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

Breast Cancer Clinical Trial

— ORACLE-RIPA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05766410
• Other study ID #: 202207200MIPB
• Status: Recruiting
• Phase: Phase 2
• Start date: September 16, 2022
• Est. completion date: September 30, 2026

Study information

• Verified date: September 2022
• Source: National Taiwan University Hospital
• Contact: Yen-Shen Lu, MD, PhD
• Phone: +886-2-23123456
• Email: yslu[@]ntu.edu.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 30, 2026
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Hormone Receptor-positive Breast Cancer
• Hormone Therapy

Intervention

Drug:
• Palbociclib
CDK4, 6 inhibitor
• Ribociclib
CDK4, 6 inhibitor
• Abemaciclib
CDK4, 6 inhibitor
• Letrozole
Endocrine therapy

Locations

Country	Name	City	State
Taiwan	Department of Oncology,National Taiwan University Hospital	Taipei
Taiwan	Department of Oncology, National Taiwan University Hospital	Taipei City

Sponsors (1)

Lead Sponsor	Collaborator
National Taiwan University Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The expression of immune-related signature change after different CDK4/6 inhibitor treatments by RNAseq	Characterization of RNAseq from serial tumor biopsy samples	Through study completion, an average of 3 years
Secondary	Adverse events	According to CTCAE 4.03	4 months