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)
60
2
3
48.5
30
0.6

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.

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 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
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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:
    No
    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

    Sponsors and Collaborators

    • National Taiwan University Hospital

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Taiwan University Hospital
    ClinicalTrials.gov Identifier:
    NCT05766410
    Other Study ID Numbers:
    • 202207200MIPB
    First Posted:
    Mar 13, 2023
    Last Update Posted:
    Mar 16, 2023
    Last Verified:
    Sep 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by National Taiwan University Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 16, 2023