Endocrine Therapy With Abemaciclib or Chemotherapy as Initial Metastatic Treatment in ER+/HER2- Breast Cancer

NCT04158362 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: UC-0140/19012019-000260-14
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 2

Brief Summary

AMBRE is a phase III study comparing two standard treatments as initial metastatic treatment in ER+/HER2- breast cancer (BC) patients with visceral metastasis and high burden disease: Chemotherapy and combination of endocrine therapy with abemaciclib.

Conditions

Cancer Metastatic

Keywords

Abemaciclib; Breast Cancer; High Burden Disease; Visceral Metastasis

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS will be measured from the date of randomization until the date of event defined as the first documented progression (RECIST v1.1) or death from any cause.

  From randomization to the date of the first documented progression (RECIST v1.1) or death from any cause up to 48 months

Secondary Outcomes (13)

• Patients' quality of life by the Quality of life questionnaire - Core 30 (QLQ-C30)

  At baseline and every 6 weeks during 24 weeks

• Patients' quality of life by the Quality of Life Questionnaire - Breast cancer module (QLQ-BR23)

  At baseline and every 6 weeks during 24 weeks

• Patients' quality of life by the Quality of Life G8

  At baseline

• Objective response rate (ORR)

  24 weeks

• Duration of response (DoR)

  evey 8 weeks up to 48 months

Study Arms (2)

Standard Chemotherapy regimen

EXPERIMENTAL

\* Paclitaxel: administrated at the dose of 80 mg/m² as a 1-hour intravenous infusion every week (i.e., D1, D8 and D15) of a 3-week cycle. OR \* Capecitabine: given orally at a dose of 2000 to 2500 mg/m² daily for 14 days followed by a 7-day rest period every 3 weeks.

Drug: Paclitaxel injection; Drug: Capecitabine tablets

Standard Endocrine therapy (ET) regimen + Abemaciclib

EXPERIMENTAL

\* Letrozole: continuous orally administration of 2.5 mg/day (1 tablet/day) OR anastrozole continuous orally administration of 1 mg/day (1 tablet/day) in combination with oral abemaciclib 150 mg (BID: twice a day) continuous for patients NSAI naïve or relapsing \>1 year after the end of adjuvant ET. OR \* Fulvestrant: 500 mg intramuscular on D1-D15-D29 (loading dose). Then 500 mg every 28 days (maintenance dose) with oral abemaciclib 150 mg BID continuous for patients relapsing on adjuvant or less than one year after completion of adjuvant NSAI. For women with a non-menopausal status at inclusion, a concomitant Luteinizing hormone-releasing hormone (LH-RH) agonist will be administered in combination with ET every 28 days. The LH-RH agonist drug to be used will be left to the investigator's choice.

Drug: Letrozole 2.5mg; Drug: Anastrozole 1mg; Drug: Fulvestrant Prefilled Syringe; Drug: Abemaciclib

Interventions

Paclitaxel injection DRUG

Paclitaxel is administrated at the dose of 80 mg/m² as a 1-hour intravenous infusion every week (i.e., D1, D8 and D15) of a 3-week cycle

Standard Chemotherapy regimen

Capecitabine tablets DRUG

Capecitabine is given orally at a dose of 2000 to 2500 mg/m² daily for 14 days followed by a 7-day rest period every 3 weeks

Standard Chemotherapy regimen

Letrozole 2.5mg DRUG

Letrozole is administered orally at 2.5 mg/day continuous for patients nonsteroidal aromatase inhibitor naïve or relapsing \>1 year after the end of adjuvant endocrine therapy.

Standard Endocrine therapy (ET) regimen + Abemaciclib

Anastrozole 1mg DRUG

Anastrozole is administered orally at 1 mg/day continous for patients nonsteroidal aromatase inhibitor (NSAI) naïve or relapsing \>1 year after the end of adjuvant endocrine therapy.

