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

  • STATUS
    Recruiting
  • End date
    Jun 26, 2028
  • participants needed
    378
  • sponsor
    UNICANCER
Updated on 26 May 2022
paclitaxel
cancer
direct bilirubin
endocrine therapy
serum bilirubin level
metastasis
neutrophil count
hormone therapy
liver metastasis
HER2
adenocarcinoma
fulvestrant

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.

Description

The primary objective is to compare the efficacy of standard endocrine therapy + abemaciclib combination versus standard chemotherapy based on progression-free survival (PFS) within 24 weeks, 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)

Details
Condition Cancer Metastatic
Treatment Abemaciclib, Paclitaxel injection, Letrozole 2.5mg, Anastrozole 1mg, Capecitabine tablets, Fulvestrant Prefilled Syringe
Clinical Study IdentifierNCT04158362
SponsorUNICANCER
Last Modified on26 May 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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-
ER-positive by immunohistochemistry (IHC) (>10%) on primary or metastatic disease
HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish negative
line endocrine therapy combined with abemaciclib according to the marketed
authorization
Adequate renal, hepatic, and hematopoietic functions as defined by the following
criteria
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
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
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
months following the last dose of capecitabine or paclitaxel or for 2 years
following the last dose of fulvestrant
Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
Health insurance coverage

Exclusion Criteria

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
Pregnant or breast feeding women
Patients enrolled in another therapeutic study within 30 days prior inclusion
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
Individuals deprived of liberty or placed under the authority of a tutor
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