Etude : Eudario /



ATTENTION : pour chaque essai clinique, les éléments affichés ci-dessous ne sont pas exhaustifs, et le protocole fourni par le promoteur reste l’unique document à consulter pour mener à bien un essai clinique sur centre. Pour plus d'informations, contactez le référent du territoire concerné.


Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : Eudario

Nom :

Traitement : Adjuvant

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 25/11/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Etude de phase II, multicentrique, en ouvert, randomisée en 3 bras, évaluant l'innocuité et l'efficacité de l'inhibiteur de HSP90 Ganetespib, en association avec du carboplatine, suivi d'un traitement d'entretien au Niraparib versus Ganetespib plus carboplatine suivi de Ganetespib et de Niraparib versus Carboplatine en association avec la chimiothérapie standard, suivi par un traitement d'entretien par Niraparib chez les patientes atteintes d'un cancer de l'ovaire sensible au platine

Spécialité : Seins, organes génitaux de la femme
Localisation : C56 - Tumeur maligne de l'ovaire

Spécialité : Seins, organes génitaux de la femme
Localisation : C57 - Tumeur maligne des organes génitaux de la femme, autres et non précisés

Spécialité : Tissu mésothélial et tissus mous
Localisation : C48 - Tumeur maligne du rétropéritoine et du péritoine
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : This study will be performed in women with platinum-sensitive, high-grade serous, high-grade endometrioid, undifferentiated epithelial ovarian cancer, carcinosarcoma, fallopian tube or primary peritoneal cancer (proven by central histo-pathological review).

A total of 120 subjects will be randomized (1:1:1) to three different treatment arms: (A) Standard arm (arm A): Carboplatin (AUC5 d1, q3w i.v.) in combination with Paclitaxel (175 mg/m² d1, q3w i.v.) or Carboplatin (AUC4 d1, q3w i.v.) in combination with Gemcitabine (1000 mg/m² d1, d8, q3w i.v.) followed by maintenance therapy with Niraparib (200/ 300 mg oral daily, q4w) // (B) First experimental arm (arm B): Ganetespib (150 mg/m2, d1, q3w) in combination with Carboplatin (AUC5 d1, q3w i.v.) followed by maintenance treatment with Niraparib (200/ 300 mg oral daily, q4w) // (C) Second experimental arm (arm C): Ganetespib (150 mg/m² d1, q3w i.v.) plus Carboplatin (AUC5 d1, q3w i.v.) followed by Ganetespib (100 mg/m² d1, d8, d15, d22, q4w i.v.) and Niraparib (200 mg oral daily, q4w).

Chemotherapy treatment will be given for 6 cycles, maintenance treatment with Ganetespib will be given for a maximum of 9 months or until disease progression, maintenance treatment with Niraparib can continue until disease progression.

Phase : II

Stade : Localement avancé à Métastasique

2, 3, 4, X
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 :

Patients must meet the following criteria to be eligible for study entry:
Ability to understand and willingness to sign and date a written informed consent document
Female patients ≥18 years of age
High-grade serous, high-grade endometrioid, undifferentiated epithelial ovarian cancer, carcinosarcoma, fallopian tube or primary peritoneal cancer
Platinum-sensitive relapse >6months after previous platinum-based treatment (calculated from the first day of the last cycle of the last platinum-based chemotherapy until the date of progression confirmed according to RECIST 1.1 on imaging)
No limits in number of prior lines
Measurable or evaluable disease according to RECIST 1.1
ECOG performance status 0-1
Adequate functions of the bone marrow
Platelets ≥ 100 x 109/L

Absolute neutrophil count (ANC) ≥ 1.5 x 109/L

• Adequate function of the organs
Creatinine < 2 mg/dl (<177 μmol/L)
Total bilirubin ≤ 1.5 x upper limit of normal (≤ 2.0 in patients with known Gilberts syndrome) OR direct bilirubin ≤ 1 x ULN
SGOT/SGPT (AST/ALT) ≤ 2.5 x upper limit of normal unless liver metastases are present, in which case they must be ≤ 5 x ULN

Urinanalysis or urine dipstick for proteinuria less than 2+. Patients with ≥ 2+ on dipstick should undergo 24-hour urine collection and must demonstrate < 1 g of protein/24 hours; except the proteinuria is clearly related to a catheter in the urinary system.
Adequate coagulation parameter: aPTT ≤ 1.5 x ULN (patients on heparin treatment must have an aPTT between 1.5-2.5 x ULN), or INR ≤ 1.5. (In patients receiving anticoagulants (such as warfarin) INR must be between 2.0 and 3.0 in two consecutive measurements 1-4 days apart).
Participant receiving corticosteroids (dose < 10 mg/day methylprednisolone equivalent), including inhaled steroids, may continue as long as their dose is stable for at least 4 weeks prior to initiating protocol therapy.
Participants must agree to not donate blood during the study or for 90 days after the last dose of study treatment
Female participant has a negative serum pregnancy test within 7 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of non-childbearing potential. Non-childbearing potential is defined as follows (by other than medical reasons):
≥ 45 years of age and has not had menses for >1 year
Patients who have been amenorrhoeic for < 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by imaging. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. See below for a list of acceptable birth control methods. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.

