The Neoadjuvant Combined Hormone Therapy in Premenopausal Women With Locally Advanced ER+/HER2- Breast Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: The Neoadjuvant Therapy
• Intervention / Treatment: Drug: Ribocyclib, fulvestrant, triptorelin; Drug: Doxorubicin, cyclophosphamide, paclitaxel

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • St-Peterburg, Russian Federation, 191456
    • Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant combined hormone therapy; Ribocyclib, fulvestrant, triptorelin	Drug: Ribocyclib, fulvestrant, triptorelin; Neoadjuvant treatment will last 24 weeks in both groups. A follow-up examination will be carried out every 8 weeks. In the group of combined hormone therapy, repeate cor-biopsy of the tumor is planned to assess the Ki-67; Drug: Doxorubicin, cyclophosphamide, paclitaxel; Neoadjuvant treatment will last 24 weeks in both groups. A follow-up examination will be carried out every 8 weeks. In the group of combined hormone therapy, repeate cor-biopsy of the tumor is planned to assess the Ki-67
Active Comparator: Chemotherapy (the control); doxorubicin, cyclophosphamide, paclitaxel	Drug: Ribocyclib, fulvestrant, triptorelin; Neoadjuvant treatment will last 24 weeks in both groups. A follow-up examination will be carried out every 8 weeks. In the group of combined hormone therapy, repeate cor-biopsy of the tumor is planned to assess the Ki-67; Drug: Doxorubicin, cyclophosphamide, paclitaxel; Neoadjuvant treatment will last 24 weeks in both groups. A follow-up examination will be carried out every 8 weeks. In the group of combined hormone therapy, repeate cor-biopsy of the tumor is planned to assess the Ki-67

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
frequency of objective response	according to the results of ultrasound of the mammary glands and / or mammography	24 weeks
complete pathomorphological response	according to the Miller-Payne classification	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of the Ki67 level in postoperative material compared to primary biopsy	compared to primary biopsy	24 weeks
the frequency of organ-preserving operation after neoadjuvant treatment	in bouth groups	24 weeks
quality of life	The quality of life questionnaire EORTC QLQ-C30	24 weeks

Collaborators and Investigators

• Sponsor: Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2021
• Primary Completion (Anticipated): January 28, 2023
• Study Completion (Anticipated): January 28, 2024

Study Registration Dates

• First Submitted: February 6, 2021
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 15, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2021
• Last Update Submitted That Met QC Criteria: February 11, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: fulvestrant; combined hormone therapy; CDK4/6-ingibitors; gozerelin; triptorelin
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Luteolytic Agents; Cyclophosphamide; Paclitaxel; Fulvestrant; Doxorubicin; Triptorelin Pamoate
• Other Study ID Numbers: 12345 (Danish Center for Healthcare Improvements)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No