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Ifosfamide With or Without O(6)-Benzylguanine in Treating Patients With Unresectable, Metastatic Solid Tumors

23. januar 2013 opdateret af: National Cancer Institute (NCI)

A Phase I Study Of BG In Combination With Ifosfamide For Advanced Solid Tumors

This randomized phase I trial is studying the side effects and best dose of O(6)-benzylguanine when given together with ifosfamide and to see how well it works compared to ifosfamide alone in treating patients with unresectable metastatic solid tumors. Drugs used in chemotherapy, such as ifosfamide and O(6)-benzylguanine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining ifosfamide with O(6)-benzylguanine may kill more tumor cells

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of O6-benzylguanine when administered with standard high-dose ifosfamide in patients with unresectable, metastatic solid tumors.

II. Determine whether O6-benzylguanine enhances ifosfamide-mediated myelosuppression in patients treated with this regimen.

III. Determine the relationship between O6-benzylguanine dose and intra-individual variability in the degree of myelosuppression in patients treated with this regimen.

IV. Determine the safety and toxicity of this regimen in these patients.

SECONDARY OBJECTIVES:

I. Determine the effect of O6-benzylguanine on pharmacodynamic endpoints, including apoptosis and DNA damage, in patients treated with this regimen.

II. Determine the pharmacokinetics of O6-benzylguanine and its major metabolite, 8-oxoBG, in patients treated with this regimen.

OUTLINE: This is a randomized, open-label, multicenter, dose-escalation study of O6-benzylguanine.

Course 1: All patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.

Course 2: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive high-dose ifosfamide as in course 1.

Arm II: Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3. Cohorts of 6-12 patients receive escalating doses of BG (administered as a bolus and as a continuous infusion during course 2) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity.

Course 3 and all subsequent courses: All patients receive BG (at the MTD determined in course 2, arm II) and high-dose ifosfamide as in course 2, arm II. In all courses, all patients also receive filgrastim (G-CSF) beginning on day 5 and continuing until blood counts recover. In all courses and in both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

32

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

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Histologically confirmed solid tumor

    • Unresectable, metastatic disease
    • No primary tumors
  • Eligible for high-dose ifosfamide-based therapy
  • No known brain metastases
  • Performance status - ECOG 0-1
  • Performance status - Karnofsky 70-100%
  • More than 12 weeks
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Bilirubin normal
  • Creatinine normal
  • Creatinine clearance ≥ 60 mL/min
  • 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 during and for 4 weeks after study participation
  • No history of allergic reaction attributed to compounds of similar chemical or biological composition to O6-benzylguanine or other study agents
  • No concurrent uncontrolled illness
  • No active or ongoing infection
  • No psychiatric illness or social situation that would preclude study compliance
  • More than 24 hours since prior colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF])
  • No prior hematopoietic stem cell transplantation
  • No concurrent pegfilgrastim
  • No concurrent immunotherapy
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • No other concurrent chemotherapy
  • No concurrent hormonal therapy
  • More than 4 weeks since prior radiotherapy and recovered
  • No concurrent therapeutic radiotherapy
  • More than 4 weeks since prior anticancer therapy
  • No more than 2 prior cytotoxic regimens
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer agents or therapies
  • No other concurrent investigational agents

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: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Arm I (ifosfamide)
Patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.
Medicin: ifosfamid
Givet IV
Andre navne:
  • Cyfos
  • Holoxan
  • IFX
  • IFF
  • IPP
Eksperimentel: Arm II (O6-benzylguanine, ifosfamide)
Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3.
Medicin: ifosfamid
Givet IV
Andre navne:
  • Cyfos
  • Holoxan
  • IFX
  • IFF
  • IPP
Medicin: O6-benzylguanin
Givet IV
Andre navne:
  • BG

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in degree of myelosuppression (thrombocytopenia and neutropenia) quantified by both duration of neutropenia and severity of neutropenia
Tidsramme: Baseline up to 1 year
Baseline up to 1 year
Maximum tolerated dose (MTD) of O6-benzylguanine defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity
Tidsramme: 21 days
DLT is defined as any >= grade 3 non-hematologic toxicity, grade 4 thrombocytopenia, or prolonged neutropenia.
21 days

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Pharmacodynamics including apoptosis and DNA damage
Tidsramme: Up to 1 year
Up to 1 year
Pharmacokinetics of O6-benzylguanine
Tidsramme: Up to day 3 of course 2
Summarized using descriptive statistics (mean, median, standard deviation, and interquartile range). Estimated via nonlinear regression.
Up to day 3 of course 2

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: Sonali Smith, 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. juni 2004

Primær færdiggørelse (Faktiske)

1. november 2005

Datoer for studieregistrering

Først indsendt

8. juli 2004

Først indsendt, der opfyldte QC-kriterier

9. juli 2004

Først opslået (Skøn)

12. juli 2004

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

24. januar 2013

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

23. januar 2013

Sidst verificeret

1. januar 2013

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • NCI-2012-02601
  • U01CA069852 (U.S. NIH-bevilling/kontrakt)
  • 12999B
  • CDR0000371909 (Registry Identifier: PDQ (Physician Data Query))

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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