Birth Control: Participants of childbearing potential who are sexually active and their partners must agree to the use of a highly effective form of contraception throughout their participation beginning with time of consent, during the study treatment and for 180 days after last dose of study treatment(s):

Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
Oral route
Intravaginal route
Transdermal route

Progestogen-only hormonal contraception associated with inhibition of ovulation
Oral
Injectable
Implantable
Intrauterine device
Intrauterine hormone-releasing system
Bilateral tubal occlusion
Vasectomized partner

Sexual abstinence, if the preferred and usual lifestyle of the subject
Participant must agree to not breastfeed (or store breast milk for use) during the study or for 180 days afer the last dose of study treatment.
Haemoglobin ≥8.5 g/dl (patients may not receive a transfusion within 4 weeks prior to initiating study treatment)
Able to take oral medications
Availability of archival ovarian cancer tissue from primary diagnosis (delivery of FFPE block or slides is prerequisite for randomisation)

Critères de non-inclusion :

Patients who meet any of the following criteria will be excluded from study entry:
Ovarian tumours with low malignant potential (i.e. borderline tumours)
Any prior radiotherapy to the pelvis or abdomen, or any radiotherapy encompassing > 20 % of the bone marrow within 2 weeks, or any radiotherapy within 1 week prior to Day 1 of protocol therapy
Surgery (including open biopsy and traumatic injury) within 4 weeks prior to first dose of Ganetespib, or anticipation of the need for major surgery during study treatment
Minor surgical procedures, within 24 hours prior to the first study treatment
Known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

Any serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, chronic obstructive pulmonary disease, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.

Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (>325 mg/day).
Patients with a history of diagnosis, detection or treatment of any prior malignancies ≤ 2 years prior to initiating protocol therapy, except: basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated.
Clinically significant gastro-intestinal (GI) tract abnormalities that may increase the risk for GI bleeding and / or perforation including but not limited to: active peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding; inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), history of bowel obstruction within 1 year prior to first study treatment (excluding postoperative, i.e. within 4 weeks post surgery), other GI condition with increased risk of perforation such as recurrence deeply infiltrating into the muscularis or mucosa of the rectosigmoid or the mucosa of the bladder, or history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
Non-healing wound or non-healing bone fracture
Patients with symptomatic brain or leptomeningeal metastases (patients who are asymptomatic since treatment of brain or leptomeningeal metastases, eg. after irradiation, are eligible)
Left ventricular ejection fraction (LVEF) defined by ECHO below the institutional lower limit of normal
Cerebrovascular accident (CVA)/ stroke or transient ischemic attack (TIA) or sub-arachnoid haemorrhage within ≤ 6 months prior to first study treatment.
Significant cardiac disease: New York Heart Association (NYHA) Class 3 or 4; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty or coronary atrial or ventricular cardiac arrhythmias
History of prolonged QT syndrome, or family member with prolonged QT syndrome
QTc interval > 470 msec when 3 consecutive ECG values are averaged
Ventricular tachycardia or a supraventricular tachycardia that requires treatment with a Class Ia antiarrhythmic drug (e.g. sotalol, amiodarone, dofetilide). Use of other antiarrhythmic drugs is permitted
Second- or third-degree atrioventricular (AV) block, except: treated with a permanent pacemaker Complete left bundle branch block (LBBB)
History of evidence of haemorrhagic disorders, patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorders, coagulopathy or tumour involving major vessels.
Participation in another clinical study with experimental therapy within 28 days before start of treatment.
Participant must not be simultaneously enrolled in any interventional clinical trial.
Women who are pregnant or are lactating
Patients unable to be regularly followed for any reason (geographic, familiar, social, psychologic, housed in an institution eg. prison because of a court agreement or administrative order)
Subjects that are dependent on the sponsor/CRO or investigational site as well as on the investigator.
History of known hypersensibility against any medication used in the study
Intolerance / Hypersensitivity reactions to components and excipients of study drugs
Peripheral neuropathy of grade >2 per NCI CTCAE, version 4.03, within 4 weeks prior to randomisation
Any other condition that, in the opinion of the investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03783949
Promoteur :
Universitaire Ziekenhuizen Leuven
Type de sponsor : Institutionnel
Collaborateur : European Commission
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre François BACLESSE - 3 avenue du Général Harris - 14000 CAEN

Investigateur :
Florence JOLY

TEC / ARC / IDE :
Astrid LETIEMBRE
a.letiembre@
baclesse.unicancer.fr

Ouverture de l'essai : OUVERT

MAJ : 25/11/2019