- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT02322853
A Multicenter Trial Assessing the Efficacy and Safety of tamOxifen Plus LY2228820 in Advanced or Metastatic Breast Cancer Progressing on aromatasE Inhibitors (OLYMPE)
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).
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Opintotyyppi
Ilmoittautuminen (Todellinen)
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Opiskelupaikat
-
-
-
Bordeaux, Ranska
- Institut Bergonié
-
Caen, Ranska
- Centre François Baclesse
-
Clermont -Ferrand, Ranska
- Centre Jean Perrin
-
Dijon, Ranska
- Centre Georges-Francois Leclerc
-
Lyon, Ranska
- Centre Leon Bérard
-
Marseille, Ranska
- Institut Paoli Calmettes
-
Nantes, Ranska
- Institut de Cancérologie de l'Ouest
-
Paris, Ranska
- Hegp, Ap-Hp
-
Paris, Ranska
- Hôpital St Louis, AP-HP
-
Rennes, Ranska
- Centre Eugène Marquis
-
Rouen, Ranska
- Centre Henri Becquerel
-
St Cloud, Ranska
- Institut Curie
-
Toulouse, Ranska
- Institut Claudius Regaud
-
Villejuif, Ranska
- Institut Gustave Roussy
-
-
Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
---|---|
Active Comparator: TAMOXIFEN
Tamoxifen will be administered daily orally Patients will receive study medication until disease progression or unacceptable toxicity |
hormonotherapy
|
Kokeellinen: 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
Muut nimet:
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Aikaikkuna |
---|---|
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.
Aikaikkuna: at 6 months after treatment start.
|
at 6 months after treatment start.
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
---|---|---|
- To evaluate the toxicity profile (Safety and Tolerability) of the LY2228820 in combination with tamoxifen
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)
|
Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Päätutkija: Christelle LEVY, MD, c.levy@baclesse.unicancer.fr
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Arvio)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Ihosairaudet
- Neoplasmat
- Neoplasmat sivustoittain
- Rintojen sairaudet
- Rintojen kasvaimet
- Huumeiden fysiologiset vaikutukset
- Antineoplastiset aineet
- Hormonit, hormonikorvikkeet ja hormoniantagonistit
- Antineoplastiset aineet, hormonaaliset
- Hormoniantagonistit
- Luutiheyden säilyttämisaineet
- Estrogeeniantagonistit
- Selektiiviset estrogeenireseptorimodulaattorit
- Estrogeenireseptorin modulaattorit
- Tamoksifeeni
Muut tutkimustunnusnumerot
- OLYMPE / 2013-005084-29
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .
Kliiniset tutkimukset Metastaattinen rintasyöpä
-
Gangnam Severance HospitalRekrytointiHER2 Rikastettu alatyyppi Breast Cancer, Herzuma, PAM50 -tutkimusKorean tasavalta
-
Novartis PharmaceuticalsValmisMetastaattinen rintasyöpä (MBC) | Locally Advance Breast Cancer (LABC)Yhdistynyt kuningaskunta, Espanja
-
BioNTech SESeventh Framework ProgrammeValmisRintasyöpä (TNBC (Triple Negative Breast Cancer))Ruotsi, Saksa
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); National Institutes of Health (NIH)Ei vielä rekrytointiaAnatomisen vaiheen II rintasyöpä AJCC v8 | Anatomisen vaiheen III rintasyöpä AJCC v8 | Varhaisen vaiheen rintasyöpä | Anatomic Stage I Breast Cancer American Joint Committee on Cancer (AJCC) v8Yhdysvallat
-
Emory UniversityNational Cancer Institute (NCI)PeruutettuPrognostisen vaiheen IV rintasyöpä AJCC v8 | Metastaattinen pahanlaatuinen kasvain aivoissa | Metastaattinen rintasyöpä | Anatominen vaihe IV Breast Cancer American Joint Committee on Cancer (AJCC) v8
-
Fudan UniversityRekrytointiRintasyöpä | Rintojen kasvain | Rintojen kasvaimet | HER2-positiivinen rintasyöpä | Paikallisesti edennyt rintasyöpä | HER2-negatiivinen rintasyöpä | Hormonireseptoripositiivinen kasvain | Hormonireseptorinegatiivinen kasvain | Varhaisvaiheen rintasyöpä | Triple-negative Breast Cancer (TNBC)Kiina
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)ValmisLymfaödeema | Perioperatiiviset/postoperatiiviset komplikaatiot | Vaiheen II Vulvar Cancer AJCC v7 | Vaihe IIIA Vulvar Cancer AJCC v7 | Vaihe IIIB Vulvar Cancer AJCC v7 | Vaihe IIIC Vulvar Cancer AJCC v7 | Stage IVA Vulvar Cancer AJCC v7 | Vaihe IA Vulvar Cancer AJCC v7 | Vaihe IB Vulvar Cancer AJCC v7 | Vaihe...Yhdysvallat
-
NRG OncologyNational Cancer Institute (NCI)Aktiivinen, ei rekrytointiAnatomisen vaiheen IV rintasyöpä AJCC v8 | Prognostisen vaiheen IV rintasyöpä AJCC v8 | Metastaattinen pahanlaatuinen kasvain luussa | Metastaattinen pahanlaatuinen kasvain imusolmukkeissa | Metastaattinen pahanlaatuinen kasvain maksassa | Metastaattinen rintasyöpä | Metastaattinen pahanlaatuinen kasvain... ja muut ehdotYhdysvallat, Kanada, Saudi-Arabia, Korean tasavalta
-
National Cancer Institute (NCI)NCIC Clinical Trials Group; Cancer and Leukemia Group B; North Central Cancer... ja muut yhteistyökumppanitAktiivinen, ei rekrytointiHormonireseptori positiivinen | Vaiheen IA rintasyöpä AJCC v7 | Vaiheen IB rintasyöpä AJCC v7 | Stage IIA Breast Cancer AJCC v6 ja v7 | Vaiheen IIB rintasyöpä AJCC v6 ja v7 | Vaiheen IIIB rintasyöpä AJCC v7 | Rintojen adenokarsinoomaYhdysvallat, Kanada, Australia, Puerto Rico, Uusi Seelanti, Irlanti, Peru, Yhdistynyt kuningaskunta