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

Sponsor

National Taiwan University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05766410

Collaborator

(none)

Enrollment

Locations

Arms

48.5

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Hormone Receptor-positive Breast Cancer Hormone Therapy	Drug: Palbociclib Drug: Ribociclib Drug: Abemaciclib Drug: Letrozole	Phase 2

Detailed Description

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

A Randomized, Open-label, Parallel-group Study Comparing the Immune Modulation Effect of Ribociclib, Palbociclib, and Abemaciclib in Early ER+/HER2- Breast Cancer

Actual Study Start Date :

Sep 16, 2022

Anticipated Primary Completion Date :

Sep 30, 2025

Anticipated Study Completion Date :

Sep 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Palbociclib/Letrozole CDK4, 6 inhibitor and endocrine therapy	Drug: Palbociclib CDK4, 6 inhibitor Other Names: Ibrance Drug: Letrozole Endocrine therapy Other Names: Femara
Active Comparator: Ribociclib/Letrozole CDK4, 6 inhibitor and endocrine therapy	Drug: Ribociclib CDK4, 6 inhibitor Other Names: Kisqali Drug: Letrozole Endocrine therapy Other Names: Femara
Active Comparator: Abemaciclib/Letrozole CDK4, 6 inhibitor and endocrine therapy	Drug: Abemaciclib CDK4, 6 inhibitor Other Names: Venizio Drug: Letrozole Endocrine therapy Other Names: Femara

Arm

Intervention/Treatment

Experimental: Palbociclib/Letrozole

CDK4, 6 inhibitor and endocrine therapy

Drug: Palbociclib

CDK4, 6 inhibitor

Other Names:

Ibrance

Drug: Letrozole

Endocrine therapy

Other Names:

Femara

Active Comparator: Ribociclib/Letrozole

CDK4, 6 inhibitor and endocrine therapy

Drug: Ribociclib

CDK4, 6 inhibitor

Other Names:

Kisqali

Drug: Letrozole

Endocrine therapy

Other Names:

Femara

Active Comparator: Abemaciclib/Letrozole

CDK4, 6 inhibitor and endocrine therapy

Drug: Abemaciclib

CDK4, 6 inhibitor

Other Names:

Venizio

Drug: Letrozole

Endocrine therapy

Other Names:

Femara

Outcome Measures

Primary Outcome Measures

The expression of immune-related signature change after different CDK4/6 inhibitor treatments by RNAseq [Through study completion, an average of 3 years]
Characterization of RNAseq from serial tumor biopsy samples

Secondary Outcome Measures

Adverse events [4 months]
According to CTCAE 4.03

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Oncology, National Taiwan University Hospital	Taipei City		Taiwan	100
2	Department of Oncology,National Taiwan University Hospital	Taipei		Taiwan	100