To Evaluate the Safety, Activity and Pharmacokinetics of Marqibo in Children and Adolescents With Refractory Cancer
- Marqibo(Registered Trademark) is a new anticancer drug. It combines Vincristine sulfate, which is a widely used anticancer drug, and packages it into a tiny fat bubble known as a liposome. The goal of this is to improve the drug's ability to destroy cancer cells and help reduce the potential side effects of treatment.
- Vincristine sulfate was originally developed from chemicals found in the periwinkle plant and acts against multiple types of malignant cancer. It is approved for multiple cancer types including solid tumors and blood cancers.
- Research has shown that Marqibo(Registered Trademark) is able to slow or stop the growth of cancer cells in some adults, both alone and in combination with other chemotherapy drugs, but more research is needed to determine its use in children.
- There has been one previous small study of Marqibo(Registered Trademark) in children. Although some anti-cancer activity was seen, side effects and optimal dosing were not fully determined.
- As is seen with standard Vincristine suflate, the most common side effect of Marqibo(Registered Trademark) involves the nervous system. It can cause numbness and tingling in the hands and feet. Symptoms commonly improve when the drug is discontinued or the dose is lowered.
- To determine the safety and efficacy of Marqibo as a treatment for children who have been diagnosed with certain types of malignant cancer that has not responded to standard treatment.
- Children and adolescents between 2 and 21 years of age who have been diagnosed with certain types of malignant cancer that has not responded to standard treatment.
- These cancer types include solids tumors, primary brain tumors, leukemias, and lymphomas....
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial to Evaluate the Safety, Activity and Pharmacokinetics of Marqibo(Registered Trademark) (Vincristine Sulfate Liposomes Injection) in Children and Adolescents With Refractory Cancer|
- Define the toxicity spectrum of Marqibo in children with cancer [ Time Frame: March, 2012 ] [ Designated as safety issue: Yes ]
- At the pediatric MTD of Marqibo, assess additional safety, tolerability and potential activity in subjects with refractory or relapsed ALL. [ Time Frame: March, 2012 ] [ Designated as safety issue: Yes ]
- Evaluate the plasma pharmacokinetics of Marqibo in children with cancer. [ Time Frame: March, 2012 ] [ Designated as safety issue: Yes ]
|Study Start Date:||September 2010|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
- The trial follows a rolling phase I design with 2 to 6 subjects per dose level and standard definitions of MTD and DLT. At the MTD, a total of 6 additional subjects with relapsed or refractory ALL will be evaluated.
- Detailed pharmacokinetic studies will be performed during the first treatment cycle
Marqibo® will be administered intravenously over 60 minutes (±10 minutes) every 7 days (±3 days) (Days 1, 8, 15, 22) for four doses (1 cycle). Cycles may be repeated every 28 days for a maximum of 6 cycles; additional cycles may be offered with evidence of acceptable toxicity and clinical benefit.
- Vincristine sulfate is a widely used antineoplastic agent of the alkaloid class of drugs derived from the periwinkle plant (Vinca rosea Linn.). It has activity against a wide number of malignancies. It is a cell-cycle-specific agent that arrests cell growth in the M-phase (metaphase) by binding specifically with tubulin and disrupting cell division. Its dose limiting toxicity (DLT) is virtually always neurological.
- Investigations over the past two decades have demonstrated that liposomal drug carriers are capable of increasing the therapeutic index of anticancer drugs by altering the drug s pharmacological behavior.
- Marqibo(Registered Trademark) is vincristine encapsulated in sphingomyelin/cholesterol (SM/CHOL) liposomes, developed to increase the activity of vincristine. It has been shown to have activity in Phase 2 studies in adults. Previous investigation of Marqibo(Registered Trademark) in children is limited. A small phase 2 study was conducted with dosing of 2.0mg/m2 every 14 days. The agent appeared to be well tolerated and some activity was seen, although data were quite limited.
- To define the maximum tolerated dose (MTD), toxicity profile, dose-limiting toxicities, and pharmacokinetics in children and adolescents with solid tumors or hematologic malignancies receiving weekly intravenous doses of Marqibo(Registered Trademark).
- To define the tolerability and potential activity of Marqibo(Registered Trademark) in children and adolescents with relapsed or refractory acute lymphoblastic leukemia (ALL) at the pediatric MTD.
- Children and adolescents (greater than or equal to 2 years and < 21 years of age) with histologically confirmed relapsed or refractory malignant disease that is measurable or evaluable.
- Marqibo(Registered Trademark) will be administered intravenously over 60 minutes (+ or -10 minutes) every 7 days (+ or - 3 days) (Days 1, 8, 15, 22) for four doses (1 cycle). Cycles may be repeated every 28 days for a maximum of 6 cycles; additional cycles may be offered with evidence of acceptable toxicity and clinical benefit.
- The trial follows a standard phase I design with 3 to 6 subjects per dose level and standard definitions of MTD and DLT. At the MTD, a total of 6 additional subjects with relapsed or refractory ALL will be evaluated.
- Detailed pharmacokinetic studies will be performed during the first treatment cycle.
|Contact: Alan S Wayne, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator: Alan Wayne, M.D.|
|Sub-Investigator: Cindy Delbrook, B.S.N.|
|Sub-Investigator: Kelly Richards, RN, MSN|
|Principal Investigator:||Allen Wayne||National Cancer Institute (NCI)|