Etude : UTOLA / GINECO-EN-104b

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Acronyme / Nom
Situation thérapeutique
Cadre réglementaire
Présentation de l'étude
Acronyme / Nom : UTOLA / GINECO-EN-104b

Situation thérapeutique : Métastatique ou localement avancé

Traitement : Thérapie ciblée

Cadre réglementaire : RIPH2

Dernière MÀJ : 07/10/2021
CIM10 - Localisation(s)
Informations principales
Titre : Etude de phase II randomisée en double aveugle contre placebo, multicentrique évaluant l’Olaparib comme traitement de maintenance chez des patientes sensibles au platine pour un carcinome de l’endomètre avancé ou métastatique

Spécialité : Seins, organes génitaux de la femme
Localisation : C54 - Tumeur maligne du corps de l'utérus
Informations complémentaires
Schéma : This is a phase IIB, national, randomized, double-blinded, comparative, multi-center study, to assess the efficacy of Olaparib as maintenance after a platinum based chemotherapy in patients with Advanced or metastatic endometrial cancer.

Approximately 147 patients will be randomized using an Interactive Voice Response System / Interactive web system (IVR/IWR system) in a 2:1 ratio to the treatments as specified below :
- Olaparib tablets per os 300 mg twice daily,
- Placebo tablets per os 300 mg twice daily.

Before randomization to the study :
- Patient should be without evidence of disease (NED), or in clinical complete response or in partial response or stable.
- Patient must have completed a minimum of 4 cycles of first line platinum based chemotherapy (recommended chemotherapy is carboplatine AUC 5 plus paclitaxel 175 mg/m2).

Patient will be stratified according to :
- P53 and MMR Immunohistochemistry, (Y/N)
- Response to previous chemotherapy line (Objective response versus Stable)

Patients will receive Olaparib/Placebo up to disease progression.

Phase : II

Stade : Localement avancé à Métastatique

Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Female Patient ≥18 years at the day of consenting to the study
- Provision of informed consent prior to any study specific procedures
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status < 2
- Patient with advanced/metastatic endometrial cancer not candidate to a curative treatment with surgery or radiotherapy
- Patients who have completed prior to randomization one Platine based chemotherapy for advanced disease after 6 cycles of chemotherapy (at least 4 cycles of platine). Patients must have a measurable disease according RECIST 1-1 at the initiation of the chemotherapy (cf. appendix 3)
- Patients must be prior to randomization without evidence of disease (NED) or in complete response (CR) or partial response (PR) or stable disease from the chemotherapy
- Patient should have been tested biolology for IHC : P53 and MMR within two weeks before the randomisation and (NGS; BRCA/HRD) within 3 months after the randomisation
- Patients could have been previously treated with Hormone-therapy
- Adjuvant chemotherapy or local radio-chemotherapy is allowed (with a delay of at least of 12 months). First recurrence at least 12 months after a loco-regional treatment.
- Patients pay have received external beam +/- vaginal brachytherapy
- All histologic and molecular subtypes of endometrial carcinoma will be included (including mixte histology), except carcinosarcoma, neuro-endocrine and small cells carcinoma.
- Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
--> Haemoglobin ≥10.0 g/dL with no blood transfusion in the past 28 days
--> Absolute neutrophil count (ANC) ≥1.5 x 109/L
--> Platelet count ≥100 x 109/L
--> Total bilirubin ≤1.5 x institutional upper limit of normal (ULN)
--> Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤5x ULN
--> Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of ≥51 mL/min
- Recovery from all reversible adverse events of previous anti-cancer therapies to baseline or CTCAE G 1, except for alopecia (any grade) and ≤ G 2 sensory peripheral neuropathy
- Able to swallow and retain oral drug
- Postmenopausal or evidence of non-childbearing status for women of childbearing potential prior to the first dose of study treatment. (negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as: Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments/Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the post menopausal range for women under 50/radiation-induced oophorectomy with last menses >1 year ago/chemotherapy-induced menopause with >1 year interval since last menses/surgical sterilisation (bilateral oophorectomy or hysterectomy)"
- Life expectancy > 16 weeks
- Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- As this study will include patients in France, a subject will be eligible for randomization in this study only if either affiliated to, or a beneficiary of, a social security category.

Critères de non-inclusion : - Patients with carcinosarcoma, neuro-endocrine and small cells histologies
- Patients who have previously received more than 1 line of chemotherapy for advanced/metastatic endometrial cancer
- Patients with a localized advanced disease that could be treated by surgery
- Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS)
- Patients with myelodysplastic syndrome/acute myeloid leukemia history or with features suggestive of MDS/AML.
- Patients receiving radiotherapy within 6 weeks prior to study treatment.
- Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
- Any previous treatment with PARP inhibitor, including olaparib.
- Clinically significant (e.g. active) cardiovascular disease, uncontrolled high blood pressure
- Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub- Arachnoids Hemorrhage (SAH) within 6 months prior to randomization.
- History or evidence of hemorrhagic disorders within 6 months prior to randomization
- Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
- Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
- Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
- Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) > grade 2) caused by previous cancer therapy, excluding alopecia.
- Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
- Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
- Pregnant or lactating woman
- Participation in another clinical study with an investigational product during he chemotherapy course immediately prior to randomization.
- Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
- Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
- Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
- Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
Informations relatives au promoteur
Promoteur :
Type de sponsor : Institutionnel
75004 PARIS 04

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre François BACLESSE - 3 avenue du Général Harris - 14000 CAEN
Apicrypt :

Investigateur :
Florence JOLY


Statut de l'essai : CLOS

MAJ : 07/10/2021