- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT00112619
Topotecan in Treating Young Patients With Neoplastic Meningitis Due to Leukemia, Lymphoma, or Solid Tumors
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
Status
Betingelser
Intervention / Behandling
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
Tilmelding (Faktiske)
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
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California
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San Francisco, California, Forenede Stater, 94115
- UCSF Helen Diller Family Comprehensive Cancer Center
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District of Columbia
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Washington, District of Columbia, Forenede Stater, 20010-2970
- Children's National Medical Center
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Illinois
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Chicago, Illinois, Forenede Stater, 60614
- Children's Memorial Hospital - Chicago
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Maryland
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Bethesda, Maryland, Forenede Stater, 20892-1182
- Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02115
- Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
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North Carolina
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Durham, North Carolina, Forenede Stater, 27710
- Duke Comprehensive Cancer Center
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater, 19104-4318
- Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, Forenede Stater, 15213
- Children's Hospital of Pittsburgh
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Tennessee
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Memphis, Tennessee, Forenede Stater, 38105
- St. Jude Children's Research Hospital
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Texas
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Houston, Texas, Forenede Stater, 77030
- Dan L. Duncan Cancer Center at Baylor College of Medicine
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Washington
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Seattle, Washington, Forenede Stater, 98105
- Children's Hospital and Regional Medical Center - Seattle
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
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
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
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Number of patients with dose-limiting toxicity
Tidsramme: First 14 days of therapy
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First 14 days of therapy
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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.
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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.
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Day 1 of Week 1
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Correlation of imaging parameters with tumor response
Tidsramme: Pre-treatment, week 5, week 11, and then every 12 weeks until off study
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MRI scans of the brain and spine is obtained pre-treament, pre-consolidation, pre-maintenance, and then every 12 weeks on maintenance.
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Pre-treatment, week 5, week 11, and then every 12 weeks until off study
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Studiestol: Susan M. Blaney, MD, Baylor College of Medicine
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
- uspecificeret barndom solid tumor, protokol specifik
- højgradigt cerebralt astrocytom i barndommen
- stadium IV barndom små non-cleaved cell lymfom
- stadium IV storcellet lymfom i barndommen
- tilbagevendende små ikke-spaltede celle lymfomer i barndommen
- tilbagevendende storcellet lymfom i barndommen
- juvenil myelomonocytisk leukæmi
- kronisk myelogen leukæmi i barndommen
- AIDS-relateret perifert/systemisk lymfom
- AIDS-relateret diffust storcellet lymfom
- AIDS-relateret immunoblastisk storcellet lymfom
- AIDS-relateret små ikke-spaltet celle lymfom
- AIDS-relateret diffust blandet celle lymfom
- AIDS-relateret diffust små spaltet celle lymfom
- tilbagevendende/refraktær Hodgkin-lymfom i barndommen
- recidiverende kronisk myelogen leukæmi
- AIDS-relateret lymfoblastisk lymfom
- primært non-Hodgkin lymfom i centralnervesystemet
- tilbagevendende akut lymfatisk leukæmi hos børn
- stadium IV barndoms lymfoblastisk lymfom
- barndom infratentorial ependymom
- atypisk teratoid/rhabdoid tumor i barndommen
- stadium IV barndom Hodgkin lymfom
- tilbagevendende akut myeloid leukæmi i barndommen
- tilbagevendende lymfoblastisk lymfom i barndommen
- tilbagevendende karcinom af ukendt primær
- tilbagevendende barndomsgrad III lymfomatoid granulomatose
- barndom supratentorial ependymom
- barndoms oligodendrogliom
- tilbagevendende supratentorial primitiv neuroektodermal tumor i barndommen
- tilbagevendende cerebellar astrocytom i barndommen
- tilbagevendende cerebralt astrocytom i barndommen
- tilbagevendende barndoms ependymom
- tilbagevendende medulloblastom i barndommen
- tilbagevendende barndomssynsvej og hypothalamus gliom
- barndoms kraniopharyngiom
- barndommens kimcelletumor i centralnervesystemet
- barndom choroideus plexus tumor
- meningeom i barndomsklasse I
- meningiom i barndommens grad II
- meningiom i barndommens grad III
- AIDS-relateret primært CNS-lymfom
- HIV-associeret Hodgkin lymfom
- primært centralnervesystem Hodgkin lymfom
- barndom lavgradigt cerebralt astrocytom
- leptomeningeale metastaser
- sekundært centralnervesystem Hodgkin lymfom
- tilbagevendende pineoblastom i barndommen
- tilbagevendende barndoms subependymale kæmpecelleastrocytom
- meningeal leukemia
- secondary central nervous system non-Hodgkin lymphoma
Yderligere relevante MeSH-vilkår
- Sygdomme i centralnervesystemet
- Sygdomme i nervesystemet
- Sygdomme i immunsystemet
- Neoplasmer efter histologisk type
- Lymfoproliferative lidelser
- Lymfesygdomme
- Immunproliferative lidelser
- Neoplasmer efter sted
- Meningeale neoplasmer
- Neoplasmer
- Lymfom
- Leukæmi
- Neoplasmer i nervesystemet
- Neoplasmer i centralnervesystemet
- Meningitis
- Meningeal karcinomatose
- Molekylære mekanismer for farmakologisk virkning
- Enzymhæmmere
- Antineoplastiske midler
- Topoisomerasehæmmere
- Topoisomerase I-hæmmere
- Topotecan
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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