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Topotecan in Treating Young Patients With Neoplastic Meningitis Due to Leukemia, Lymphoma, or Solid Tumors

29. juni 2011 opdateret af: Pediatric Brain Tumor Consortium

A Phase I Pharmacokinetic Optimal Dosing Study of Intraventricular Topotecan for Children With Neoplastic Meningitis

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.

Studieoversigt

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

19

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • California
      • San Francisco, California, Forenede Stater, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • District of Columbia
      • Washington, District of Columbia, Forenede Stater, 20010-2970
        • Children's National Medical Center
    • Illinois
      • Chicago, Illinois, Forenede Stater, 60614
        • Children's Memorial Hospital - Chicago
    • Maryland
      • Bethesda, Maryland, Forenede Stater, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02115
        • Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
    • North Carolina
      • Durham, North Carolina, Forenede Stater, 27710
        • Duke Comprehensive Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater, 19104-4318
        • Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, Forenede Stater, 15213
        • Children's Hospital of Pittsburgh
    • Tennessee
      • Memphis, Tennessee, Forenede Stater, 38105
        • St. Jude Children's Research Hospital
    • Texas
      • Houston, Texas, Forenede Stater, 77030
        • Dan L. Duncan Cancer Center at Baylor College of Medicine
    • Washington
      • Seattle, Washington, Forenede Stater, 98105
        • Children's Hospital and Regional Medical Center - Seattle

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

3 år til 21 år (Barn, Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
Estimate the maximum tolerated dose of intraventricular topotecan on this schedule
Tidsramme: First 14 days of therapy
First 14 days of therapy
Number of patients with dose-limiting toxicity
Tidsramme: First 14 days of therapy
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
Tidsramme: Day 1 of Week 1
Day 1 of Week 1

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of patients with objective documentation of tumor response to intraventricular topotecan
Tidsramme: Weeks 5, 11 and then every 12 weeks until off study
MRI of the brain and spine is obtained pre-consolidation, pre-maintenance, and then every 12 weeks in maintenance.
Weeks 5, 11 and then every 12 weeks until off study
Pharmacokinetics
Tidsramme: Day 1 of Week 1
The cerebrospinal fluid (CSF) concentration-time profile for topotecan after intrathecal CSF administration will be modeled from the CSF samples collected on day 1 of week 1. Individual pharmacokinetic parameters estimated will include volume of central compartment, elimination rate constant, half-life, and clearance.
Day 1 of Week 1
Correlation of imaging parameters with tumor response
Tidsramme: Pre-treatment, week 5, week 11, and then every 12 weeks until off study
MRI scans of the brain and spine is obtained pre-treament, pre-consolidation, pre-maintenance, and then every 12 weeks on maintenance.
Pre-treatment, week 5, week 11, and then every 12 weeks until off study

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Samarbejdspartnere

Efterforskere

  • Studiestol: Susan M. Blaney, MD, Baylor College of Medicine

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. august 2005

Primær færdiggørelse (Faktiske)

1. august 2010

Datoer for studieregistrering

Først indsendt

2. juni 2005

Først indsendt, der opfyldte QC-kriterier

2. juni 2005

Først opslået (Skøn)

3. juni 2005

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

30. juni 2011

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

29. juni 2011

Sidst verificeret

1. juni 2011

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Andre undersøgelses-id-numre

  • CDR0000430504
  • U01CA081457 (U.S. NIH-bevilling/kontrakt)
  • PBTC-019

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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