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

• ClinicalTrials.gov Identifier: NCT04753177
• Recruitment Status: Active, not recruiting
• First Posted: February 15, 2021
• Last Update Posted: February 15, 2021
• Sponsor: Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary
• Information provided by (Responsible Party): Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary

Study Description

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.

Condition or disease	Intervention/treatment	Phase
The Neoadjuvant Therapy	Drug: Ribocyclib, fulvestrant, triptorelin; Drug: Doxorubicin, cyclophosphamide, paclitaxel	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Neoadjuvant Combined Hormone Therapy in Premenopausal Women With Locally Advanced ER+/HER2- Breast Cancer
• Actual Study Start Date: January 28, 2021
• Estimated Primary Completion Date: January 28, 2023
• Estimated Study Completion Date: January 28, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. frequency of objective response [ Time Frame: 24 weeks ]
   according to the results of ultrasound of the mammary glands and / or mammography
2. complete pathomorphological response [ Time Frame: 24 weeks ]
   according to the Miller-Payne classification

Secondary Outcome Measures :

1. change of the Ki67 level in postoperative material compared to primary biopsy [ Time Frame: 24 weeks ]
   compared to primary biopsy
2. the frequency of organ-preserving operation after neoadjuvant treatment [ Time Frame: 24 weeks ]
   in bouth groups
3. quality of life [ Time Frame: 24 weeks ]
   The quality of life questionnaire EORTC QLQ-C30

Eligibility Criteria

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

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

Contacts and Locations

Locations

Russian Federation

Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary

St-Peterburg, Russian Federation, 191456

Sponsors and Collaborators

Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary

More Information

• Responsible Party: Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary
• ClinicalTrials.gov Identifier: NCT04753177
• Other Study ID Numbers: 12345
• First Posted: February 15, 2021
• Last Update Posted: February 15, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: yes

• 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

Keywords provided by Saint Petersburg State Budgetary Healthcare Institution, City Clinical Oncology Dispensary:

combined hormone therapy; CDK4/6-ingibitors; fulvestrant; gozerelin; triptorelin

Additional relevant MeSH terms:

Paclitaxel; Cyclophosphamide; Doxorubicin; Fulvestrant; Triptorelin Pamoate; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Antineoplastic Agents, Hormonal; Estrogen Receptor Antagonists; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Luteolytic Agents; Contraceptive Agents, Female; Contraceptive Agents