To Evaluate the Safety, Activity and Pharmacokinetics of Marqibo in Children and Adolescents With Refractory Cancer

NCT01222780 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 100220IND 59,056
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sarcoma; Neuroblastoma; Wilms Tumor; Leukemia; Lymphoma; Brain Tumors

Keywords

Hematologic Malignancies; Vincristine Sulfate; Maximum Tolerated Dose; Pharmacokinetics; Solid Tumors; Cancer; Pediatrics; Sarcoma; Wilms Tumor; Leukemia; Lymphoma; Brain Tumor

Outcome Measures

Primary Outcomes (3)

• Define the toxicity spectrum of Marqibo in children with cancer

  Toxicity was graded according to the version 4.0 of the NCI Common Toxicity Criteria (CTCAE v4.0).

  up to 48 weeks

• Determine of Marqibo® administered as a 60 minute intravenous infusion weekly (every 28 days constitute 1 cycle), in children and adolescents with refractory solid tumors and hematologic malignancies.

  The MTD was defined as the dose level immediately below the dose level at which ≥2 subjects in a cohort of 2 to 6 subjects experienced a DLT.

  up to 48 weeks

• Determine dose limiting toxicities (DLT) of Marqibo® administered as a 60 minute intravenous infusion weekly (every 28 days constitute 1 cycle), in children and adolescents with refractory solid tumors and hematologic malignancies.

  DLT was graded according to the version 4.0 of the NCI Common Toxicity Criteria (CTCAE v4.0). Adverse events (AEs) that were considered disease-related (not suspected of relationship to Marqibo) were not considered dose-limiting toxicities. Only those AEs deemed suspected of a relationship to Marqibo were used in the definition of DLT.

  up to 48 weeks

Secondary Outcomes (1)

• Evaluate the plasma pharmacokinetics of Marqibo in children with cancer.

  28 days

Study Arms (1)

Marqibo

EXPERIMENTAL

Marqibo® (Vincristine sulfate liposomal) 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. * 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

Drug: Marqibo

Interventions

Marqibo DRUG

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

Also known as: Vincristin Sulfate Liposomal Injection

Marqibo

Eligibility Criteria

• Age: 2 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• AGE: Subjects must be greater than or equal to 2 years and \< 21 years of age.
• DIAGNOSIS: Histologically confirmed solid tumors, which may include but are not limited to rhabdomyosarcoma and other soft tissue sarcomas, Ewing sarcoma family of tumors, osteosarcoma, neuroblastoma, Wilms tumor, hepatic tumors, germ cell tumors, and primary brain tumors. In subjects with brain stem or optic gliomas the requirement for histological confirmation may be waived.
• Histologically confirmed diagnosis of hematologic malignancy, including but not limited to acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), Hodgkin's lymphoma, and non-Hodgkin's lymphoma (NHL). Isolated CNS or testicular disease is NOT allowed.
• MEASURABLE/EVALUABLE DISEASE: Subjects must have measurable or evaluable malignant disease.
• PRIOR THERAPY:
• The subject s cancer must have relapsed after or failed to respond to frontline curative therapy and there must not be other potentially curative treatment options available to that subject at the time of study entry.
• Subjects must have had their last doses of therapy prior to receiving the first dose of the investigational agent as follows (provided there is complete recovery from any acute toxic effects of such):
• Chemotherapy at least 14 days (6 weeks for nitrosoureas);
• Radiation at least 21 days;
• Any investigational cancer therapy or monoclonal antibody therapy (e.g., rituximab) at least 30 days.
• Exceptions to these requirements:
• Intrathecal chemotherapy: There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such.
• Radiation therapy: There is no time restriction in regard to prior radiation provided the volume of bone marrow treated is less than 10% and that there is measurable disease outside the radiation port.
• Patients receiving corticosteroids or hydroxyurea are eligible provided all of the following conditions are met.
• Patients with CNS tumors who are managed with steroids are eligible if they are on a stable or decreasing dose of steroids and have no worsening neurologic deficits for greater than or equal to 7 days prior to registration.

You may not qualify if:

• Clinically significant unrelated systemic illness, such as uncontrolled serious infection or organ dysfunction, which in the judgment of protocol investigators would compromise the subject s ability to tolerate the investigational agent or interfere with the study procedures or results. This includes any condition or circumstance that in the opinion of the investigator would significantly interfere with the subject s protocol compliance and put the subject at increased risk.
• CNS leukemia or lymphoma as manifested by any of the following:
• CSF WBC \> 5/microL and confirmation of CSF blasts.
• Cranial neuropathies deemed secondary to underlying malignancy
• CT or MRI scan evidence.
• Neutrophil count \< 1,000/microL or platelet count of \< 50,000/microL (except for the expanded ALL cohort, where there is no blood count requirement).
• Pregnant or breast-feeding females are excluded because Marqibo(Registered Trademark) may be harmful to the developing fetus or nursing child.
• Currently receiving other investigational agents.
• History of previously receiving Marqibo(Registered Trademark).
• History of allergic reactions or serious adverse events attributed to compounds of similar chemical or biologic composition to vincristine or components of Marqibo(Registered Trademark) (vincristine sulfate injection, sphingomyelin/cholesterol liposomes, sodium phosphate injection).
• Are eligible for stem cell transplantation. This implies that a suitable donor is readily available, that the primary oncology team and Principal Investigator recommend this as a preferred treatment option at the time of protocol evaluation, and that the subject is willing to undergo stem cell transplantation.
• Presence of preexisting Grade 2 or greater sensory or motor neuropathy.
• History of persistent greater than or equal to Grade 2 active neurologic disorders unrelated to chemotherapy.
• Positive for human immunodeficiency virus (HIV) due to the increased risk of complications.

Sponsors & Collaborators

• Acrotech Biopharma Inc.: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Ross JA, Olshan AF. Pediatric cancer in the United States: the Children's Oncology Group Epidemiology Research Program. Cancer Epidemiol Biomarkers Prev. 2004 Oct;13(10):1552-4. No abstract available.

  PMID: 15466968 BACKGROUND

• Linabery AM, Ross JA. Trends in childhood cancer incidence in the U.S. (1992-2004). Cancer. 2008 Jan 15;112(2):416-32. doi: 10.1002/cncr.23169.

  PMID: 18074355 BACKGROUND

• Chonn A, Cullis PR. Recent advances in liposomal drug-delivery systems. Curr Opin Biotechnol. 1995 Dec;6(6):698-708. doi: 10.1016/0958-1669(95)80115-4.

  PMID: 8527843 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma; Neuroblastoma; Wilms Tumor; Leukemia; Lymphoma; Brain Neoplasms; Hematologic Neoplasms; Neoplasms

Interventions

Vincristine

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Allen Wayne

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1 Trial to Evaluate the Safety, Activity and Pharmacokinetics of Marqibo® (Vincristine Sulphate Liposomes Injection) in Children and Adolescents with Refractory Cancer

Study Record Dates

• First Submitted: October 15, 2010
• First Posted: October 18, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 18, 2020

Record last verified: 2020-01

Locations

US (1)