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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Hormone Receptor-positive Breast Cancer; Hormone Therapy
• Intervention / Treatment: Drug: Palbociclib; Drug: Letrozole; Drug: Ribociclib; Drug: Abemaciclib

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • Department of Oncology,National Taiwan University Hospital
    • Contact: Yen-Shen Lu, M.D.,Ph.D; Phone Number: 62859 886-2-23123456; Email: yslu@ntu.edu.tw
    • Contact: I-Chun Chen, M.D.,Ph.D; Phone Number: 62859 886-2-23123456; Email: A00523@ntucc.gov.tw
    • Sub-Investigator: Ching-Hung Lin, M.D.,Ph.D
    • Sub-Investigator: Dwan-Ying Chang, M.D.
    • Sub-Investigator: Tom Wei-Wu Chen, M.D.,Ph.D
    • Sub-Investigator: I-Chun Chen, M.D.,Ph.D
    • Sub-Investigator: Ming-Yang Wang, M.D.,Ph.D
    • Sub-Investigator: Wei-Li Ma, M.D.
    • Principal Investigator: Yen-Shen Lu, M.D.,Ph.D
  • Taipei City, Taiwan, 100
    • Recruiting
    • Department of Oncology, National Taiwan University Hospital
    • Sub-Investigator: Ching-Hung Lin, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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: Letrozole; Endocrine therapy; Other Names: Femara; Drug: Ribociclib; CDK4, 6 inhibitor; Other Names: Kisqali
Active Comparator: Abemaciclib/Letrozole; CDK4, 6 inhibitor and endocrine therapy	Drug: Letrozole; Endocrine therapy; Other Names: Femara; Drug: Abemaciclib; CDK4, 6 inhibitor; Other Names: Venizio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	According to CTCAE 4.03	4 months

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Yen-Shen Lu, MD, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2022
• Primary Completion (Anticipated): September 30, 2025
• Study Completion (Anticipated): September 30, 2026

Study Registration Dates

• First Submitted: February 3, 2023
• First Submitted That Met QC Criteria: March 2, 2023
• First Posted (Actual): March 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Neoadjuvant therapy; Hormone therapy; Hormone Receptor-positive Breast Cancer; CDK4, 6 inhibitor
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole; Palbociclib
• Other Study ID Numbers: 202207200MIPB

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No