Topotecan Hydrochloride in Treating Children With Meningeal Cancer That Has Not Responded to Previous Treatment

February 20, 2013 updated by: National Cancer Institute (NCI)

A Phase II Study of Intrathecal Topotecan (NSC #609699) in Patients With Refractory Meningeal Malignancies

Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. This phase II trial is studying how well topotecan hydrochloride works in treating children with meningeal cancer that has not responded to previous treatment

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the therapeutic activity of intrathecal topotecan, in terms of response rate and time to central nervous system (CNS) progression, in pediatric patients with recurrent or refractory neoplastic meningitis.

II. Determine the safety and toxicity of this regimen in these patients. III. Evaluate the concentration of matrix metalloproteinases (MMPs) in the cerebrospinal fluid (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 hydrochloride intrathecally (IT) over 5 minutes twice weekly for 6 weeks.

CONSOLIDATION: Beginning 1 week after completion of induction, patients receive topotecan hydrochloride 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 hydrochloride IT over 5 minutes twice monthly for 4 months and then monthly through year 1.

After completion of study treatment, patients are followed up 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.

Study Type

Interventional

Enrollment (Actual)

77

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Arcadia, California, United States, 91006-3776
        • Children's Oncology Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically proven refractory leukemia, lymphoma, or other solid tumor thathas 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 oncytospin 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 ofmeningeal disease on MRI scans

  • No clinical evidence of obstructive hydrocephalus or compartmentalization ofCSF flow as documented by radioisotope indium In 111 or technetium Tc 99 DTPAflow study

    • If CSF flow block is demonstrated, focal radiotherapy must be administered tosite 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 basedlesions
  • Performance status - Lansky 50-100% (age 10 and under)
  • Performance status - Karnofsky 50-100% (over age 10)
  • At least 8 weeks
  • Platelet count greater than 40,000/mm^3 (transfusions allowed)
  • Bilirubin less than 2.0 mg/dL
  • SGPT less than 5 times normal
  • Creatinine less than 1.5 mg/dL
  • Electrolytes, calcium, and phosphorus normal
  • 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 immunotherapy allowed and recovered
  • 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
  • Concurrent dexamethasone or prednisone allowed if part of a systemic chemotherapy regimen
  • See Disease Characteristics
  • At least 8 weeks since prior cranial irradiation and recovered
  • No concurrent whole brain or craniospinal irradiation

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (topotecan hydrochloride)

INDUCTION: Patients receive topotecan hydrochloride IT over 5 minutes twice weekly for 6 weeks.

CONSOLIDATION: Beginning 1 week after completion of induction, patients receive topotecan hydrochloride 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 hydrochloride IT over 5 minutes twice monthly for 4 months and then monthly through year 1.
Other: laboratory biomarker analysis
Correlative studies
Drug: topotecan hydrochloride
Given IT
Other Names:
  • Hycamtin
  • SKF S-104864-A
  • hycamptamine
  • TOPO

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
For the leukemia and lymphoma patients, an objective response rate, defined to be the proportion of Complete Responses of less than 0.10
Time Frame: Up to 54 months
Up to 54 months
For the patients with solid tumors, a proportion of patients who do not experience an event, defined to be death, progressive disease, relapse, or second malignancy of less than 0.3
Time Frame: Up to 54 months
Up to 54 months
Safety and toxicity
Time Frame: Up to 54 months
Up to 54 months
Concentration of matrix metalloproteinases in the CSF
Time Frame: Up to 54 months
Up to 54 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Susan Blaney, Children's Oncology Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2000

Primary Completion (Actual)

April 1, 2006

Study Completion (Actual)

February 1, 2009

Study Registration Dates

First Submitted

June 2, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

February 21, 2013

Last Update Submitted That Met QC Criteria

February 20, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-01848
  • U10CA098543 (U.S. NIH Grant/Contract)
  • P9962
  • CDR0000067813 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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