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.
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)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
180
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 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 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.
Centre Hospitalier Lyon Sud
Pierre-Bénite, France
Centre Eugène Marquis
Rennes, France
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.
Time frame: From randomization to the date of the first documented progression (RECIST v1.1) or death from any cause up to 48 months
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.
Time frame: At baseline and every 6 weeks during 24 weeks
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.
Time frame: At baseline and every 6 weeks during 24 weeks
Patients' quality of life by the Quality of Life G8
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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 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.
Oral 150 mg BID continuous
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).
Time frame: At baseline
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.
Time frame: 24 weeks
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.
Time frame: evey 8 weeks up to 48 months
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.
Time frame: Throughout the study up to 48 months
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).
Time frame: Throughout the study up to 48 months
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 2. Planned chemotherapy (capecitabine versus paclitaxel) 3. Liver metastasis Yes or No. Block randomization (ratio 1:1) will be stratified by the 12 (3\*2\*2) above-described groups
Time frame: Throughout the study up to 48 months
Overall survival (OS)
The overall survival is the length of time from randomization that patients endocrine therapy/abemaciclib improves overall survival compared to chemotherapy.
Time frame: From the date of randomization to the date of death from any cause, assessed up to 48 months
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.
Time frame: Throughout study completion, up to 48 months
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.
Time frame: 48 months
Circulating tumor cell (CTC) count
To study the predictive and prognostic value of circulating tumor cell count (\<5 versus ≥ 5 CTC/7.5mL)
Time frame: At baseline
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.
Time frame: From randomization to the date of the last available tumor assessment up to 24 weeks.