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

NCT ID: NCT04753177

Last Updated: 2021-02-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-28
• Study Completion Date: 2024-01-28

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.

Conditions

The Neoadjuvant Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant combined hormone therapy

Ribocyclib, fulvestrant, triptorelin

Group Type: EXPERIMENTAL

Ribocyclib, fulvestrant, triptorelin

Intervention Type: DRUG

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

Doxorubicin, cyclophosphamide, paclitaxel

Intervention Type: DRUG

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

Chemotherapy (the control)

doxorubicin, cyclophosphamide, paclitaxel

Group Type: ACTIVE_COMPARATOR

Ribocyclib, fulvestrant, triptorelin

Intervention Type: DRUG

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

Doxorubicin, cyclophosphamide, paclitaxel

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary

St-Peterburg, , Russia

Countries

Russia

Other Identifiers

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Identifier Type: -

Identifier Source: org_study_id