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

Phase II Dasatinib Study in Advanced Breast Cancer

15. juli 2013 opdateret af: Duke University

A Phase II Trial of Dasatinib to Treat Women With Stage IV or Inoperable Stage III Advanced Breast Cancer

The purpose of this study is to find out if dasatinib will safely reduce the size or spread of your tumor.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

The introduction of biologics with specific molecular targets has initiated a trend toward improved survival in women with metastatic breast cancer.

The tyrosine kinase SRC (pp60src) is a member of a family of proteins that contribute to cellular signal transduction activities such as cell growth, differentiation, survival, adhesion and migration. Abnormal signaling has been linked to cancer metastases; thus, identification of molecular regulators or inhibitors of SRC present therapeutic opportunity for cancer patients. Src kinases consist of eight non-receptor tyrosine kinases (Src, Fyn, Yes, Lck, Lyn, Hck, Fgr and Blk) that interact with the intracellular domains of growth factor/cytokine receptors, (G-protein-coupled receptor)GPCRs and integrins.

Inhibition of SRC has also been associated with reversal of chemoresistance and restored sensitivity to drug-resistant ovarian cancer cells, suggesting potential as second- line treatment for previously treated populations. Dasatinib is a potent, broad spectrum inhibitor of 5 critical oncogenic tyrosine kinases, including SRC.

Patients will receive dasatinib, a Src inhibitor, at an initial dose of 50 mg PO BID, with real-time PharmacoDynamic dose adjustment following 4 weeks of therapy based on inhibition of phosphorylation of SRC, focal adhesion kinase (FAK) and paxillin, until progression. The primary objective is to assess tolerability and estimate the proportion of patients who are progression-free at 16 weeks from the date of study enrollment.

A minimum of 2 (maximum of 3) tumor biopsies will be analyzed and compared for SRC signature: one at baseline (study enrollment, all patients); the second after 4 weeks of dasatinib therapy (all patients); and the third at progression (only patients who progress after a documented response).

Patients will receive continuous daily administration until documented disease progression, and will be followed until death.

The results of this study may be useful in designing future studies using dasatinib alone or in combination with chemotherapy, thus having the potential to alter the current standard of care in this incurable population.

Additional correlative studies will be conducted. Tumor biopsies will be analyzed and compared for SRC, pSRC, Ki67, and related genomic signatures.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

31

Fase

  • Fase 2

Kontakter og lokationer

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

Studiesteder

  • Forenede Stater
    • Florida
      • West Palm Beach, Florida, Forenede Stater, 33401
        • Palm Beach Cancer Center Institute
    • North Carolina
      • Charlotte, North Carolina, Forenede Stater, 28204
        • Presbyterian Health Care
      • Durham, North Carolina, Forenede Stater, 27710
        • Duke University Medical 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

Kvinde

Beskrivelse

Inclusion Criteria:

  • Measurable Stage IV or inoperable Stage III advanced breast cancer.
  • There is no limit on the number of prior therapies.
  • At least 3 weeks since prior chemotherapy, biological or hormonal therapy.
  • At least 2 weeks since surgical biopsy.
  • At least 3 weeks since major (open thoracic/abdominal/cardiac) surgery.
  • No central nervous system (CNS) metastases except solitary brain metastasis
  • No cardiac dysfunction
  • left ventricular ejection fraction (LVEF) ≥ 50% as determined by multiple gated acquisition scan (MUGA)/echocardiogram
  • Adequate blood counts
  • Normal liver and kidney function
  • Negative serum pregnancy test.
  • Able to provide informed consent

Exclusion Criteria:

  • Pregnant or breast feeding.
  • Prior treatment with dasatinib.
  • Bone as the only site of disease.
  • Significant gastrointestinal bleeding
  • Septicemia, infection, acute hepatitis, hypokalemia, or hypomagnesemia

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: Dasatinib
50- 100 mg PO BID
Medicin: Dasatinib
An initial dose of 50 mg PO BID; following 4 weeks of treatment, dose adjustment will be based on inhibition of phosphorylation of FAK and paxillin per biopsy assessment, as well as toxicity assessment.
Andre navne:
  • BMS-354825
  • Sprycel

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Estimation of the Proportion of Progression-free Patients at 16 Wks.
Tidsramme: 16 weeks

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or measurable increase in a non-target lesion, or the appearance of new lesions, or similar definition as appropriate.

Proportion progression-free at 16 weeks.From first day of study related treatment with Dasatinib until the date of first documented progression or date of death from any cause, whichever came first.
16 weeks

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
To Measure Response to Protocol Therapy Per RECIST Criteria
Tidsramme: 16 weeks

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression At least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as a reference the smallest sum longest diameter recorded since treatment started, or the appearance of one or more new lesions.

RECIST 1.0 Overall response:

Complete Response (CR) Partial Response (PR) Stable Disease (SD) Progressive Disease (PD)

CR= CR+CR and No new lesions PR= CR+SD; PR+SD and no new lesions SD= SD+SD and no new lesions PD= PD+any new lesions
16 weeks
Characterization and Comparison of SRC (A Protein Tyrosine Kinase)Dysregulation at Baseline (All Patients), After 4 Weeks of Dasatinib Treatment (All Patients), and at Progression (Only Patients Who Progress After Documented Response)
Tidsramme: 4 weeks
For the 20 patients with evaluable biopsies at baseline and week 4, the median relative change from baseline in tissue biomarker levels of phospho-Src (p-Src)
4 weeks
Correlate SRC Dysregulation Results With Response to Dasatinib Therapy
Tidsramme: 16 weeks
Since all patients progressed there is no comparison to between responders and non-responders.
16 weeks
To Explore the Association Between Each Patient's SRC Signature and Their Time to Progression.
Tidsramme: Baseline Src measure to first progression
Spearman's correlation between the change in SRC signature from baseline to 4 weeks and time to progression
Baseline Src measure to first progression
To Explore the Association Between Dasatinib and Osteoclastic Bone Resorption
Tidsramme: not assessed
Not assessed secondary to limited number of subjects.
not assessed

Samarbejdspartnere og efterforskere

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

Sponsor

Duke University

Samarbejdspartnere

Bristol-Myers Squibb

Efterforskere

  • Ledende efterforsker: Kimberly Blackwell, MD, Duke University

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. oktober 2007

Primær færdiggørelse (Faktiske)

1. maj 2011

Studieafslutning (Faktiske)

1. maj 2011

Datoer for studieregistrering

Først indsendt

16. oktober 2007

Først indsendt, der opfyldte QC-kriterier

16. oktober 2007

Først opslået (Skøn)

18. oktober 2007

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

17. juli 2013

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

15. juli 2013

Sidst verificeret

1. juli 2013

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • Pro00007578
  • BMS CA180089

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 Avanceret brystkræft

Kliniske forsøg med Dasatinib

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Costa Rica

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner