Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

R(+)XK469 in Treating Patients With Advanced Neuroblastoma

13. december 2013 opdateret af: National Cancer Institute (NCI)

Phase I Study Of R(+)XK469 In Patients With Advanced Neuroblastoma

This phase I trial is studying the side effects and best dose of R(+)XK469 in treating patients with advanced neuroblastoma. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

OBJECTIVES:

I. Determine the maximum tolerated dose, recommended phase II dose, and dose-limiting toxicity of R(+)XK469 in two different dosing schedules in patients with advanced neuroblastoma.

II. Determine the safety of this drug in these patients. III. Determine the tolerance to this drug in these patients. IV. Determine the pharmacokinetics and pharmacodynamics of this drug and its metabolites in these patients.

V. Determine, preliminarily, any antineoplastic activity of this drug in these patients.

OUTLINE: This is a dose-escalation study.

SCHEDULE A: Patients receive R(+)XK469 intravenously (IV) over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).

SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

85

Fase

  • Fase 1

Kontakter og lokationer

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

Studiesteder

  • Forenede Stater
    • Illinois
      • Chicago, Illinois, Forenede Stater, 60637-1470
        • University of Chicago Comprehensive Cancer Center

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

5 år til 20 år (Barn, Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Histologically confirmed high-risk neuroblastoma that has relapsed or is refractory to standard therapy

  • No active brain metastases

    • Previously treated brain metastases allowed if there is no requirement for corticosteroids or anticonvulsants
  • Performance status - Karnofsky performance status 70-100% or Lansky score ≥ 70 for your pediatric patients
  • More than 3 months
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin normal (unless due to documented Gilbert's syndrome)
  • Creatinine less than 1.5 times upper limit of normal
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other concurrent uncontrolled illness that would preclude study participation
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study participation
  • No prior allergic reaction to compounds of similar chemical or biological composition to study drug (e.g., flurbiprofen or ibuprofen)
  • No HIV-positive patients
  • No concurrent biologic agents
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • No other concurrent chemotherapy
  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy
  • No concurrent palliative radiotherapy
  • See Disease Characteristics
  • Recovered from all prior therapy
  • No other concurrent investigational agents
  • No concurrent commercial agents or therapies directed at malignancy
  • No concurrent combination anti-retroviral therapy for HIV-positive patients

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: Ikke-randomiseret
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Treatment (chemotherapy)

SCHEDULE A: Patients receive R(+)XK469 IV over 30 minutes on days 1, 3, and 5. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of R(+)XK469 until the recommended phase II dose or MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued and treated at the recommended phase II dose (for a maximum of 20 patients treated at that dose).

SCHEDULE B: Once the recommended phase II dose is determined on schedule A, additional patients are accrued and receive escalating doses of R(+)XK469 IV over 30-60 minutes on day 1, beginning at a reduced dose. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Dose escalation continues as in Schedule A.
Medicin: R(+)XK469
Givet IV
Andre navne:
  • XK469

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Maximum tolerated dose of XK469 in pediatric patients with advanced neuroblastoma
Tidsramme: Day 29 of course 1
Defined as the highest dose studied for which the incidence of dose-limiting toxicity (DLT) was less than 33%.
Day 29 of course 1
DLT
Tidsramme: Day 29 of course 1
Defined as the occurrence of any of the following: 1) grade 3 or higher nonhematologic toxicity except fatigue, alopecia, nausea, vomiting, 2) grade 4 thrombocytopenia or anemia, 3) any fever accompanied by granulocyte count < 1000/mm^3 (grade 3 or 4 neutropenia), 4) failure to recover absolute neutrophil count 1500/μL
Day 29 of course 1
Recommended phase II dose
Tidsramme: Day 29 of course 1
Generally defined as the MTD. For both schedules A and B and the pediatric dosing schedule, once the recommended phase II dose has been tentatively defined, a total of 12 evaluable patients will be studied to ensure the feasibility of this dose for phase II trials. If interindividual pharmacokinetic variability is high, additional patients will be enrolled (maximum of 20 at the phase II dose) to permit adequate pharmacological characterization of XK469 and the relationship of interindividual pharmacokinetic variability to toxicity.
Day 29 of course 1

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Metabolism of XK469 in pediatric patients
Tidsramme: Days 1-3 of course 1
Performed by high-performance liquid chromatography (HPLC). Plasma metabolic ratios between metabolite and XK469 concentrations will be used as an index of metabolic activity and phenotype for each patient. The modality of the frequency distribution of metabolic ratios will be also described.
Days 1-3 of course 1
Pharmacokinetics of XK469 in pediatric patients
Tidsramme: Days 1-3 of course 1
The maximum number of samples for pharmacokinetic studies will not exceed 20. Analyzed by non compartmental method using the WinNonlin software. Parameters include the elimination rate constant, the area under the concentration vs. time curve (AUC), terminal half-life, total (nonrenal + renal) clearance, and volume of distribution at steady state. Mean, standard deviation, and coefficient of variation will be determined for each parameter.
Days 1-3 of course 1
Pharmacodynamics of XK469 in pediatric patients
Tidsramme: Continuously over the course of study treatment
Performed by correlating area under the curve (AUC) (and other parameters) of R(+)XK469 and metabolites with observed toxicities. Specifically, we will compare the AUC in those patients who experience grade >= 2 toxicity to those who experience grade < 2 toxicity using a Wilcoxon, nonparametric rank-sum test.
Continuously over the course of study treatment
Antineoplastic activity of XK469 for neuroblastoma
Tidsramme: Every 2 courses
Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
Every 2 courses

Samarbejdspartnere og efterforskere

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

Sponsor

National Cancer Institute (NCI)

Efterforskere

  • Ledende efterforsker: Susan Cohn, University of Chicago Comprehensive Cancer Center

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. december 2001

Primær færdiggørelse (Faktiske)

1. september 2009

Datoer for studieregistrering

Først indsendt

4. januar 2002

Først indsendt, der opfyldte QC-kriterier

26. januar 2003

Først opslået (Skøn)

27. januar 2003

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

16. december 2013

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

13. december 2013

Sidst verificeret

1. december 2013

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • NCI-2009-00013 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U01CA069852 (U.S. NIH-bevilling/kontrakt)
  • UCCRC-11108B
  • CDR0000739128
  • NCI-4570
  • 11108B (Anden identifikator: University of Chicago Comprehensive Cancer Center)
  • 4570 (Anden identifikator: CTEP)

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 .

Kliniske forsøg med Tilbagevendende neuroblastom

Kliniske forsøg med R(+)XK469

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Mauritius

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

3
Abonner