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A Multicenter Trial Assessing the Efficacy and Safety of tamOxifen Plus LY2228820 in Advanced or Metastatic Breast Cancer Progressing on aromatasE Inhibitors (OLYMPE)

23 maggio 2017 aggiornato da: Centre Francois Baclesse

A Randomized Open-label Phase II Multicenter Trial Assessing the Efficacy and Safety of tamOxifen Plus LY2228820 in Advanced or Metastatic Breast Cancer Progressing on aromatasE Inhibitors

Metastatic breast cancer (MBC) remains an incurable disease and despite an improvement of the effect of systemic treatments. After relapse on first-line non-steroidal aromatase inhibitor, current clinical practice and treatment guidelines include tamoxifen, fulvestrant (an ER antagonist) and exemestane as available options (NCCN treatment guidelines 2012), but in this context of resistance, their efficacy are poor.

Some results confirm the possibility to improve the efficacy of tamoxifen in metastatic setting by a combination with therapy targeting signal transduction pathways. Other transduction pathways seem to be involved in endocrine sensitivity/resistance, such as RAS/RAF/MEK/MAK pathway.

LY2228820 inhibits the activity of p38 MAPK (selective inhibitor of the α and β isoforms of p38 MAPK in vitro) and reduces phosphorylation of its cellular target, MAPK-activated protein kinase 2 (MAPKAP-K2).

Panoramica dello studio

Tipo di studio

Interventistico

Iscrizione (Effettivo)

8

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

      • Bordeaux, Francia
        • Institut Bergonié
      • Caen, Francia
        • Centre Francois Baclesse
      • Clermont -Ferrand, Francia
        • Centre Jean Perrin
      • Dijon, Francia
        • Centre Georges-François Leclerc
      • Lyon, Francia
        • Centre Leon Berard
      • Marseille, Francia
        • Institut Paoli Calmettes
      • Nantes, Francia
        • Institut de Cancerologie de L'Ouest
      • Paris, Francia
        • Hegp, Ap-Hp
      • Paris, Francia
        • Hôpital St Louis, AP-HP
      • Rennes, Francia
        • Centre Eugène Marquis
      • Rouen, Francia
        • Centre Henri Becquerel
      • St Cloud, Francia
        • Institut Curie
      • Toulouse, Francia
        • Institut Claudius Regaud
      • Villejuif, Francia
        • Institut Gustave Roussy

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Femmina

Descrizione

Inclusion Criteria:

  • Women with histologically confirmed breast cancer
  • 18 < age < 80 years old
  • Menopausal status Women are considered post-menopausal and not of child bearing potential if they have had

    • 12 months of spontaneous amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or
    • 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or
    • surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
  • ER-positive status by local laboratory testing (>10% by IHC) and HER2-negative status (IHC 0 or 1+ or 2+ and FISH negative) on the last biopsy or surgical specimen available.
  • Disease progression defined as inoperable locally advanced or metastatic breast cancer (MBC) excluding aggressive visceral disease requiring other approaches, such as chemotherapy
  • Disease refractory to aromatase inhibitors (AI) defined as:

    • recurrence while on, or within 12 months of end of adjuvant treatment with aromatase inhibitor, or
    • progression while on, or within 3 months of end of AI for locally advanced or MBC
  • Patients who have received fulvestrant are eligible
  • Maximum 2 previous lines of chemotherapy for MBC
  • Performance Status (PS) ≤ 2
  • Patient able to swallow and retain oral medication
  • Measurable or evaluable lesions as per RECIST 1.1

    • Measurable disease (≥ 20 mm by conventional techniques or ≥ 10 mm by spiral computed tomography scan) or
    • Non-measurable lytic or mixed (lytic + blastic) bone lesions in the absence of measurable disease.
    • Patients with only pleural effusion and/or ascites are not eligible.
  • Adequate bone marrow and organ function as defined by the following laboratory values:

    • Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
    • Platelets (plt) ≥ 100 x 109/L
    • Hemoglobin (Hgb) ≥ 9 g/dl
    • INR ≤ 1.5 without any anticoagulation treatment
    • Serum creatinine ≤ 1.5 x ULN
    • Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) within normal range (or < 3.0 x ULN if liver metastases are present)
    • Total serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's Syndrome, which is defined as presence of several episodes of unconjugated hyperbilirubinemia with normal results from CBC count (including normal reticulocyte count and blood smear), normal liver function test results, and absence of other contributing disease processes at the time of diagnosis
  • Patient has signed informed consents obtained before any trial related activities and according to local guidelines

Exclusion Criteria:

  • • Previous treatment with p38 MAPK inhibitors or Tamoxifen in metastatic setting (adjuvant treatment by tamoxifen is allowed)

    • More than 2 lines of chemotherapy for locally advanced and/or metastatic breast cancer
    • Brain metastasis
    • Other malignancy (with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer).
    • Clinically significant (i.e. active) cardiovascular disease: cerebro-vascular accident/stroke or myocardial infarction within 6 months prior to first study medication; unstable angina; CHF of New York Heart Association (NYHA) Grade II or higher; or serious cardiac arrhythmia requiring medication.
    • Have had a major bowel resection that would alter oral drug absorption.
    • Have a diagnosis of inflammatory bowel disease (Crohn's disease or ulcerative colitis).
    • Are receiving concurrent administration of immunosuppressive therapy
    • Concurrent participation in any therapeutic clinical trial
    • Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: TAMOXIFEN

Tamoxifen will be administered daily orally

Patients will receive study medication until disease progression or unacceptable toxicity

hormonotherapy
Sperimentale: TAMOXIFEN + LY2228820

Tamoxifen will be administered daily orally LY2228820 dimesylate (Ralimetinib) will be administered orally

Patients will receive study medication until disease progression or unacceptable toxicity

hormonotherapy
Altri nomi:
  • terapia mirata

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
To define the efficacy (progression-free survival rate at 6 months) of LY2228820 in combination with tamoxifen for postmenopausal women with an ER positive and HER2 negative advanced or metastatic breast cancer who progressed on aromatase inhibitors.
Lasso di tempo: at 6 months after treatment start.
at 6 months after treatment start.

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
- To evaluate the toxicity profile (Safety and Tolerability) of the LY2228820 in combination with tamoxifen
Lasso di tempo: From date of randomization until study participation (during average 12 months)
Adverse events description and grade in all participants
From date of randomization until study participation (during average 12 months)
- To estimate the Progression-Free Survival of the LY2228820 in combination with tamoxifen
Lasso di tempo: evaluated every 8-12 weeks (during average 12 months)
evaluated every 8-12 weeks (during average 12 months)
- To assess the overall survival of the LY2228820 in combination with tamoxifen
Lasso di tempo: From date of randomization until the date of first documented date of death from any cause, whichever came first, assessed up to 60 months
From date of randomization until the date of first documented date of death from any cause, whichever came first, assessed up to 60 months
- To assess response duration of the LY2228820 in combination with tamoxifen
Lasso di tempo: evaluated every 8-12 weeks during treatment to progression or death for any cause.(during average 12 months)
evaluated every 8-12 weeks during treatment to progression or death for any cause.(during average 12 months)

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Investigatori

  • Investigatore principale: Christelle LEVY, MD, c.levy@baclesse.unicancer.fr

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

1 gennaio 2015

Completamento primario (Effettivo)

1 aprile 2017

Completamento dello studio (Effettivo)

1 aprile 2017

Date di iscrizione allo studio

Primo inviato

12 dicembre 2014

Primo inviato che soddisfa i criteri di controllo qualità

22 dicembre 2014

Primo Inserito (Stima)

23 dicembre 2014

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

24 maggio 2017

Ultimo aggiornamento inviato che soddisfa i criteri QC

23 maggio 2017

Ultimo verificato

1 maggio 2017

Maggiori informazioni

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su Cancro al seno metastatico

Prove cliniche su Tamoxifen

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