Etude : VICTORIA /

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.

Type d'étude
Présentation de l'étude
Acronyme : VICTORIA

Nom :

Traitement : Métastatique ou localement avancé

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 05/11/2019
CIM10 - Localisation(s)
Informations principales
Titre : Etude multicentrique, randomisée en ouvert, de phase I/II évaluant un inhibiteur de mTOR (AZD2014) en association avec l’anastrozole versus anastrozole en monothérapie pour le traitement de patientes atteintes d’adénocarcinome de l’endomètre avec récepteurs hormonaux positifs en phase métastatique ou avancée

Spécialité : Seins, organes génitaux de la femme
Localisation : C54 - Tumeur maligne du corps de l'utérus
Informations complémentaires
Schéma : A Multicentric, Randomized, Non Comparative, Open-label Phase I/II Evaluating AZD2014 (Dual Mammalian Target of Rapamycin Complex 1/2 (mTORC1/mTORC2) Inhibitor) in Combination With Anastrozole Versus Anastrozole Alone in the Treatment of Metastatic Hormone Receptor-positive Endometrial Adenocarcinoma

2 arms:
- Experimental: Arm A: AZD2014 plus anastrozole
- Active Comparator: Arm B: anastrozole alone

Following randomisation patients will receive Arm A : AZD2014 plus anastrozole or Arm B: anastrozole alone AZD2014 will be administered with an intermittent schedule i.e. 125 mg bis in die (BID) intermittent with 2 days on followed by 5 days off per week for a total weekly dose of 500 mg/week (250mg D1 and D2, 5 days off) Anastrozole will be administered at the standard dose defined in the SPC i.e. 1mg/d, per os, continuously.
Both treatment will be administered until progressive disease (PD), unacceptable toxicity or willingness to stop.

Phase : I/II

Stade : NA

2, 3
Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Postmenopausal female patient at the time of consent
- Histologically-confirmed diagnosis of advanced or recurrent endometrial carcinoma, not amenable to curative treatments. Carcinosarcoma are not eligible.
- Documented estrogen receptor and/or progesterone receptor positive endometrial cancer. Hormone receptor positivity is defined according to routine practice at each participating site.
- Availability of a pre-treatment tumor sample (archival formalin-fixed paraffin-embedded (FFPE) block or fresh biopsy if feasible) and presence of at least one biopsiable tumor lesion for on-treatment biopsy
- Documented disease progression after no more than one prior first-line chemotherapy regimen and/or more than 2 lines endocrine therapy in the metastatic setting
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 and minimum life expectancy of 8 weeks
- At least one measurable lesion according to response evaluation criteria in solid tumor (RECIST 1.1)
- Adequate bone marrow, renal and liver function as shown by:
-> Absolute neutrophil count > 1.5 x 109/L, Platelets > 100 x 109/L, Hemoglobin (Hb) >9 g/dL
-> Serum bilirubin ≤ 1.5 upper limit of normal (ULN), alanine aminotransferase and aspartate aminotransferase ≤ 2.5 ULN (≤ 5 ULN in patients with liver metastases)
-> Creatinine clearance > 50 mL/min (using Cockcroft formula, or MDRD formula for patients over 65 years Appendix 3 - Creatinine Clearance)
- Fasting serum cholesterol ≤ 300 mg/dL (7.75 mmol/L) AND fasting triglycerides ≤ 2.5 ULN (lipid-lowering drugs allowed),
- Fasting plasma glucose ≤7 mmol/L (126 mg/dL)
- Recovered from prior significant treatment-related toxicity i.e. no persistent treatment-related toxicity > Grade 1 as per Common Terminology Criteria for Adverse Events (CTCAE) v4.3, except grade 2 alopecia, grade 2 anemia but with Hb >9 g/dL.
- Minimal wash-out period before the start of the study drugs for the following treatments:
-> Any anti-cancer treatment approved or investigational medicinal product :> 21 days
-> Any chemotherapy, radiation therapy, androgens : > 21 days (not including palliative radiotherapy at focal sites).
-> Any monoclonal antibody therapy: > 4 weeks
-> Major surgery: > 4 weeks
-> Minor surgery (excluding tumour biopsies) >14 days.
-> Any haemopoietic growth factors (e.g., filgrastim [granulocyte colony-stimulating factor (G-CSF)], sargramostim [granulocyte-macrophage colony-stimulating factor (GM-CSF)]): > 14 days
-> Vaccinated with live, attenuated vaccines : > 4 weeks.
-> Sensitive or narrow therapeutic range substrates of the drug metabolising organic anion-transporting polypeptide 1B1 (OATP1B1), organic anion-transporting polypeptide 1B3 (OATP1B3), MATE1 and MATE2K : see the appropriate wash-out period (a minimum of 5 x reported elimination half-life) in Appendix 5 - Restricted CYP and transporter related co-medications)
- Potent or moderate inhibitors or inducers of CYP3A4/5, Pgp (MDR1) and BCRP Restricted CYP and transporter related co-medications
- Patient willing to follow sunlight-protection measures. Patients should be advised of the need for sunlight protection measures during administration of AZD2014, and should be advised to adopt such measures for a period of 3 months after receiving their final dose of AZD2014.
- Patient able and willing to provide informed consent with ability to understand and willingness for follow-up visits.
- Covered by a medical insurance

