Abemaciclib Dose Escalation in Early High-Risk Breast Cancer Adjuvant Therapy

NCT07599137 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: BC-P40
• Study Type: interventional
• Target: 86
• Locations: 0 countries
• Sites: N/A

Brief Summary

Abemaciclib combined with endocrine therapy has become one of the important adjuvant treatment regimens for patients with HR+/HER2- high-risk early breast cancer. However, adverse events such as diarrhea, fatigue, neutropenia and elevated liver enzymes are concentrated in the early stage of adjuvant therapy, which often lead to dose reduction, temporary drug interruption or even permanent discontinuation. This further affects treatment adherence, relative dose intensity (RDI) and treatment completion rate. Findings from the TRADE study suggest that a step-up dosing strategy, initiating at a lower dose followed by gradual titration to the standard dose, combined with standardized patient education and symptomatic management, may improve early treatment tolerance, reduce the burden of partial toxicities, and increase the likelihood of patients achieving and maintaining abemaciclib 150 mg twice daily. Based on the above evidence and clinical experience, step-up dosing has been adopted by some clinicians for real-world clinical practice. Nevertheless, existing evidence is mainly derived from non-Chinese populations. There is still a lack of systematic real-world data on step-up dosing among Chinese breast cancer patients under routine outpatient management, including the early toxicity profile, dose escalation achievement rate at each stage, dose adjustment pathways (prolonged escalation, treatment pause or dose de-escalation), RDI distribution, correlation with quality of life, and baseline factors affecting treatment tolerance and dose target attainment. Therefore, it is necessary to conduct a real-world study focused on Chinese patients to fill the gap in local clinical evidence, and provide a basis for clinical pathway formulation, patient education, and subsequent multicenter validation studies.

Conditions

HR+/HER2- Breast Cancer

Keywords

breast cancer; Abemaciclib; Dose Escalation; side effect

Outcome Measures

Primary Outcomes (1)

• Rate of inadequate dosing

  Proportion of patients with inadequate dosing from postoperative treatment initiation to week 12

  From enrollment to the end of treatment at 12 weeks

Secondary Outcomes (2)

• Dose Target Attainment and Treatment Intensity

  From enrollment to the end of treatment at 12 weeks"

• QoL deterioration rate

  From enrollment to the end of treatment at 12 weeks.

Study Arms (1)

Dose escalation group

EXPERIMENTAL

Patients receiving postoperative abemaciclib step-up dosing regimen. Dose escalation schedule: 100 mg BID (Weeks 1-4), 100/150 mg daily (Weeks 5-8), 150 mg BID (Weeks 9-12).

Other: Dose escalation; Drug: Dose Escalation

Interventions

Dose Escalation OTHER

Patients receiving postoperative abemaciclib step-up dosing regimen. Dose escalation schedule: 100 mg BID (Weeks 1-4), 100/150 mg daily (Weeks 5-8), 150 mg BID (Weeks 9-12).

Dose escalation group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years;
• Pathologically confirmed breast cancer with ER and/or PR positive, HER2 negative;
• Completed radical mastectomy/radiacal breast surgery;
• Plan to receive abemaciclib combined endocrine therapy for at least 12 weeks, with abemaciclib administered via a step-up dosing regimen;
• ECOG performance status 0-1;
• Adequate organ function meeting medication requirements (routine blood test, liver and renal function, and other indicators consistent with clinical medication safety criteria);
• Signed written informed consent.

You may not qualify if:

• Previous exposure to any CDK4/6 inhibitor;
• Active infection or severe infection requiring systemic anti-infective treatment;
• Significant gastrointestinal diseases such as chronic diarrhea, inflammatory bowel disease, short bowel syndrome, which may affect drug absorption or increase the risk of diarrhea;
• Significant baseline hepatic or renal dysfunction, or uncontrolled severe comorbidities judged by the investigator to affect safety or treatment adherence;
• Pregnancy or lactation;
• Any other condition deemed ineligible for enrollment by the investigator.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Related Publications (4)

• Mayer EL, Trapani D, Kim SE, Faggen M, Sinclair N, Sanz-Altamira P, Battelli C, Berwick S, Lo S, Acevedo J, Sinclair S, Malcolm A, Varella L, Sammons S, Schumer S, Poorvu PD, Wallace E, Pasternak E, Tayob N, Tolaney SM. TRADE: a phase II trial to assess the tolerability of abemaciclib dose escalation in early-stage HR-positive/HER2-negative breast cancer. Ann Oncol. 2026 Jan;37(1):117-124. doi: 10.1016/j.annonc.2025.09.141. Epub 2025 Oct 17.

  PMID: 41110695 BACKGROUND

• Goetz MP, Cicin I, Testa L, Tolaney SM, Huober J, Guarneri V, Johnston SRD, Martin M, Rastogi P, Harbeck N, Shahir A, Wei R, Andre V, Rugo HS, O'Shaughnessy J. Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: analyses from the monarchE study. NPJ Breast Cancer. 2024 Apr 26;10(1):34. doi: 10.1038/s41523-024-00639-1.

  PMID: 38671001 BACKGROUND

• Johnston SRD, Toi M, O'Shaughnessy J, Rastogi P, Campone M, Neven P, Huang CS, Huober J, Jaliffe GG, Cicin I, Tolaney SM, Goetz MP, Rugo HS, Senkus E, Testa L, Del Mastro L, Shimizu C, Wei R, Shahir A, Munoz M, San Antonio B, Andre V, Harbeck N, Martin M; monarchE Committee Members. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023 Jan;24(1):77-90. doi: 10.1016/S1470-2045(22)00694-5. Epub 2022 Dec 6.

  PMID: 36493792 BACKGROUND

• Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, Zhang QY, Martinez Rodriguez JL, Campone M, Hamilton E, Sohn J, Guarneri V, Okada M, Boyle F, Neven P, Cortes J, Huober J, Wardley A, Tolaney SM, Cicin I, Smith IC, Frenzel M, Headley D, Wei R, San Antonio B, Hulstijn M, Cox J, O'Shaughnessy J, Rastogi P; monarchE Committee Members and Investigators. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987-3998. doi: 10.1200/JCO.20.02514. Epub 2020 Sep 20.

  PMID: 32954927 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Lize Wang, Doctor

CONTACT

+86-010-88197830; lize2010@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Breast Center

Study Record Dates

• First Submitted: May 7, 2026
• First Posted: May 20, 2026
• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share