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Topotecan in Treating Young Patients With Neoplastic Meningitis Due to Leukemia, Lymphoma, or Solid Tumors
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), April 2008
First Received: June 2, 2005   Last Updated: January 6, 2009   History of Changes
Sponsors and Collaborators: Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00112619
  Purpose

RATIONALE: Drugs used in chemotherapy, such as topotecan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects, best way to give, and best dose of topotecan when given by intraventricular infusion in treating young patients with neoplastic meningitis due to leukemia, lymphoma, or solid tumors.


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

Study Type: Interventional
Study Design: Supportive Care
Official Title: A Phase I Pharmacokinetic Optimal Dosing Study of Intraventricular Topotecan for Children With Neoplastic Meningitis

Resource links provided by NLM:


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

Estimated Enrollment: 49
Study Start Date: August 2005
Estimated Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose (MTD) of intraventricular topotecan in young patients with neoplastic meningitis secondary to leukemia, lymphoma, or solid tumors.
  • Determine the toxic effects and dose-limiting toxicity of this drug in these patients.
  • Determine whether the MTD of this drug is also the pharmacokinetic optimal dose, defined by the topotecan lactone concentration in the cerebral spinal fluid (CSF), in these patients.

Secondary

  • Determine, preliminarily, the antitumor activity of this drug in these patients.
  • Determine the pharmacokinetics of this drug in the CSF of these patients.
  • Correlate observed effects of post-treatment central review imaging (if feasible) with response to this drug in these patients.

OUTLINE: This is a non-randomized, dose-escalation, multicenter study.

  • Induction therapy (weeks 1-4): Patients receive topotecan intraventricularly* over 5 minutes on days 1-5 in weeks 1 and 3. Patients then proceed to consolidation therapy in week 5. NOTE: *Patients who are willing, receive 1 intralumbar (instead of intraventricular) dose of topotecan on day

    1 of week 3 only.

  • Consolidation therapy (weeks 5-10): Patients receive topotecan intraventricularly on days 1-5 in weeks 5 and 8. Patients then proceed to maintenance therapy in week 11.
  • Maintenance therapy (weeks 11-54): Patients receive topotecan intraventricularly on days 1-5 in weeks 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, and 51. Cohorts of 3-6 patients receive escalating doses of intraventricular topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, the cohort is expanded to 25 patients and the MTD is declared the pharmacokinetic optimal dose provided 23 of 25 patients treated at the MTD achieve the target pharmacokinetic parameter.

PROJECTED ACCRUAL: A total of 28-49 patients will be accrued for this study within 9-24 months.

  Eligibility

Ages Eligible for Study:   3 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of neoplastic meningitis secondary to leukemia, lymphoma (including AIDS-related lymphoma), or solid tumor (including primary CNS tumors or carcinomas of unknown primary site), defined by 1 of the following criteria:

    • Cerebral spinal fluid (CSF) cell count > 5/μL AND evidence of blast cells on cytospin or by cytology (for patients with leukemia or lymphoma)
    • Presence of tumor cells on cytospin or cytology OR unequivocal presence of meningeal disease by MRI (for patients with solid tumor)
  • No conventional therapy for neoplastic meningitis exists

    • Patients with CNS leukemia or lymphoma must be refractory to conventional therapy, including radiotherapy (i.e., second or greater relapse)
  • Patients with CNS leukemia or lymphoma must have had a negative bone marrow aspiration within the past 2 weeks
  • No clinical evidence of obstructive hydrocephalus
  • No compartmentalization of CSF flow by radioisotope indium In 111 or technetium Tc 99 DTPA flow study
  • No ventriculoperitoneal or ventriculoatrial shunt unless patient is completely shunt-independent
  • No impending spinal cord compression or other CNS involvement (e.g., acute visual loss secondary to optic nerve involvement) requiring emergent local radiotherapy

PATIENT CHARACTERISTICS:

Age

  • 3 to 21

Performance status

  • Lansky 60-100% (≤ 16 years of age) OR
  • Karnofsky 60-100% (> 16 years of age)

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Calcium ≥ 7 mg/dL

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Sodium 125-150 mmol/L
  • Magnesium ≥ 0.7 mmol/L
  • Must have or be willing to have an intraventricular access device (i.e., Ommaya reservoir)
  • No uncontrolled infection

    • HIV-positive patients with AIDS-related lymphomatous meningitis are eligible
  • No other significant uncontrolled systemic medical illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Recovered from prior biologic therapy or immunotherapy

