Endocrine Therapy With Abemaciclib or Chemotherapy as Initial Metastatic Treatment in ER+/HER2- Breast Cancer (AMBRE)
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|ClinicalTrials.gov Identifier: NCT04158362|
Recruitment Status : Not yet recruiting
First Posted : November 8, 2019
Last Update Posted : December 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|Cancer Metastatic||Drug: Paclitaxel injection Drug: Capecitabine tablets Drug: Letrozole 2.5mg Drug: Anastrozole 1mg Drug: Fulvestrant Prefilled Syringe Drug: Abemaciclib||Phase 3|
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)
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||378 participants|
|Intervention Model:||Parallel Assignment|
|Intervention 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)|
|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|
|Estimated Study Start Date :||January 2020|
|Estimated Primary Completion Date :||June 2022|
|Estimated Study Completion Date :||June 2026|
Experimental: Standard Chemotherapy regimen
* 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.
* 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
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
Drug: Capecitabine tablets
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
Experimental: Standard Endocrine therapy (ET) regimen + Abemaciclib
* 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.
* 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.
Non-menopausal women will be included as soon as the reimbursement of abemaciclib in combination with ET will be approved for this population.
Drug: Letrozole 2.5mg
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.
Drug: Anastrozole 1mg
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.
Drug: Fulvestrant Prefilled Syringe
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
Other Name: Verzenios®
- Progression-free survival (PFS) within 24 weeks [ Time Frame: From randomization to the date of the last available tumor assessment up to 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.
- Patients' quality of life by the Quality of life questionnaire - Core 30 (QLQ-C30) [ Time Frame: At baseline and every 6 weeks during 24 weeks ]
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.
- Patients' quality of life by the Quality of Life Questionnaire - Breast cancer module (QLQ-BR23) [ Time Frame: At baseline and every 6 weeks during 24 weeks ]
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.
- Patients' quality of life by the Quality of Life G8 [ Time Frame: At baseline ]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).
- Objective response rate (ORR) [ Time Frame: 24 weeks ]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.
- Duration of response (DoR) [ Time Frame: evey 8 weeks up to 48 months ]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.
- Progression-free-survival 1 (PFS1) [ Time Frame: Throughout the study up to 48 months ]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.
- Progression-free-survival 2 (PFS2) [ Time Frame: Throughout the study up to 48 months ]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).
- PFS1 and PFS2 in prespecified subgroups defined by stratification factors [ Time Frame: Throughout the study up to 48 months ]
Stratification will be performed according to:
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
- Planned chemotherapy (capecitabine versus paclitaxel)
- Liver metastasis Yes or No. Block randomization (ratio 1:1) will be stratified by the 12 (3*2*2) above-described groups
- Overall survival (OS) [ Time Frame: From the date of randomization to the date of death from any cause, assessed up to 48 months ]The overall survival is the length of time from randomization that patients endocrine therapy/abemaciclib improves overall survival compared to chemotherapy.
- Incidence of Treatment-Emergent Adverse Events [ Time Frame: Throughout study completion, up to 48 months ]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.
- Maintenance regimens after chemotherapy regimen [ Time Frame: 48 months ]Number of maintenance regimens administered after the end of the standard treatment by chemotherapy and in the absence of disease progression.
- Circulating tumor cell (CTC) count [ Time Frame: At baseline ]To study the predictive and prognostic value of circulating tumor cell count (<5 versus ≥ 5 CTC/7.5mL)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04158362
|Contact: Mara BRIZARDemail@example.com|