Standard Endocrine therapy (ET) regimen + Abemaciclib

Fulvestrant Prefilled Syringe DRUG

Fulvestrant is administered at the dose of 500 mg intramuscular on D1-D15-D29 (as a loading dose), and then 500 mg every 28 days (as a maintenance dose) for patients relapsing on adjuvant or less than one year after completion of adjuvant NSAI.

Standard Endocrine therapy (ET) regimen + Abemaciclib

Abemaciclib DRUG

Oral 150 mg BID continuous

Also known as: Verzenios®

Standard Endocrine therapy (ET) regimen + Abemaciclib

Eligibility Criteria

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

You may qualify if:

• Patient must have signed a written informed consent form prior to any study specific procedures.
• Female age ≥ 18 years.
• Performance status, Eastern Cooperative Oncology Group (ECOG) 0-2.
• Histologically confirmed adenocarcinoma of the breast.
• Metastatic breast cancer, with liver and/or lung and/or pleural and/or peritoneal metastases with high tumor burden (according to RECIST v1.1) defined as either:
• visceral involvement of one site with more than 3 lesions,
• visceral involvement of at least 2 sites,
• symptomatic ascites or pleural effusion, defined as the need for weekly drainage with visceral measurable metastases,
• visceral involvement and lactate dehydrogenase (LDH) \> Normal value.
• Patient considered candidate for a first line chemotherapy in metastatic setting by their physician (either capecitabine or paclitaxel) and who may receive first-line endocrine therapy combined with abemaciclib according to the marketed authorization.
• ER-positive by immunohistochemistry (IHC) (\>10%) on primary or metastatic disease.
• HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish negative.
• Non-menopausal women will receive LH-RH agonists before starting the endocrine therapy and every 28 days thereafter. It is recommended that LH-RH agonist therapy be started approximately 28 days before the start of hormone therapy.
• Adequate renal, hepatic, and hematopoietic functions as defined by the following criteria:
• Absolute Neutrophil Count (ANC) ≥1,500/mm³ or ≥1.5 x 10⁹/L

You may not qualify if:

• Bone lesion only or non-measurable lesion (RECIST V1.1).
• Patients with all target lesions in a previously irradiated region, except if clear progression has been observed prior to study in at least one of them.
• Spinal cord compression and/or symptomatic or progressive brain metastases (Brain metastasis are not acceptable unless asymptomatic or treated and stable off steroids for at least 30 days prior to start of study drug).
• Patient with visceral crisis as defined in the 4th ESO-ESMO International Consensus Guidelines (severe organ dysfunction as assessed by signs and symptoms, laboratory studies and rapid progression of disease).
• Patient has received one line of chemotherapy for metastatic disease.
• Patient has received endocrine therapy for metastatic disease.
• Inability to swallow orally administered medication.
• Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and randomization.
• Major problem with intestinal absorption.
• Previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix or the breast, and adequately treated basal cell or squamous cell carcinoma of the skin.
• Patient has active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• Patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
• Patient has any serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30 mL/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• Any drug or plant derivative that may interact with abemaciclib.
• Episode of pulmonary thromboembolism (PTE) in the last six months. Patients with deep vein thrombosis previously treated with a low-molecular-weight heparin for more than two months prior enrolment in the study will be eligible.

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (2)

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre Eugène Marquis

Rennes, France

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Breast Neoplasms

Interventions

Paclitaxel; Capecitabine; Letrozole; Anastrozole; abemaciclib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitriles; Triazoles; Azoles

Study Officials

• Véronique DIERAS, Dr

  Centre Eugène Marquis, Rennes

  PRINCIPAL INVESTIGATOR

• Gilles FREYER, Pr

  Centre Hospitalier Lyon Sud

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, randomized, multicenter, phase III study, comparing standard chemotherapy to standard combination of endocrine therapy with abemaciclib as initial metastatic treatment among patients with visceral metastasis of ER+ HER2- breast cancer, high burden disease. Duration of one cycle of either treatment : 3 weeks

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 8, 2019
• Study Start: June 11, 2020
• Primary Completion: April 30, 2025
• Study Completion (Estimated): June 1, 2028
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.
• Access Criteria: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.

Locations

FR (2)