A Randomized Study Comparing the Immune Modulation Effect of Ribociclib, Palbociclib, and Abemaciclib in ER+/HER2- EBC

NCT ID: NCT05766410

Last Updated: 2023-03-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-16
• Study Completion Date: 2026-09-30

Brief Summary

The 3 FDA-approved CDK4, 6 inhibitors, palbociclib, ribociclib, and abemciclib, all provided progression-free survival benefits when combined with endocrine therapy in advanced ER+/HER2- breast cancer. But, not all of them provided overall survival benefit in the same setting. One of the proposed mechanisms that influence the overall survival difference is from the different influence of the 3 CDK4, 6 inhibitors on tumor microenvironment and/ or immune system. However, there was no head-to-head comparison of the 3 CDK4, 6 inhibitors in the same study. Neoadjuvant therapy provides a window to obtain tissue samples before treatment, during treatment, and after treatment. We aim to compare the immune modulation effects of palbociclib, ribociclib, and abemaciclib with letrozole in neoadjuvant treatment for ER+/HER2- early breast cancer.

Detailed Description

The 3 FDA-approved CDK4, 6 inhibitors, palbociclib, ribociclib, and abemciclib, all provided progression-free survival benefits when combined with endocrine therapy in advanced ER+/HER2- breast cancer. But, not all of them provided overall survival benefit in the same setting. One of the proposed mechanisms that influence the overall survival difference is from the different influence of the 3 CDK4, 6 inhibitors on tumor microenvironment and/ or immune system. However, there was no head-to-head comparison of the 3 CDK4, 6 inhibitors in the same study. Neoadjuvant therapy provides a window to obtain tissue samples before treatment, during treatment, and after treatment. We aim to compare the immune modulation effects of palbociclib, ribociclib, and abemaciclib with letrozole in neoadjuvant treatment for ER+/HER2- early breast cancer. We will collect tumor tissue, blood, and stool samples prospectively before treatment, at 2 weeks after treatment, and after 12 weeks of treatment at the time of surgery. Immune modulation effects will be compared between 3 treatment groups from breast tumor RNAseq analysis.

Conditions

Breast Cancer; Hormone Receptor-positive Breast Cancer; Hormone Therapy

Study Design

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

Study Groups

Palbociclib/Letrozole

CDK4, 6 inhibitor and endocrine therapy

Group Type: EXPERIMENTAL

Palbociclib

Intervention Type: DRUG

CDK4, 6 inhibitor

Letrozole

Intervention Type: DRUG

Endocrine therapy

Ribociclib/Letrozole

CDK4, 6 inhibitor and endocrine therapy

Group Type: ACTIVE_COMPARATOR

Ribociclib

Intervention Type: DRUG

CDK4, 6 inhibitor

Letrozole

Intervention Type: DRUG

Endocrine therapy

Abemaciclib/Letrozole

CDK4, 6 inhibitor and endocrine therapy

Group Type: ACTIVE_COMPARATOR

Abemaciclib

Intervention Type: DRUG

CDK4, 6 inhibitor

Letrozole

Intervention Type: DRUG

Endocrine therapy

Interventions

Palbociclib

CDK4, 6 inhibitor

Intervention Type: DRUG

Ribociclib

CDK4, 6 inhibitor

Intervention Type: DRUG

Abemaciclib

CDK4, 6 inhibitor

Intervention Type: DRUG

Letrozole

Endocrine therapy

Intervention Type: DRUG

Other Intervention Names

Ibrance; Kisqali; Venizio; Femara

Eligibility Criteria

Inclusion Criteria

• Female patients aged ≥ 20 years old at the time of informed consent.
• Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer based on the most recently analyzed tissue sample and all tested by local laboratory. with estrogen receptor positive (>10%) on IHC staining and HER2 negative (IHC 0+/1+, or IHC 2+ plus FISH negative)
• Stage II to III
• With adequate organ function
• ECOG 0-1

Exclusion Criteria

• Pregnant or nursing (lactating) women
• Women of child-bearing potential unless using highly effective methods of contraception during study drug dosing and for 12 months post-dosing
• Patients with active systemic infections or known to have AIDS or to test positive for HIV antibody at Screening
• Any other disease or condition that could interfere with participation in the study according to the study protocol, or with the ability of the patients to cooperate and comply with the study procedures.

• Minimum Eligible Age: 20 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yen-Shen Lu, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

Department of Oncology, National Taiwan University Hospital

Taipei, , Taiwan

Site Status: RECRUITING

Department of Oncology,National Taiwan University Hospital

Taipei, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Yen-Shen Lu, MD, PhD

Role: CONTACT

yslu@ntu.edu.tw

+886-2-23123456 ext. 67009

Facility Contacts

Yen-Shen Lu, MD, PhD

Role: primary

yslu@ntu.edu.tw

886-2-23123456 ext. 67009

Yen-Shen Lu, M.D.,Ph.D

Role: primary

yslu@ntu.edu.tw

886-2-23123456 ext. 62859

I-Chun Chen, M.D.,Ph.D

Role: backup

A00523@ntucc.gov.tw

886-2-23123456 ext. 62859

Other Identifiers

202207200MIPB

Identifier Type: -

Identifier Source: org_study_id