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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

  Hide Study Locations
Locations
United States, Alabama
Comprehensive Cancer Center at University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, United States, 36604
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Children's Hospital of Orange County
Orange, California, United States, 92868
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital Central California
Madera, California, United States, 93638-8762
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
Long Beach, California, United States, 90801
Kaiser Permanente Medical Center - Oakland
Sacramento, California, United States, 95825
Southern California Permanente Medical Group
Downey, California, United States, 90242-2814
Stanford Cancer Center at Stanford University Medical Center
Stanford, California, United States, 94305
Sutter Cancer Center
Sacramento, California, United States, 95816
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Connecticut
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
Farmington, Connecticut, United States, 06360-2875
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Florida
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, United States, 32803-1273
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States, 33407
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, United States, 33901
Sacred Heart Cancer Center at Sacred Heart Hospital
Pensacola, Florida, United States, 32504
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
Miami Children's Hospital
Miami, Florida, United States, 33155
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States, 33607
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
United States, Georgia
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
Savannah, Georgia, United States, 31403-3089
Emory University Hospital - Atlanta
Atlanta, Georgia, United States, 30322
MBCCOP-Medical College of Georgia Cancer Center
Augusta, Georgia, United States, 30912-3730
United States, Hawaii
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States, 95813
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61637
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62794-9620
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
St. Vincent Indianapolis Hospital
Indianapolis, Indiana, United States, 46260
United States, Iowa
Blank Children's Hospital
Des Moines, Iowa, United States, 50309
United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40232
United States, Louisiana
Children's Hospital of New Orleans
New Orleans, Louisiana, United States, 70118
Ochsner Cancer Institute at Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Maine
CancerCare of Maine at Eastern Maine Medial Center
Bangor, Maine, United States, 04401
Maine Children's Cancer Program
Scarborough, Maine, United States, 04074-9308
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
C.S. Mott Children's Hospital at University of Michigan
Ann Arbor, Michigan, United States, 48109-0238
CCOP - Kalamazoo
Kalamazoo, Michigan, United States, 49007-5341
Hurley Medical Center
Flint, Michigan, United States, 48503
Spectrum Health Cancer Care - Butterworth Campus
Grand Rapids, Michigan, United States, 49503-2560
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States, 48236
United States, Minnesota
Children's Hospital of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
Fairview University Medical Center - University Campus
Minneapolis, Minnesota, United States, 55455
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Cardinal Glennon Children's Hospital
St. Louis, Missouri, United States, 63104
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia, Missouri, United States, 65203
United States, New Jersey
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
New York Medical College
Valhalla, New York, United States, 10595
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Schneider Children's Hospital
New Hyde Park, New York, United States, 11040
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
Leo W. Jenkins Cancer Center at Pitt County Memorial Hospital
Greenville, North Carolina, United States, 27835-6028
United States, North Dakota
CCOP - MeritCare Hospital
Fargo, North Dakota, United States, 58122
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308-1062
Children's Medical Center - Dayton
Dayton, Ohio, United States, 45404-1815
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195-5217
Columbus Children's Hospital
Columbus, Ohio, United States, 43205-2696
Medical College of Ohio Cancer Institute
Toledo, Ohio, United States, 43614
Tod Children's Hospital - Forum Health
Youngstown, Ohio, United States, 44501
United States, Oklahoma
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Legacy Emanuel Hospital and Health Center & Children's Hospital
Portland, Oregon, United States, 97227
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-9786
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822-0001
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
United States, Rhode Island
Comprehensive Cancer Center at Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
Children's Hospital of Austin
Austin, Texas, United States, 78701
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104-9958
Covenant Children's Hospital
Lubbock, Texas, United States, 79410
Driscoll Children's Hospital
Corpus Christi, Texas, United States, 78466
Baylor University Medical Center - Houston
Houston, Texas, United States, 77030-2399
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113-1100
United States, Vermont
Fletcher Allen Health Care - University Health Center Campus
Burlington, Vermont, United States, 05405
United States, Virginia
Children's Hospital of the King's Daughters
Norfolk, Virginia, United States, 23507-1971
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22908
United States, Washington
Mary Bridge Children's Hospital and Health Center - Tacoma
Tacoma, Washington, United States, 98405
Madigan Army Medical Center - Tacoma
Tacoma, Washington, United States, 98431
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
United States, West Virginia
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
Huntington, West Virginia, United States, 25701
United States, Wisconsin
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States, 54307-3508
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Australia, New South Wales
Prince of Wales Private Hospital
Randwick, New South Wales, Australia, 2031
Westmead Institute for Cancer Research at Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Royal Children's Hospital
Herston, Brisbane, Queensland, Australia, 4029
Australia, South Australia
Women's and Children's Hospital
North Adelaide, South Australia, Australia, 5006
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T2T 5C7
Canada, British Columbia
Children's & Women's Hospital of British Columbia
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Ontario
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Canada, Quebec
Centre Hospitalier Universitaire de Quebec
Ste-Foy, Quebec, Canada, G1V 4G2
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada, H3H 1P3
Canada, Saskatchewan
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Switzerland
Swiss Pediatric Oncology Group Bern
Bern, Switzerland, 3010
Swiss Pediatric Oncology Group Lausanne
Lausanne, Switzerland, 1011
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 22, 2009