Denna sida har översatts automatiskt och översättningens korrekthet kan inte garanteras. Vänligen se engelsk version för en källtext.

R(+)XK469 in Treating Patients With Advanced Neuroblastoma

13 december 2013 uppdaterad av: 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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

85

Fas

  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Förenta staterna
    • Illinois
      • Chicago, Illinois, Förenta staterna, 60637-1470
        • University of Chicago Comprehensive Cancer Center

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

5 år till 20 år (Barn, Vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Icke-randomiserad
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.
Läkemedel: R(+)XK469
Givet IV
Andra namn:
  • XK469

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Maximum tolerated dose of XK469 in pediatric patients with advanced neuroblastoma
Tidsram: 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
Tidsram: 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
Tidsram: 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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Metabolism of XK469 in pediatric patients
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

National Cancer Institute (NCI)

Utredare

  • Huvudutredare: Susan Cohn, University of Chicago Comprehensive Cancer Center

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 december 2001

Primärt slutförande (Faktisk)

1 september 2009

Studieregistreringsdatum

Först inskickad

4 januari 2002

Först inskickad som uppfyllde QC-kriterierna

26 januari 2003

Första postat (Uppskatta)

27 januari 2003

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

16 december 2013

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

13 december 2013

Senast verifierad

1 december 2013

Mer information

Termer relaterade till denna studie

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • NCI-2009-00013 (Registeridentifierare: CTRP (Clinical Trial Reporting Program))
  • U01CA069852 (U.S.S. NIH-anslag/kontrakt)
  • UCCRC-11108B
  • CDR0000739128
  • NCI-4570
  • 11108B (Annan identifierare: University of Chicago Comprehensive Cancer Center)
  • 4570 (Annan identifierare: CTEP)

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

Kliniska prövningar på Återkommande neuroblastom

Kliniska prövningar på R(+)XK469

Sök liknande försök

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

CROs by country

CROs in Hong Kong

Betingelser

Sällsynta sjukdomar

Läkemedelsinterventioner

Kosttillskott

Sponsor / medarbetare

Platser

3
Prenumerera