenance

  6 months; 12 months

• Change in the Serum Levels of KHE Biomarkers

  Baseline, 2 months, 6 months, and 12 months

• Identify Genetic Variants in Drug Metabolism Enzymes.

  Baseline

Study Arms (2)

Vincristine

ACTIVE COMPARATOR

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.

Drug: Vincristine

Sirolimus

EXPERIMENTAL

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.

Drug: Sirolimus

Interventions

Vincristine DRUG

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)

Also known as: Oncovin, Vincasar® PFS, Vincrex

Vincristine

Sirolimus DRUG

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

Also known as: Rapamune

Sirolimus

Eligibility Criteria

• Age: Up to 31 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• Kaposiform Hemangioendotheliomas
• 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:
• Adequate liver function defined as:
• Total bilirubin ≤ 1.5 x ULN for age, and
• SGPT (ALT) ≤ 5 x ULN for age, and
• Serum albumin \>/= 2 g/dL.
• Fasting LDL cholesterol of \<160 mg/dL
• Fasting triglyceride \<400 mg/dl
• Adequate Bone Marrow Function defined as:
• Peripheral absolute neutrophil count (ANC) \>/= 1000/uL

You may not qualify if:

• 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.

Sponsors & Collaborators

• Boston Children's Hospital: lead
• Pfizer: collaborator

Study Sites (7)

Lucille Packard Children's Hospital Stanford

Palo Alto, California, 94304, United States

Location

Emory Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Texas Children's Hospital

Houston, Texas, 77094, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Links

• Cincinnati Children's Hospital Medical Center Hemangioma and Vascular Malformation Center
• National Organization of Vascular Anomalies

MeSH Terms

Conditions

Kaposiform Hemangioendothelioma; Kasabach-Merritt Syndrome; Tufted angioma; Vascular Malformations; Hemangioendothelioma

Interventions

Vincristine; Sirolimus

Condition Hierarchy (Ancestors)

Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia; Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Denise M. Adans
• Organization: Boston Children's Hospital

adamsdm@chop.edu

617-919-6407

Study Officials

• Denise Adams, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: April 8, 2014
• First Posted: April 10, 2014
• Study Start: June 14, 2017
• Primary Completion: October 2, 2019
• Study Completion: October 27, 2020
• Last Updated: September 21, 2023
• Results First Posted: May 24, 2021

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)