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

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ClinicalTrials.gov Identifier: NCT02110069
Recruitment Status : Terminated (This study was challenged by the incidence of KHE with KMP as this continued to be extremely rare, and very sporadic. In July of 2019 grant renewal funding ended.)
First Posted : April 10, 2014
Results First Posted : May 24, 2021
Last Update Posted : May 24, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Denise Martin Adams, Boston Children's Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Kaposiform Hemangioendothelioma (KHE)
Kasabach-Merritt Syndrome
Tufted Angioma
Interventions Drug: Vincristine
Drug: Sirolimus
Enrollment 4
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vincristine Sirolimus
Hide Arm/Group Description

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.

Period Title: Overall Study
Started 2 2
Completed [1] 0 [2] 2 [3]
Not Completed 2 0
[1]
second subject came off study at maintenance course 6 as family moved out of the country
[2]
subject was switched to sirolimus at maintenance course 7 for failure on Vincristine
[3]
1 subject was takend off protocol treatment at 10 months of maintenance for disease response.
Arm/Group Title Vincristine Sirolimus Total
Hide Arm/Group Description

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 of all reporting groups
Overall Number of Baseline Participants 2 2 4
Hide Baseline Analysis Population Description
no analysis was performed as study was closed early
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 4 participants
<=18 years
2
 100.0%
2
 100.0%
4
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous   [1] 
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 0 participants 0 participants 0 participants
[1]
Measure Analysis Population Description: There was no analysis as study was closed early
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 4 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
2
 100.0%
2
 100.0%
4
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 4 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
2
 100.0%
2
 100.0%
4
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2 participants 2 participants 4 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  50.0%
1
  50.0%
2
  50.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  50.0%
0
   0.0%
1
  25.0%
White
0
   0.0%
1
  50.0%
1
  25.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 2 participants 2 participants 4 participants
2 2 4
1.Primary Outcome
Title Change in Hematologic Parameters
Hide Description 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.
Time Frame 2 months
Hide Outcome Measure Data
Hide Analysis Population Description
no analysis was performed due to study being closed for low enrollment
Arm/Group Title Vincristine Sirolimus
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Primary Outcome
Title Number of Serious and Non-Serious Adverse Events
Hide Description 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.
Time Frame 2 months; 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
study was closed early due to slow enrollment
Arm/Group Title Vincristine Sirolimus
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Evaluation of Disease Response - Maintenance
Hide Description Disease evaluation will be measured using a combination of quality of life assessments, clinical parameters, and radiologic images.
Time Frame 6 months; 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
no analysis was performed
Arm/Group Title Vincristine Sirolimus
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Number of Serious and Non Serious Adverse Events - Maintenance
Hide Description 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.
Time Frame 6 months; 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
no data analyzed as study was closed early
Arm/Group Title Vincristine Sirolimus
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Change in the Serum Levels of KHE Biomarkers
Hide Description 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.
Time Frame Baseline, 2 months, 6 months, and 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
no analysis performed as study was closed early
Arm/Group Title Vincristine Sirolimus
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Identify Genetic Variants in Drug Metabolism Enzymes.
Hide Description Single nucleotide polymorphism array analysis to obtain genetic information on variants in drug metabolism enzymes that affect sirolimus and vincristine metabolism.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
study closed early due to slow enrollment
Arm/Group Title Vincristine Sirolimus
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame 14 months for 2 subjects 12 months for 1 subject 6 months for 1 subject
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vincristine Sirolimus
Hide Arm/Group Description

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.

All-Cause Mortality
Vincristine Sirolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   0/2 (0.00%)      0/2 (0.00%)    
Hide Serious Adverse Events
Vincristine Sirolimus
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/2 (50.00%)      1/2 (50.00%)    
Infections and infestations     
Lung infection  1 [1]  1/2 (50.00%)  1 0/2 (0.00%)  0
Lung infection  1 [2]  1/2 (50.00%)  1 0/2 (0.00%)  0
Sepsis  1 [3]  0/2 (0.00%)  0 1/2 (50.00%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
Subject admitted to hospital and test positive for adenovirus
[2]
Subject tested positive for RSV
[3]
Central Line Associated BloodStream Infection
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Vincristine Sirolimus
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/2 (50.00%)      2/2 (100.00%)    
Blood and lymphatic system disorders     
anemia  1 [1]  0/2 (0.00%)  0 2/2 (100.00%)  2
Neutrophil count decreased  1 [1]  0/2 (0.00%)  0 2/2 (100.00%)  2
Infections and infestations     
Fever  1 [1]  1/2 (50.00%)  1 1/2 (50.00%)  1
1
Term from vocabulary, CTCAE (4.0)
Indicates events were collected by systematic assessment
[1]
Grade 2
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Denise M. Adans
Organization: Boston Children's Hospital
Phone: 617-919-6407
EMail: adamsdm@chop.edu
Layout table for additonal information
Responsible Party: Denise Martin Adams, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT02110069    
Other Study ID Numbers: SIR-DA-1202
1R01FD004363-01A1 ( U.S. FDA Grant/Contract )
2013-2339 ( Other Identifier: CCHMC IRB )
First Submitted: April 8, 2014
First Posted: April 10, 2014
Results First Submitted: December 11, 2020
Results First Posted: May 24, 2021
Last Update Posted: May 24, 2021