To Evaluate the Safety, Activity and Pharmacokinetics of Marqibo in Children and Adolescents With Refractory Cancer
Condition: Sarcoma; Neuroblastoma; Wilms Tumor; Leukemia; Lymphoma; Brain Tumors
MeSH terms: Neoplasms; Sarcoma; Brain Neoplasms; Neuroblastoma; Wilms Tumor
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

        -  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.

      Objectives:

      - 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.

      Eligibility:

        -  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.
    

Detailed description: 
      BACKGROUND

        -  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.

      OBJECTIVES

        -  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.

      ELIGIBILITY

      - 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.

      DESIGN

        -  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.
    

Intervention name(s): Marqibo
Intervention type(s): Drug
Intervention description(s): Marqibo® intravenously (IV) over 60 minutes (+ 10 minutes) every 7 days (+ 3 days) for 4 consecutive weeks (day 1, 8, 15, 22) for a 28-day treatment cycle
Other intervention name(s): Vincristin Sulfate Liposomal Injection
Intervention MeSH terms: Vincristine
Intervention model: Sequential Assignment
Intervention model description: Phase 1 Trial to Evaluate the Safety, Activity and Pharmacokinetics of Marqibo® (Vincristine Sulphate Liposomes Injection) in Children and Adolescents with Refractory Cancer
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hematologic Malignancies; Vincristine Sulfate; Maximum Tolerated Dose; Pharmacokinetics; Solid Tumors; Cancer; Pediatrics; Sarcoma; Wilms Tumor; Leukemia; Lymphoma; Brain Tumor