Chemotherapy

  • Recovered from prior chemotherapy
  • At least 1 week since prior intra-colony stimulating factory (CSF) chemotherapy (2 weeks for liposomal cytarabine)
  • At least 3 weeks since prior systemic chemotherapy for leptomeningeal disease
  • Concurrent systemic chemotherapy to control systemic disease or bulk CNS disease allowed provided the systemic chemotherapy is not an investigational agent OR any of the following:

    • High-dose (> 1 g/m^2) methotrexate
    • High-dose (> 1 g/m^2) cytarabine
    • Fluorouracil
    • Capecitabine
    • Thiotepa
    • Nitrosoureas
    • Topotecan

Endocrine therapy

  • Not specified

Radiotherapy

  • See Disease Characteristics
  • At least 8 weeks since prior craniospinal radiotherapy and recovered
  • No concurrent CNS radiotherapy

    • Concurrent radiotherapy to extra-CNS sites (e.g., painful bone metastases not in the craniospinal axis) allowed

Surgery

  • Not specified

Other

  • More than 2 weeks since prior and no other concurrent investigational agents
  • No other concurrent intra-CSF or systemic therapy for leptomeningeal disease
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00112619

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi     877-827-3222        
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010-2970
Contact: Clinical Trials Office - Children's National Medical Center     202-884-2549        
United States, Illinois
Children's Memorial Hospital - Chicago Recruiting
Chicago, Illinois, United States, 60614
Contact: Stewart Goldman, MD     773-880-4562        
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center     888-NCI-1937        
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Mark W. Kieran, MD, PhD     617-632-4907        
United States, North Carolina
Duke Comprehensive Cancer Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Clinical Trials Office - Duke Comprehensive Cancer Center     888-275-3853        
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104-4318
Contact: Peter C. Phillips, MD     215-590-2107        
Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Clinical Trials Office - Children's Hospital of Pittsburgh     412-692-5573        
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: James M. Boyett, PhD     901-495-4896        
United States, Texas
Dan L. Duncan Cancer Center at Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Trials Office - Dan L. Duncan Cancer Center at Baylor     713-798-1297        
United States, Washington
Children's Hospital and Regional Medical Center - Seattle Recruiting
Seattle, Washington, United States, 98105
Contact: Jeffrey R. Geyer, MD     206-987-6664        
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
Investigators
Investigator: Stacie Stapleton, MD Baylor College of Medicine
Study Chair: Susan M. Blaney, MD Baylor College of Medicine
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000430504, PBTC-019
Study First Received: June 2, 2005
Last Updated: January 6, 2009
ClinicalTrials.gov Identifier: NCT00112619     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
AIDS-related diffuse large cell lymphoma
AIDS-related diffuse mixed cell lymphoma
AIDS-related diffuse small cleaved cell lymphoma
AIDS-related immunoblastic large cell lymphoma
AIDS-related lymphoblastic lymphoma
AIDS-related peripheral/systemic lymphoma
AIDS-related primary CNS lymphoma
AIDS-related small noncleaved cell lymphoma
HIV-associated Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
stage IV childhood large cell lymphoma
stage IV childhood lymphoblastic lymphoma
stage IV childhood small noncleaved cell lymphoma
primary central nervous system lymphoma
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
unspecified childhood solid tumor, protocol specific
childhood grade I meningioma
childhood grade II meningioma
childhood grade III meningioma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
childhood high-grade cerebral astrocytoma
childhood low-grade cerebral astrocytoma
childhood choroid plexus tumor
childhood craniopharyngioma
childhood infratentorial ependymoma
childhood supratentorial ependymoma
recurrent childhood ependymoma
recurrent childhood medulloblastoma

Study placed in the following topic categories:
Neuroectodermal Tumors, Primitive
Central Nervous System Neoplasms
Acute Myelocytic Leukemia
Neoplasm Metastasis
Neuroepithelioma
Glioma
Hodgkin Disease
Nervous System Neoplasms
Lymphoma, Large B-Cell, Diffuse
Neoplasms, Unknown Primary
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Astrocytoma
Acquired Immunodeficiency Syndrome
Juvenile Myelomonocytic Leukemia
Leukemia, Myeloid
Carcinoma
Neuroectodermal Tumors
HIV Infections
Chronic Myelogenous Leukemia
Topotecan
Lymphoma, Non-Hodgkin
Neoplasms, Glandular and Epithelial
Acute Lymphoblastic Leukemia, Childhood
Choroid Plexus Neoplasms
Leukemia, Lymphoid
Rhabdoid Tumor
Hodgkin Lymphoma, Childhood
Central Nervous System Lymphoma, Primary
Leukemia, Myeloid, Acute

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

ClinicalTrials.gov processed this record on August 30, 2009