Etude : ULTIMATE /



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 : ULTIMATE

Nom :

Traitement : Néoadjuvant

Type d'étude : Ciblage moléculaire / Innovation thérapeutique

Dernière MÀJ : 27/05/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Etude internationale de phase II, évaluant la combinaison du durvalumab à l’hormonothérapie comme traitement néoadjuvant du cancer du sein invasif RO+/ Her2-, chez des patients qui présentent une infiltration de cellules T CD8+ après 4 à 6 semaines de traitement immuno-attractant

Spécialité : Seins, organes génitaux de la femme
Localisation : C50 - Tumeur maligne du sein
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : This is an open-label, multicentric, international, phase II trial testing aromatase inhibitors in combination with durvalumab in patients with CD8+ T cell infiltration (>10% CD8+ T cells in the tumor). The trial includes two sequences: The first part of the treatment will consist in 4-6 weeks treatment with immune-attractants; in the second part, CD8+ patients will receive 6 months of durvalumab combined with exemestane.

Phase : II

Stade : II à IV

NA
Critères d'inclusion
Critères de non-inclusion
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 1. Age ≥18 years post-menopausal according to one of the following criteria:
Age > 60 years
Or Bilateral ovariectomy
Or Age ≤ 60, with an uterus and presenting an amenorrhea of more than 12 months and FSH and estradiol in the postmenopausal range
Or Age ≤ 60, without an uterus and FSH and estradiol in the postmenopausal range
2. Histologically proven invasive breast cancer eligible to neoadjuvant endocrine therapy according to multidisciplinary tumor board;
Note: Multicentric/multifocal tumors are allowed if all share the same characteristics.
3. cT2-T4, any N; cT2 are eligible only if the clinical tumor size is > 3cm
4. Non metastatic, M0 (according to clinical staging);
5. Luminal A patients ER-positive by IHC according to the following criteria (local assessment): Grade I or II AND ER-positive (≥ 60%) AND Ki67 <20%;
6. Her2-negative by IHC (score 0 or 1+) and/or FISH/CISH negative according to local assessment;
7. CD8+ T Cell infiltration defined as >10% cells stained with anti-CD8 mAB by IHC at the 3- week biopsy (applicable for inclusion in part 2 only);
8. Available tumor samples from baseline biopsy;
9. World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrolment;
10. Adequate organ and marrow function as defined below:
Hemoglobin ≥9.0 g/dL
Absolute neutrophil count ≥1.5 × 109 /L
Platelet count ≥100 × 109 /L
Serum bilirubin ≤1.5 × the ULN. This will not apply to patients with confirmed Gilbert’s syndrome, who will be allowed in consultation with their physician.
ALT and AST ≤2.5 × ULN;
Adequate renal function as determined by CKD-EPI formula (using actual body weight)
11. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures;
12. Written informed consent obtained prior to performing any protocol-related procedures, including screening evaluations.

Critères de non-inclusion : 1. Inflammatory breast cancer
2. No prior exposure to immune-mediated therapy including, but not limited to, other antiCTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines;
3. Any concurrent chemotherapy, investigational product (IP), biologic therapy for cancer treatment;
4. Previous Radiotherapy treatment to more than 30% of the bone marrow;
5. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose;
6. History of allogenic organ transplantation;
7. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment;
8. Any condition that, in the opinion of the Investigator, would interfere with the evaluation of investigational product or interpretation of patient safety or study results, including ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events from investigational products, or compromise the ability of the patient to give written informed consent;
9. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) ≥470 ms;
10. History of active primary immunodeficiency;
11. Known history of active tuberculosis;
12. Active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
13. Current or prior use of immunosuppressive medication within 14 days before the first dose.
The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection).
- Systemic corticosteroids at physiologic doses not exceeding 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
14. Receipt of live, attenuated vaccine within 30 days prior to the first dose of IP.
Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP.
15. Known allergy or hypersensitivity to any medicinal product used in the trial or any excipient
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
Promoteur :
UNICANCER
Type de sponsor : Institutionnel
75654 Paris Cedex 13 - 75654 Paris Cedex 13
75001 PARIS 01

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 :
Christelle LEVY

TEC / ARC / IDE :
Sara GROSSI
s.grossi@
baclesse.unicancer.fr

Ouverture de l'essai : SUSPENDU

MAJ : 11/03/2019