A Phase II Trial Testing Durvalumab Combined With Endocrine Therapy in Patients With ER+/Her2- Breast Cancer Eligible for Neoadjuvant Endocrine Therapy And Who Present CD8+ T Cell Infiltration After 4-6 Weeks Exposure to Immune-Attractant. - ULTIMATE

ICANCER0 sites61 target enrollmentStarted: October 31, 2017Last updated: April 19, 2022

Trial Snapshot

Phase: Phase 1
Status: Active, not recruiting
Sponsor
Enrollment: 61

Study Overview Eligibility Criteria Investigators Records & Identifiers Similar Trials

Study Overview

Brief Summary

No summary available.

Study Design

Study Type: Interventional clinical trial of medicinal product

Eligibility Criteria

Sex: All

Inclusion Criteria

•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.
•Are the trial subjects under 18? no
•Number of subjects for this age range:
•F.1.2 Adults (18-64 years) yes
•F.1.2.1 Number of subjects for this age range 8
•F.1.3 Elderly (>=65 years) yes
•F.1.3.1 Number of subjects for this age range 7

Exclusion Criteria

•1.Inflammatory breast cancer
•2. No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-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

Investigators

Sponsor

ICANCER

Similar Trials

Active, not recruiting

Phase 1

EUCTR2016-000764-42-FRICANCER

Active, not recruiting

Phase 1

EUCTR2017-001538-25-DEAIO-Studien-gGmbH128

Completed

Phase 2

on small cell lung cancer trial of durvalumab and tremelimumab in advanced epidermal growth factor receptor (EGFR) mutant disease.EGFR mutant advanced non small cell lung cancer.Cancer - Lung - Non small cell

ACTRN12618001742268niversity of Sydney100

Recruiting

Phase 2

Phase II study of Durvalumab (MEDI4736) plus Total Neoadjuvant Therapy (TNT) in locally advanced rectal cancer (The DUREC trial)

2024-515240-24-00Grupo Espanol Multidisciplinar En Cancer Digestivo60

Withdrawn

Phase 2

A prospective Phase II study of Durvalumab Rescue for Inadequate response to Lenalidomide and Dexamethasone in transplant ineligible patients with newly diagnosed multiple myelomaCancer - Myelomamultiple myeloma

ACTRN12617000958381Australia Myeloma Research Consortium137