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Tipifarnib in Treating Patients With Myelodysplastic Syndromes

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

Phase I Study of the Farnesyl Transferase Inhibitor R115777 (NSC #702818) in Patients With Myelodysplastic Syndrome

This phase I trial studies the side effects and best dose of tipifarnib in treating patients with myelodysplastic syndromes. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

PRIMARY OBJECTIVES:

I. To determine the toxicity profile and antitumor activity of the farnesyltransferase (FTase) inhibitor R115777 (tipifarnib) in patients with myelodysplastic syndrome (MDS) treated on a one week on/one week off schedule.

II. To determine the effect on R115777 on a one week on/one week off schedule on FTase activity, prenylation of RAS and other substrates and on downstream effects.

OUTLINE: This is a dose-escalation study.

Patients receive tipifarnib orally (PO) twice daily (BID) on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

65

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
    • Texas
      • Houston, Texas, Forenede Stater, 77030
        • M D Anderson 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:

  • Patients must have histologically MDS (including French-American-British [FAB] types refractory anemia [RA], refractory anemia with ringed sideroblasts [RARS], refractory anemia with excess blasts [RAEB], refractory anemia with excess blasts in transformation [RAEBT], or chronic myelomonocytic leukemia [CMMoL]); for the purpose of the study, all patients will be classified by World Health Organization (WHO) criteria

    • By these criteria, FAB RA are split into:

    • Pure dyserythropoietic refractory anemia (PRA)

      • Refractory cytopenia with multilineage dysplasia (RCMD)

    • FAB RARS is split into:

      • Pure sideroblastic anemia (PSA)
      • Refractory sideroblastic cytopenia with multilineage dysplasia (RSCMD)

    • FAB RAEB is split into:

      • RAEB I (< 10% BM blasts)
      • RAEB II (10-20% BM blasts)
    • Patients with CMMoL, and RAEBT by FAB classification will be included in the protocol
  • Prognosis will be assessed by International Prognostic Scoring System (IPSS) criteria
  • =< 2 prior therapies
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy of greater than 12 weeks
  • Bilirubin =< 1.5mg %
  • Creatinine =< 1.5mg %
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 4 weeks (3 months for UCN01) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to R115777 (such as imidazoles)
  • Patients eligible for bone marrow transplant (=< 60 years old), with a compatible sibling, no contraindications for transplant
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with R115777.
  • Growth factors other than filgrastim (G-CSF) are excluded; patients should be off excluded growth factors for 2 weeks

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 (tipifarnib)
Patients receive tipifarnib PO BID on weeks 1, 3, 5, and 7. Treatment repeats every 8 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Andet: laboratoriebiomarkøranalyse
Korrelative undersøgelser
Andet: farmakologisk undersøgelse
Korrelative undersøgelser
Andre navne:
  • farmakologiske undersøgelser
Medicin: tipifarnib
Givet PO
Andre navne:
  • R115777
  • Zarnestra

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
MTD defined as the next lower dose level at which 2 patients experience dose limiting toxicity (DLT) defined as grade 3 or 4 toxicity according to the Cancer Therapy Evaluation Program Common Toxicity Criteria
Tidsramme: Up to 8.5 years
The final analysis will report all toxicities by grade, dose, cycle, and by cumulative dose.
Up to 8.5 years
Response rate
Tidsramme: Up to 8.5 years
Will be reported overall and by dose level.
Up to 8.5 years

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
FTase inhibition
Tidsramme: Up to 8.5 years
Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).
Up to 8.5 years
Accumulation of unfarnesylated lamin B1
Tidsramme: Up to 8.5 years
Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).
Up to 8.5 years
Accumulation of RAS proteins
Tidsramme: Up to 8.5 years
Based on the shape of the relationship (e.g. linear vs saturation vs peak), a dose response analysis will be performed to describe/summarize the relationship (correlation analysis or curve-fitting).
Up to 8.5 years

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: Razelle Kurzrock, M.D. Anderson 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 2002

Primær færdiggørelse (Faktiske)

1. september 2009

Datoer for studieregistrering

Først indsendt

2. juni 2000

Først indsendt, der opfyldte QC-kriterier

28. august 2003

Først opslået (Skøn)

29. august 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-2009-01158 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U01CA062461 (U.S. NIH-bevilling/kontrakt)
  • 5625 (Anden identifikator: CTEP)
  • CDR0000067862
  • DM01-582 (Anden identifikator: M D Anderson Cancer Center)

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 Kronisk myelomonocytisk leukæmi

Kliniske forsøg med laboratoriebiomarkøranalyse

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Betingelser

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Placeringer

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