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Topotecan in Treating Children With Meningeal Cancer That Has Not Responded to Previous Treatment
This study has been completed.
First Received: June 2, 2000   Last Updated: February 14, 2009   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005811
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase II trial is studying how well topotecan works in treating children with meningeal cancer that has not responded to previous treatment.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Leukemia
Lymphoma
Metastatic Cancer
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: topotecan hydrochloride
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: Phase II Study of Intrathecal Topotecan (NSC #609699) in Patients With Refractory Meningeal Malignancies

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Therapeutic activity [ Designated as safety issue: No ]
  • Safety and toxicity [ Designated as safety issue: Yes ]
  • Concentration of matrix metalloproteinases in the CSF [ Designated as safety issue: No ]

Estimated Enrollment: 77
Study Start Date: April 2000
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Determine the therapeutic activity of intrathecal topotecan, in terms of response rate and time to CNS progression, in pediatric patients with recurrent or refractory neoplastic meningitis.
  • Determine the safety and toxicity of this regimen in these patients.
  • Evaluate the concentration of matrix metalloproteinases (MMPs) in the CSF of these patients.

OUTLINE: Patients are stratified according to disease type (acute lymphoblastic leukemia vs other leukemia/lymphoma vs medulloblastoma vs other solid tumors). (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04)

  • Induction: Patients receive topotecan intrathecally (IT) over 5 minutes twice weekly for 6 weeks.
  • Consolidation: Beginning 1 week after completion of induction, patients receive topotecan IT over 5 minutes weekly for 4 weeks in the absence of disease progression or unacceptable toxicity.
  • Maintenance: Beginning 2 weeks after completion of consolidation, patients receive topotecan IT over 5 minutes twice monthly for 4 months and then monthly through year 1.

Patients are followed monthly for 3 months, every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 14-77 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically proven refractory leukemia, lymphoma, or other solid tumor that has overt meningeal involvement (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04)

    • Definition of meningeal disease:

      • Leukemia/lymphoma (including acute lymphoblastic leukemia)

        • CSF cell count greater than 5/mm^3 AND evidence of blast cells on cytospin preparation or by cytology
        • Refractory to conventional therapy, including radiotherapy (i.e., in second or greater relapse)
        • No concurrent bone marrow relapse
      • Solid tumors (including medulloblastoma)

        • Presence of tumor cells on cytospin preparation or cytology OR presence of meningeal disease on MRI scans
  • No clinical evidence of obstructive hydrocephalus or compartmentalization of CSF flow as documented by radioisotope indium In 111 or technetium Tc 99 DTPA flow study

    • If CSF flow block is demonstrated, focal radiotherapy must be administered to site of block to restore flow and a repeat CSF flow study must show clearing of blockage
  • No ventriculoperitoneal or ventriculoatrial shunt unless:

    • Patient is shunt independent and there is evidence that the shunt is nonfunctional
    • CSF flow study demonstrates normal flow
  • No impending cord compression, CNS involvement requiring local radiotherapy (e.g., optic nerve), or isolated bulky ventricular or leptomeningeal based lesions

PATIENT CHARACTERISTICS:

Age:

  • 1 to 21

Performance status:

  • Lansky 50-100% (age 10 and under)
  • Karnofsky 50-100% (over age 10)

Life expectancy:

  • At least 8 weeks

Hematopoietic:

  • Platelet count greater than 40,000/mm^3 (transfusions allowed)

Hepatic:

  • Bilirubin less than 2.0 mg/dL
  • SGPT less than 5 times normal

Renal:

  • Creatinine less than 1.5 mg/dL
  • Electrolytes, calcium, and phosphorus normal

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No significant illness (e.g., uncontrolled infection, except HIV [i.e., AIDS-related lymphomatous meningitis])

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Prior immunotherapy allowed and recovered

Chemotherapy:

  • At least 3 weeks since systemic CNS directed chemotherapy (6 weeks for nitrosoureas) and recovered
  • At least 1 week since prior intrathecal (IT) chemotherapy (2 weeks for cytarabine [liposomal])
  • No prior IT chemotherapy on days -14 to -7 before study entry unless evidence of disease progression (e.g., increasing WBC and percentage blasts in patients with leukemia/lymphoma or increased leptomeningeal enhancements in patients with solid tumors) (Recurrent CNS acute lymphoblastic leukemia stratum only open to accrual as of 11/30/04)
  • Concurrent chemotherapy to control systemic disease or bulk CNS disease allowed if the systemic chemotherapy is not a phase I study agent that significantly penetrates the CSF (e.g., high-dose systemic methotrexate [greater than 1 g/m^2], thiotepa, high-dose cytarabine, temozolomide, IV mercaptopurine, nitrosourea, or topotecan) or an agent known to have serious unpredictable CNS side effects

Endocrine therapy:

  • Concurrent dexamethasone or prednisone allowed if part of a systemic chemotherapy regimen

Radiotherapy:

  • See Disease Characteristics
  • At least 8 weeks since prior cranial irradiation and recovered
  • No concurrent whole brain or craniospinal irradiation

Surgery:

  • Not specified

Other:

  • At least 7 days since prior investigational drug

    • Time period should be extended if patient has received any investigational agent that is known to have delayed toxic effects after 7 days or a prolonged half-life
  • No other concurrent investigational agents
  • No concurrent therapy (IT or systemic) for leptomeningeal disease
  • No other concurrent systemic agents that significantly penetrate the blood-brain barrier
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005811

  Show 110 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Susan M. Blaney, MD Texas Children's Cancer Center
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000067813, COG-P9962, POG-9962, CCG-P9962, NCI-01-C-0123
Study First Received: June 2, 2000
Last Updated: February 14, 2009
ClinicalTrials.gov Identifier: NCT00005811     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute lymphoblastic leukemia
recurrent childhood lymphoblastic lymphoma
recurrent childhood acute myeloid leukemia
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
unspecified childhood solid tumor, protocol specific
recurrent/refractory childhood Hodgkin lymphoma
leptomeningeal metastases
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
AIDS-related diffuse large cell lymphoma
AIDS-related immunoblastic large cell lymphoma
AIDS-related small noncleaved cell lymphoma
HIV-associated Hodgkin lymphoma
AIDS-related diffuse mixed cell lymphoma
AIDS-related diffuse small cleaved cell lymphoma
AIDS-related lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
recurrent childhood medulloblastoma

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Immunoproliferative Disorders
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Nervous System Diseases
Enzyme Inhibitors
Central Nervous System Neoplasms
Pharmacologic Actions
Leukemia
Lymphatic Diseases
Neoplasms
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Therapeutic Uses
Neoplasm Metastasis
Topotecan
Lymphoproliferative Disorders
Lymphoma
Nervous System Neoplasms

ClinicalTrials.gov processed this record on November 30, 2009