Clinical trial NCT04753177: The Neoadjuvant Combined Hormone Therapy in Premenopausal Women With Locally Advanced ER+/HER2- Breast Cancer
Official title: The Neoadjuvant Combined Hormone Therapy in Premenopausal Women With Locally Advanced ER+/HER2- Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: The Neoadjuvant Therapy
Keywords: combined hormone therapy
CDK4/6-ingibitors
fulvestrant
gozerelin
triptorelin
Lead sponsor: Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary
Sponsor class: OTHER
First posted: 2021-02-15
Enrollment: 120
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Breast cancer take a leading position in the structure of morbidity and mortality from malignant tumors among women.

Today the interest of many scientists and pharmaceutical companies is focused on the study of metastatic breast cancer forms. While we obtain little experimental data and practical research about the treatment of locally advanced forms.

In this regard, the study of new neoadjuvant drug therapy regimen for estrogen-receptor positive breast cancer in premenopausal woman is very relevant.

The proposed research will be the absolutely innovative investigation worldwide.

The study will consist of two modes of treatment, combined hormone therapy with CDK4/6-ingibitors and chemotherapy (the control), each replicated four times in a randomized, complete block design.

This research aims to improve the results of treatment, namely to increase the percentage of successfully treated patients and reduce toxicity from treatment.

Primary study endpoints will include the frequency of objective response and complete pathomorphological response (according to the Miller-Payne classification).

Secondary endpoints will include a decrease of the Ki67 level in postoperative material compared to primary biopsy, the frequency of organ-preserving operation after neoadjuvant treatment and quality of life.

Study hypothesis: neoadjuvant combined hormone therapy with CDK4/6-ingibitors in premenopausal women with luminal breast cancer leads to at least the same results as neoadjuvant chemotherapy, but with less toxicity.


Eligibility criteria: Inclusion Criteria:

* Female
* Age ≥ 18 years
* Women with a newly diagnosed breast cancer who have not previously received specific treatment, with a tumor stage: cT1-3N1-2M0.
* Immunohistochemical tumor markers: ER-positive (ER+ is defined ≥ 10% and/or and Allred of 2 or more); HER2 negative (HER2 negative is defined as having an IHC of 1+ without ISH OR IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number \< 4 signals/cells OR ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number \< 4 signals/cells (without IHC)
* Premenopausal women.
* Signed consent to participate in a clinical trial.
* The consent of the patient to carry out, if possible, organ-preserving surgery with previous radiation therapy.
* General state of ECOG (PS) 0 or 1.
* Adequate Bone Marrow Function including:

Absolute Neutrophil Count (ANC) ≥1500/μL or ≥1.5 x109/L; Platelets ≥100000/μL or ≥100 x 109/L; Hemoglobin ≥ 9 g/dL.

* Adequate Renal Function including: Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated creatinine clearance ≥ 60 ml/min as calculated using the method standard for the institution.
* Adequate Liver Function, including all of the following parameters:

Total serum bilirubin ≤ 1.0 x ULN unless the subject has documented Gilbert syndrome (in which case up to 3 x ULN is acceptable) ; Aspartate and Alanine Aminotransferase (AST and ALT) ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN.

* Female subjects of child bearing potential and their partners, who are sexually active, must agree to the use of two highly effective forms of contraception in combination throughout the period of taking study treatment and for at least 90 days after last dose of study drug, or they must totally/truly abstain from any form of sexual intercourse. Use of oral hormonal contraceptive agents in this study is not permitted.
* Absence of mutations in the BRCA1 and BRCA2 genes (revealed by PCR blood analysis)
* Providing histological materials to determine the status of mutations in the PIK3CA gene

Exclusion Criteria:

* Primary multiple synchronous tumors (except for detected basal multiple cancer of the skin or cervix in situ, which can be radically treated without adjuvant treatment for breast cancer)
* HIV positive status
* Known hypersensitivity to study drugs or excipients.
* Pregnancy and lactation
* Any chronic disease in the acute stage

Primary outcomes:
measure: frequency of objective response
timeFrame: 24 weeks
measure: complete pathomorphological response
timeFrame: 24 weeks
Secondary outcomes:
measure: change of the Ki67 level in postoperative material compared to primary biopsy
timeFrame: 24 weeks
measure: the frequency of organ-preserving operation after neoadjuvant treatment
timeFrame: 24 weeks
measure: quality of life
timeFrame: 24 weeks
Other outcomes:
Locations:
city: St-Peterburg
country: Russian Federation
facility: Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary
Study officials:
References: