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Cancer MetastaticPhase 3AMBRENCT04158362

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

A Phase 3 study testing Paclitaxel injection, Capecitabine tablets and Letrozole 2.5mg in people with Cancer Metastatic, run by UNICANCER at 2 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Cancer Metastatic
What is being tested?
Paclitaxel injection, Capecitabine tablets and Letrozole 2.5mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
180 participants
Where
2 sitesFrance
Study dates
11 Jun 2020to Jun 2032
Phase
Phase 3
Are there results?
Not yet: the study is under way

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 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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,
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  • 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
  • Platelets ≥100,000/mm³ or ≥100 x 10⁹/L
  • Hemoglobin ≥8 g/dL (patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion).
  • Serum Aspartate Transaminase (AST) and serum Alanine Aminotransferase Transaminase (ALT) ≤3 x upper limit of normal (ULN) (<5 ULN if liver metastasis)
  • Total serum bilirubin ≤1.5 x ULN (patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted)
  • Serum creatinine ≤1.5 x ULN or estimated creatinine clearance >60 mL/min as calculated using the standard method for the institution.
  • Women of childbearing potential agreeing to use highly effective contraception during treatment and for 3 weeks following the last dose of abemaciclib or for 6 months following the last dose of capecitabine or paclitaxel or for 2 years following the last dose of fulvestrant.
  • Women of childbearing potential must have a negative serum pregnancy test within 7 days and/or urine pregnancy test 48 hours prior to the administration of any study treatment.
  • Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
  • Health insurance coverage.

Who cannot join

  • 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.
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  • 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.
  • Patients with previously documented total/partial dihydropyrimidine dehydrogenase (DPD) deficiency or with DPD deficiency identified at baseline visit (plasma uracil concentration ≥16 ng/mL). These patients will be not eligible for chemotherapy by capecitabine.
  • Pregnant or breast feeding women.
  • Patients enrolled in another therapeutic study within 30 days prior inclusion.
  • Individuals deprived of liberty or placed under the authority of a tutor.

Trial locations and contacts

2 sites in 1 country.

France2 sites

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite, 69495

  • Centre Eugène Marquis

    Rennes

Other trials in France

About this study

Official title: 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

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.

Read the detailed description

The primary objective is to compare the efficacy of standard endocrine therapy + abemaciclib combination versus standard chemotherapy based on progression-free survival (PFS), in patients with visceral metastases of ER+/HER2- breast cancer and high tumor burden.

Patients will be randomly assigned to receive either:

  • Standard chemotherapy regimen physician's choice either (paclitaxel or capecitabine)
  • Standard endocrine therapy regimen physician's choice + abemaciclib (Letrozole or anastrozole for patients nonsteroidal aromatase inhibitor (NSAI) naïve or relapsing >1 year after the end of adjuvant endocrine therapy, and fulvestrant for patients relapsing on adjuvant or less than one year after completion of adjuvant NSAI)
Being tested
Paclitaxel injection, Capecitabine tablets, Letrozole 2.5mg, Anastrozole 1mg, Fulvestrant Prefilled Syringe
Keywords
Abemaciclib, Breast Cancer, High Burden Disease, Visceral Metastasis
Medical subject headings
Neoplasm Metastasis, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Paclitaxel injectionDrug

    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

  • Capecitabine tabletsDrug

    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

  • Letrozole 2.5mgDrug

    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.

  • Anastrozole 1mgDrug

    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.

  • Fulvestrant Prefilled SyringeDrug

    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.

  • AbemaciclibDrug

    Also called Verzenios®

    Oral 150 mg BID continuous

Study groups in NCT04158362
Study groupRoleWhat they receive
Standard Chemotherapy regimenExperimental* 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.
Receives: Drug: Paclitaxel injection; Drug: Capecitabine tablets
Standard Endocrine therapy (ET) regimen + AbemaciclibExperimental* 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.
Receives: Drug: Letrozole 2.5mg; Drug: Anastrozole 1mg; Drug: Fulvestrant Prefilled Syringe; Drug: Abemaciclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

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

    Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.

    The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.

    All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Measured: At baseline and every 6 weeks during 24 weeks

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

    This EORTC breast cancer specific questionnaire is intended to supplement the QLQ-C30.

    The QLQ-BR23 contains 23 items incorporating five multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning. In addition, single items assess sexual enjoyment, hair loss and future perspective. All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale. For all items but sexual functioning and sexual enjoyment, higher scores indicate more severe symptoms.

    Measured: At baseline and every 6 weeks during 24 weeks

  3. Patients' quality of life by the Quality of Life G8

    The G8 questionnaire is a 8-item screening tool developed specifically for older patients (>70 years old) leaving with cancer. This tool, addressed by the clinician, covers multiple domains, focusing on nutritional status, weight loss, body mass index, mobility, neuropsychological problems, medication use, self-rated health status, and age. The score ranges from 17 (not at all impaired) to 0 (heavily impaired).

    Measured: At baseline

  4. Objective response rate (ORR)

    The overall response rate (ORR) will be defined as the proportion of randomized patients who achieve a complete response (CR) or a partial response (PR) at 24 weeks.

    Measured: 24 weeks

  5. Duration of response (DoR)

    The duration of response (DoR) will be defined as the duration between the time of tumor response (CR or PR) until the date of objective progression.

    Measured: evey 8 weeks up to 48 months

  6. Progression-free-survival 1 (PFS1)

    PFS1 is defined as the interval between the date of randomization and the date of progression or death from any cause regardless of whether the patient withdraws from randomized study treatment or receives another anti-cancer therapy prior to progression.

    Measured: Throughout the study up to 48 months

  7. Progression-free-survival 2 (PFS2)

    PFS2 is defined as the time from the date of randomization to the earliest of the progression event subsequent to that used for the primary variable PFS, or date of death (i.e., objective radiological, CA15-3 or symptomatic progression).

    Measured: Throughout the study up to 48 months

  8. PFS1 and PFS2 in prespecified subgroups defined by stratification factors

    Stratification will be performed according to:

    1. Sensitivity to Endocrine therapy
    • endocrine sensitive = relapse >1 year after ending adjuvant endocrine therapy
    • endocrine resistance = relapse during or within 1 year after ending adjuvant endocrine therapy
    • de novo
    1. Planned chemotherapy (capecitabine versus paclitaxel)
    2. Liver metastasis Yes or No. Block randomization (ratio 1:1) will be stratified by the 12 (3*2*2) above-described groups

    Measured: Throughout the study up to 48 months

  9. Overall survival (OS)

    The overall survival is the length of time from randomization that patients endocrine therapy/abemaciclib improves overall survival compared to chemotherapy.

    Measured: From the date of randomization to the date of death from any cause, assessed up to 48 months

  10. Incidence of Treatment-Emergent Adverse Events

    The tolerance and safety will be evaluated by toxicity (acute [<6 months after the start of atezolizumab] and late [≥6 months after the start of atezolizumab]), assessed using the NCI CTCAE v5.0.

    Measured: Throughout study completion, up to 48 months

  11. Maintenance regimens after chemotherapy regimen

    Number of maintenance regimens administered after the end of the standard treatment by chemotherapy and in the absence of disease progression.

    Measured: 48 months

  12. Circulating tumor cell (CTC) count

    To study the predictive and prognostic value of circulating tumor cell count (<5 versus ≥ 5 CTC/7.5mL)

    Measured: At baseline

  13. Progression-free survival (PFS) within 24 weeks

    PFS within 24 months 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.

    Measured: From randomization to the date of the last available tumor assessment up to 24 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2019
  2. Study start11 Jun 2020
  3. Primary completion30 Apr 2025
  4. Study completionJun 2032 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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
Masking
None (open label)
Enrolment
180 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04158362
Sponsor's protocol ID
UC-0140/1901
Other IDs
2019-000260-14, 2019
Acronym
AMBRE
Status last verified
Jul 2026
First submitted
4 Nov 2019
Last updated
22 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Paclitaxel injection, Capecitabine tablets and Letrozole 2.5mg in people with Cancer Metastatic, run by UNICANCER at 2 sites in France.

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 24 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 22 Jul 2026. 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 France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: From randomization to the date of the first documented progression (RECIST v1.1) or death from any cause up to 48 months). 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 NCT04158362.

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 22 Jul 2026.

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