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Vorinostat and Alvocidib in Treating Patients With Advanced Solid Tumors

21. februar 2014 opdateret af: National Cancer Institute (NCI)

A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Flavopiridol in Advanced Solid Tumors

This phase I trial is studying the side effects and best dose of vorinostat when given together with alvocidib in treating patients with advanced solid tumors. Drugs used in chemotherapy, such as vorinostat and alvocidib, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat together with alvocidib may kill more tumor cells.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

OBJECTIVES:

I. Determine the maximum tolerated dose of vorinostat (SAHA) when given in combination with flavopiridol (alvocidib) in patients with advanced solid tumors.

II. Obtain preliminary data on the therapeutic activity of SAHA and flavopiridol in these patients.

III. Evaluate the role of p21, p53, and apoptotic markers relative to treatment response in patients treated with this regimen.

OUTLINE: This is a multicenter, open label, non-randomized, dose-escalation study of vorinostat (SAHA).

Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug. Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib intravenously (IV) over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of SAHA until the 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. An additional 10 patients are treated at the MTD of SAHA in combination with fixed-dose alvocidib. Once the MTD of SAHA in combination with fixed-dose alvocidib is determined, patients receive oral SAHA at one dose level below the MTD once daily on days 1-3 and 8-10 and divided-dose alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. If this schedule is well-tolerated, the MTD of SAHA in combination with divided-dose flavopiridol is determined as above. An additional 10 patients are treated at the MTD of SAHA in combination with divided-dose alvocidib. Patients undergo blood draws on days 1 and 9 of course 1 for pharmacokinetic analysis.

After completion of study treatment, patients are followed for 4 weeks.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

60

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
    • New York
      • New York, New York, Forenede Stater, 10065
        • Memorial Sloan-Kettering 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

    • Metastatic or unresectable disease
    • Standard curative or palliative measures do not exist or are no longer effective
  • No hematologic malignancies
  • No known brain metastases
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin ≤ 1.5 mg/dL
  • AST and ALT ≤ 2.5 times upper limit of normal
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs

  • No uncontrolled intercurrent illness, including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situations that would preclude study compliance
  • Recovered from prior therapy
  • At least 2 weeks since prior histone acetylase inhibitors, including valproic acid
  • At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • At least 2 weeks since prior investigational therapy
  • At least 2 weeks since prior radiotherapy
  • No concurrent combination antiretroviral therapy for HIV-positive patients

  • No concurrent commonly used vitamins, antioxidants, or herbal preparations and supplements

    • A single tablet multivitamin is allowed
  • No other concurrent anticancer agents or therapies for this mailgnancy
  • 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: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Treatment (chemotherapy, enzyme inhibitor)
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug. Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib IV over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Medicin: alvocidib
Givet IV
Andre navne:
  • FLAVO
  • flavopiridol
  • HMR 1275
  • L-868275
Andet: farmakologisk undersøgelse
Korrelative undersøgelser
Andre navne:
  • farmakologiske undersøgelser
Medicin: vorinostat
Gives oralt
Andre navne:
  • SAHA
  • Zolinza
  • L-001079038
  • suberoylanilid hydroxamsyre

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Maximum tolerated dose of vorinostat when administered in combination with a fixed dose of weekly flavopiridol
Tidsramme: Course 1
Defined as the dose one level below the dose at which two or more of the patients in the initial cohort experience dose limiting toxicities (DLT) during the first treatment course. Graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 Term.
Course 1

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Clinical pharmacokinetics of vorinostat (SAHA)
Tidsramme: Week 1 of course 1
Week 1 of course 1
Therapeutic activity of SAHA and flavopiridol
Tidsramme: Not Provided
Not Provided
Expression of p21, p53, and apoptotic markers relative to treatment response
Tidsramme: Baseline to 2 weeks after completion of study treatment
Evaluated using immunohistochemistry.
Baseline to 2 weeks after completion of study treatment

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: Gary Schwartz, Memorial Sloan Kettering 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. marts 2006

Primær færdiggørelse (Faktiske)

1. april 2009

Datoer for studieregistrering

Først indsendt

10. maj 2006

Først indsendt, der opfyldte QC-kriterier

10. maj 2006

Først opslået (Skøn)

11. maj 2006

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

24. februar 2014

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

21. februar 2014

Sidst verificeret

1. oktober 2011

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • NCI-2009-00090 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U01CA069856 (U.S. NIH-bevilling/kontrakt)
  • P30CA008748 (U.S. NIH-bevilling/kontrakt)
  • 6858 (CTEP)
  • 05-109 (Anden identifikator: Memorial Sloan-Kettering Cancer Center)
  • MSKCC-05109
  • CDR0000472411
  • NCI-6858

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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