NCT04293393

Neoadjuvant Study Chemotherapy vs Letrozole + Abemaciclib in HR+/HER2- High/Intermediate Risk Breast Cancer Patients

Phase II, Randomized, Open-label, International, Multicenter Study to Compare Efficacy of Standard Chemotherapy vs. Letrozole Plus Abemaciclib as Neoadjuvant Therapy in HR-positive/HER2-negative High/Intermediate Risk Breast Cancer Patients

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (actual)
• Sponsor: Spanish Breast Cancer Research Group · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Phase II, randomized, open-label, international, multicenter study to compare efficacy of standard chemotherapy vs. letrozole plus abemaciclib as neoadjuvant therapy in HR-positive/HER2-negative high/intermediate risk breast cancer patients

Detailed description

This is an international, multicenter, open-label, randomized phase II study in the neoadjuvant setting. Approximately 200 premenopausal and postmenopausal women with Hormone Receptor (HR)-positive/Human Epidermal Growth Factor Receptor 2 (HER2) negative Breast Cancer (BC) of intermediate/high risk determined by Ki67 index ≥ 20% on untreated breast tissue and centrally assessed, with indication of neoadjuvant treatment, will be included. Patients with Early Breast Cancer (EBC) on stages II-III (tumor size (T) \> 2cm - T3, T4b, and lymph node involvement (N) N0-2) according to the 8th edition of the Union for International Cancer Control (UICC) TNM Classification. The subgroup with tumors T2 N0 will include high risk patients based on Ki67 index \> 30% or Ki67 index between 20% and 30% and Progesterone Receptor (PgR) negative and/or histological grade 3. Patients will be stratified according to the disease stage (II vs. III), menopausal status (premenopausal vs. postmenopausal) and Ki67 index (Ki67 \< 30% vs. Ki67 ≥ 30%). Once the screening process (locally at site and at the central laboratory) is completed, fully eligible patients will be randomized in a 1:1 fashion to the control arm with standard Chemotherapy (CT) based on anthracyclines and taxanes or to the experimental arm with letrozole + abemaciclib. All patients will be treated according to the stipulations below, unless any of the following occur: unacceptable toxicity, progressive disease, or withdrawal of informed consent, whatever occurs first. After the last dose of any of the drugs in the neoadjuvant combinations, in both treatment arms definitive surgery will be performed. For Arm A not earlier than 21 days and not later than 42 days after the last dose of chemotherapy, and for Arm B within 7 days from the last dose of abemaciclib and/or letrozole, unless toxicities are not recovered completely in any treatment arm.

Conditions

• Early Breast Cancer

Interventions

Type	Name	Description
DRUG	Doxorubicin	Doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 (AC) every 21 days for 4 cycles followed by weekly paclitaxel 80mg/m2 for 12 weeks or 3-weekly docetaxel 100mg/m2 for 4 cycles.
DRUG	Cyclophosphamide	Doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 (AC) every 21 days for 4 cycles followed by weekly paclitaxel 80mg/m2 for 12 weeks or 3-weekly docetaxel 100mg/m2 for 4 cycles.
DRUG	Taxane	Doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 (AC) every 21 days for 4 cycles followed by weekly paclitaxel 80mg/m2 for 12 weeks or 3-weekly docetaxel 100mg/m2 for 4 cycles.
DRUG	Letrozole	Letrozole 2.5mg orally daily + abemaciclib 150mg orally every 12 hours on a continuous dosing schedule, +/- LHRH analogs in premenopausal women, up to 12 months, in 28-day cycles
DRUG	Abemaciclib	Letrozole 2.5mg orally daily + abemaciclib 150mg orally every 12 hours on a continuous dosing schedule, +/- LHRH analogs in premenopausal women, up to 12 months, in 28-day cycles
DRUG	LHRH Analogue	Letrozole 2.5mg orally daily + abemaciclib 150mg orally every 12 hours on a continuous dosing schedule, +/- LHRH analogs in premenopausal women, up to 12 months, in 28-day cycles

Timeline

• Start date: 2020-10-02
• Primary completion: 2023-06-21
• Completion: 2033-02-28
• First posted: 2020-03-03
• Last updated: 2026-03-12
• Results posted: 2026-03-12

Locations

28 sites across 1 country: Spain