Critères de non-inclusion : - Patient pre-treated by a non-steroidal aromatase inhibitor
- Active uncontrolled or symptomatic central nervous system metastases or spinal cord compression
- Clinically relevant abnormal levels of potassium or sodium.
- Use of any forbidden concomitant treatment during the treatment period:
-> Any anti-cancer treatment (approved or investigational) not mentioned in the protocol
-> Chronic treatment with corticosteroids or other immunosuppressive agents. Stable low dose of corticosteroids are allowed (unless contra-indicated) provided that they were initiated before the last disease progression or were started at least 4 weeks prior to study treatment. Topical or inhaled corticosteroids are allowed.
-> Potent or moderate inhibitors or inducers of CYP3A4/5, Pgp (MDR1) and BCRP (see Appendix 5 - Restricted CYP and transporter related co-medications)
-> Sensitive or narrow therapeutic range substrates of the drug transporters OATP1B1, OATP1B3, MATE1 and MATE2K outside the wash out period and restrictions presented in Appendix 5 - Restricted CYP and transporter related co-medications)
- Patient with known hypersensitivity to anastrozole or to any of the excipients (Lactose monohydrate, Povidone, Sodium starch glycollate, Magnesium stearate, Hypromellose, Macrogol 300, Titanium dioxide)
- History of hypersensitivity to active or inactive excipients of AZD2014 or drugs with a similar chemical structure or class to AZD2014
- History of other malignancies except for basal cell or squamous cell skin cancer, in situ cervical cancer, unless they have been disease-free for at least five years
- Patient who has any severe and/or uncontrolled medical conditions such as:
-> Recent history of specific cardiovascular events, or laboratory parameters that may affect cardiac parameters including : unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤6 months prior to start of study drug, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease; Symptomatic congestive heart failure of New York heart Association Class III or IV
-> Mean resting corrected QT interval (QTc), calculated using Fridericia's formula, > 470 msec obtained from 3 electrocardiograms (ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes within 12 months of the patient entering in the study
-> Abnormal cardiac function at baseline :left ventricular ejection fraction (LVEF) <50%
-> Any evidence of interstitial lung disease and uncompensated respiratory conditions.
-> Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active or chronic hepatitis (i.e. quantifiable hepatitis B virus (HBV-DNA) and/or positive HbsAg, quantifiable hepatitis C virus (HCV-RNA)),
-> Active, bleeding diathesis
-> Current refractory nausea and vomiting, chronic gastro-intestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD2014.
-> Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
-> Type 1 and uncontrolled Type 2 diabetes
-> Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis.
Informations relatives au promoteur
Promoteur :
Type de sponsor : Institutionnel
69003 LYON 03

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 : 27/08/2018