Breast CancerPhase 2ORACLE-RIPANCT05766410
A Randomized Study Comparing the Immune Modulation Effect of Ribociclib, Palbociclib, and Abemaciclib in ER+/HER2- EBC
A Phase 2 study testing Palbociclib, Ribociclib and Abemaciclib in people with Breast Cancer and Hormone Receptor-positive Breast Cancer, run by National Taiwan University Hospital at 2 sites in Taiwan.
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. Read more about this study
- Who is it for?
- Ages 20 years and older, women only
- Conditions the study is for
- Breast Cancer, Hormone Receptor-positive Breast Cancer, Hormone Therapy
- What is being tested?
- Palbociclib, Ribociclib and Abemaciclib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesTaiwan
- Study dates
- 16 Sep 2022to 30 Sep 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
Taiwan2 sites, 2 recruiting
- Recruiting
Department of Oncology, National Taiwan University Hospital
Taipei, 100
Yen-Shen Lu, MD, PhD, 886-2-23123456 ext. 67009, yslu@ntu.edu.tw
Yen-Shen Lu, MD, PhD
- Recruiting
Department of Oncology,National Taiwan University Hospital
Taipei, 100
Yen-Shen Lu, M.D.,Ph.D, 886-2-23123456 ext. 62859, yslu@ntu.edu.tw
I-Chun Chen, M.D.,Ph.D, 886-2-23123456 ext. 62859, A00523@ntucc.gov.tw
About this study
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
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.
Read the 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.
- Being tested
- Palbociclib, Ribociclib, Abemaciclib, Letrozole
- Keywords
- CDK4, 6 inhibitor, Neoadjuvant therapy, Hormone therapy, Hormone Receptor-positive Breast Cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PalbociclibDrug
Also called Ibrance
CDK4, 6 inhibitor
RibociclibDrug
Also called Kisqali
CDK4, 6 inhibitor
AbemaciclibDrug
Also called Venizio
CDK4, 6 inhibitor
LetrozoleDrug
Also called Femara
Endocrine therapy
| Study group | Role | What they receive |
|---|---|---|
| Palbociclib/Letrozole | Experimental | CDK4, 6 inhibitor and endocrine therapy Receives: Drug: Palbociclib; Drug: Letrozole |
| Ribociclib/Letrozole | Active comparator | CDK4, 6 inhibitor and endocrine therapy Receives: Drug: Ribociclib; Drug: Letrozole |
| Abemaciclib/Letrozole | Active comparator | CDK4, 6 inhibitor and endocrine therapy Receives: Drug: Abemaciclib; Drug: Letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
The expression of immune-related signature change after different CDK4/6 inhibitor treatments by RNAseq
Characterization of RNAseq from serial tumor biopsy samples
Measured: Through study completion, an average of 3 years
Secondary outcomes (1)
Adverse events
According to CTCAE 4.03
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2023
- Study start16 Sep 2022
- Primary completion30 Sep 2025 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yen-Shen Lu, MD, PhD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05766410
- Sponsor's protocol ID
- 202207200MIPB
- Acronym
- ORACLE-RIPA
- Status last verified
- Sep 2022
- First submitted
- 3 Feb 2023
- Last updated
- 16 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Zheng C, Pan Y, Zheng D, Pan Y. CDK4/6 inhibitors as conditional immune-priming agents in breast cancer: therapeutic windows, sequencing strategies, and rational combinations with immunotherapy, radiotherapy, and antibody-drug conjugates. Front Immunol. 2026 Aug 19;17:1934879. doi: 10.3389/fimmu.2026.1934879. eCollection 2026.
PubMed 42688140
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05766410
- Acronym / sponsor ID
- ORACLE-RIPA / 202207200MIPB
- Keywords
- CDK4, 6 inhibitor, Neoadjuvant therapy, Hormone therapy, Hormone Receptor-positive Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 16 Sep 2022 (actual)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 13 Mar 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Palbociclib/Letrozole | Experimental | Drug: Palbociclib, Drug: LetrozoleCDK4, 6 inhibitor and endocrine therapy |
| Ribociclib/Letrozole | Active comparator | Drug: Ribociclib, Drug: LetrozoleCDK4, 6 inhibitor and endocrine therapy |
| Abemaciclib/Letrozole | Active comparator | Drug: Abemaciclib, Drug: LetrozoleCDK4, 6 inhibitor and endocrine therapy |
Who may qualify
- Ages
- 20 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PalbociclibAlso: IbranceCDK4, 6 inhibitor | Drug | Palbociclib/Letrozole |
| RibociclibAlso: KisqaliCDK4, 6 inhibitor | Drug | Ribociclib/Letrozole |
| AbemaciclibAlso: VenizioCDK4, 6 inhibitor | Drug | Abemaciclib/Letrozole |
| LetrozoleAlso: FemaraEndocrine therapy | Drug | Abemaciclib/Letrozole, Palbociclib/Letrozole, Ribociclib/Letrozole |
Primary outcome
The expression of immune-related signature change after different CDK4/6 inhibitor treatments by RNAseq
Time frame: Through study completion, an average of 3 years
Characterization of RNAseq from serial tumor biopsy samples
1 secondary outcome
Adverse events
Time frame: 4 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2023.
- Derived from this study: PubMed 42688140Zheng C, Pan Y, Zheng D, Pan Y. CDK4/6 inhibitors as conditional immune-priming agents in breast cancer: therapeutic windows, sequencing strategies, and rational combinations with immunotherapy, radiotherapy, and antibody-drug conjugates. Front Immunol. 2026 Aug 19;17:1934879. doi: 10.3389/fimmu.2026.1934879. eCollection 2026.
Related trials for Breast Cancer
Not yet recruiting
Decision Support for Chemoprevention
Breast Cancer
Active, not recruiting
Improving Patient-Centered Communication in Breast Cancer Through Patient and Provider Interventions
Anatomic Stage 0 Breast Cancer AJCC v8, Anatomic Stage I Breast Cancer AJCC v8
Not yet recruitingPhase 2
The Impact of Using Nicorandil for the Prevention of Doxorubicin-Induced Cardiotoxicity
Doxorubicin Induced Cardiotoxicity, Doxorubicin Induced Cardiomyopathy
Not yet recruiting
Tolerability of Dalpiciclib vs. Abemaciclib/Ribociclib in Early HR+/HER2- Breast Cancer
Breast Cancer
Active, not recruitingObservational study
Assessment of Cognitive Function in Breast Cancer and Lymphoma Patients Receiving Chemotherapy
Breast Cancer, Lymphoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yen-Shen Lu, MD, PhD principal investigator
National Taiwan University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Palbociclib, Ribociclib and Abemaciclib in people with Breast Cancer and Hormone Receptor-positive Breast Cancer, run by National Taiwan University Hospital at 2 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yen-Shen Lu, MD, PhD (+886-2-23123456 ext. 67009, yslu@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The expression of immune-related signature change after different CDK4/6 inhibitor treatments by RNAseq (time frame: Through study completion, an average of 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05766410, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2023.