NCT00112619

Brief Summary

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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at P25-P50 for phase_1

Geographic Reach
1 country

11 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 2, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 3, 2005

Completed
2 months until next milestone

Study Start

First participant enrolled

August 1, 2005

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2010

Completed
Last Updated

June 30, 2011

Status Verified

June 1, 2011

Enrollment Period

5 years

First QC Date

June 2, 2005

Last Update Submit

June 29, 2011

Conditions

Brain and Central Nervous System TumorsCarcinoma of Unknown PrimaryLeukemiaLymphomaUnspecified Childhood Solid Tumor, Protocol Specific

Keywords

AIDS-related diffuse large cell lymphomaAIDS-related diffuse mixed cell lymphomaAIDS-related diffuse small cleaved cell lymphomaAIDS-related immunoblastic large cell lymphomaAIDS-related lymphoblastic lymphomaAIDS-related peripheral/systemic lymphomaAIDS-related primary CNS lymphomaAIDS-related small noncleaved cell lymphomaHIV-associated Hodgkin lymphomastage IV childhood Hodgkin lymphomastage IV childhood large cell lymphomastage IV childhood lymphoblastic lymphomastage IV childhood small noncleaved cell lymphomaprimary central nervous system non-Hodgkin lymphomaprimary central nervous system Hodgkin lymphomarecurrent childhood acute lymphoblastic leukemiarecurrent childhood acute myeloid leukemiaunspecified childhood solid tumor, protocol specificchildhood grade I meningiomachildhood grade II meningiomachildhood grade III meningiomarecurrent childhood cerebellar astrocytomarecurrent childhood cerebral astrocytomachildhood high-grade cerebral astrocytomachildhood low-grade cerebral astrocytomachildhood choroid plexus tumorchildhood craniopharyngiomachildhood infratentorial ependymomachildhood supratentorial ependymomarecurrent childhood ependymomarecurrent childhood medulloblastomachildhood oligodendrogliomarecurrent childhood supratentorial primitive neuroectodermal tumorleptomeningeal metastasesrecurrent carcinoma of unknown primarychildhood central nervous system germ cell tumorchildhood chronic myelogenous leukemiajuvenile myelomonocytic leukemiarecurrent/refractory childhood Hodgkin lymphomarecurrent childhood grade III lymphomatoid granulomatosisrecurrent childhood visual pathway and hypothalamic gliomachildhood atypical teratoid/rhabdoid tumorrecurrent childhood large cell lymphomarecurrent childhood lymphoblastic lymphomarecurrent childhood small noncleaved cell lymphomarelapsing chronic myelogenous leukemiarecurrent childhood pineoblastomarecurrent childhood subependymal giant cell astrocytomameningeal leukemiasecondary central nervous system Hodgkin lymphomasecondary central nervous system non-Hodgkin lymphoma

Outcome Measures

Primary Outcomes (3)

  • Estimate the maximum tolerated dose of intraventricular topotecan on this schedule

    First 14 days of therapy

  • Number of patients with dose-limiting toxicity

    First 14 days of therapy

  • Estimate the dose of intraventricular topotecan that will result in cerebrospinal fluid lactone concentrations exceeding 1 ng/mL for at least 8 hours after an intrathecal injection

    Day 1 of Week 1

Secondary Outcomes (3)

  • Number of patients with objective documentation of tumor response to intraventricular topotecan

    Weeks 5, 11 and then every 12 weeks until off study

  • Pharmacokinetics

    Day 1 of Week 1

  • Correlation of imaging parameters with tumor response

    Pre-treatment, week 5, week 11, and then every 12 weeks until off study

Interventions

topotecan hydrochlorideDRUG

Participants receive intraventricular topotecan, .2 mg, administered via an indwelling ventricular reservoir daily for 5 consecutive days during weeks 1 and 3 of the first four weeks of therapy (induction), during weeks 5 and 8 of the next 6 weeks of therapy (consolidation), and during weeks 11, 15, 19, 23, 27, 31, 35, 39, 43, 47, and 51 (maintenance therapy).

Also known as: Hycamptin

Eligibility Criteria

Age3 Years - 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)
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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (11)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010-2970, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Dan L. Duncan Cancer Center at Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Central Nervous System NeoplasmsNeoplasms, Unknown PrimaryLeukemiaLymphomaDendritic Cell Sarcoma, InterdigitatingBurkitt LymphomaPrecursor Cell Lymphoblastic Leukemia-LymphomaAstrocytomaChoroid Plexus NeoplasmsFamilial ependymomaMedulloblastomaOligodendrogliomaMeningeal CarcinomatosisLeukemia, Myelomonocytic, JuvenileRecurrenceOptic Nerve GliomaRhabdoid Tumor

Interventions

Topotecan

Condition Hierarchy (Ancestors)

Nervous System NeoplasmsNeoplasms by SiteNeoplasmsNervous System DiseasesNeoplasm MetastasisNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms by Histologic TypeHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesHistiocytic Disorders, MalignantHistiocytosisEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphoma, Non-HodgkinLeukemia, LymphoidGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueCerebral Ventricle NeoplasmsBrain NeoplasmsBrain DiseasesCentral Nervous System DiseasesNeuroectodermal Tumors, PrimitiveMeningeal NeoplasmsLeukemia, MyeloidMyelodysplastic-Myeloproliferative DiseasesBone Marrow DiseasesDisease AttributesOptic Nerve NeoplasmsCranial Nerve NeoplasmsPeripheral Nervous System NeoplasmsCranial Nerve DiseasesOptic Nerve DiseasesEye DiseasesNeoplasms, Complex and Mixed

Intervention Hierarchy (Ancestors)

CamptothecinAlkaloidsHeterocyclic Compounds

Study Officials

  • Susan M. Blaney, MD

    Baylor College of Medicine

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NETWORK

Study Record Dates

First Submitted

June 2, 2005

First Posted

June 3, 2005

Study Start

August 1, 2005

Primary Completion

August 1, 2010

Last Updated

June 30, 2011

Record last verified: 2011-06

Locations

US(11)