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

Primary Purpose

Cancer Metastatic

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Paclitaxel injection
Capecitabine tablets
Letrozole 2.5mg
Anastrozole 1mg
Fulvestrant Prefilled Syringe
Abemaciclib
Sponsored by
UNICANCER
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cancer Metastatic focused on measuring Abemaciclib, Breast Cancer, High Burden Disease, Visceral Metastasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patient must have signed a written informed consent form prior to any study specific procedures.
  2. Female age ≥ 18 years.
  3. Performance status, Eastern Cooperative Oncology Group (ECOG) 0-2.
  4. Histologically confirmed adenocarcinoma of the breast.
  5. 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.
  6. 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.
  7. ER-positive by immunohistochemistry (IHC) (>10%) on primary or metastatic disease.
  8. HER2-negative by IHC (score 0 or 1+) and/or Fish/Cish negative.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
  14. Health insurance coverage.

Exclusion Criteria:

  1. Bone lesion only or non-measurable lesion (RECIST V1.1).
  2. 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.
  3. 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).
  4. 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).
  5. Patient has received one line of chemotherapy for metastatic disease.
  6. Patient has received endocrine therapy for metastatic disease.
  7. Inability to swallow orally administered medication.
  8. 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.
  9. Major problem with intestinal absorption.
  10. 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.
  11. 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.
  12. 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.
  13. 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).
  14. Any drug or plant derivative that may interact with abemaciclib.
  15. 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.
  16. 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.
  17. Pregnant or breast feeding women.
  18. Patients enrolled in another therapeutic study within 30 days prior inclusion.
  19. Individuals deprived of liberty or placed under the authority of a tutor.

Sites / Locations

  • Centre Hospitalier Lyon SudRecruiting
  • Centre Eugène MarquisRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Standard Chemotherapy regimen

Standard Endocrine therapy (ET) regimen + Abemaciclib

Arm Description

* 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.

* 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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).
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.
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.
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.
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).
PFS1 and PFS2 in prespecified subgroups defined by stratification factors
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)
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
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
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
To study the predictive and prognostic value of circulating tumor cell count (<5 versus ≥ 5 CTC/7.5mL)

Full Information

First Posted
November 4, 2019
Last Updated
May 11, 2022
Sponsor
UNICANCER
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1. Study Identification

Unique Protocol Identification Number
NCT04158362
Brief Title
Endocrine Therapy With Abemaciclib or Chemotherapy as Initial Metastatic Treatment in ER+/HER2- Breast Cancer
Acronym
AMBRE
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 11, 2020 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
June 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNICANCER

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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) 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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer Metastatic
Keywords
Abemaciclib, Breast Cancer, High Burden Disease, Visceral Metastasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
378 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard Chemotherapy regimen
Arm Type
Experimental
Arm Description
* 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.
Arm Title
Standard Endocrine therapy (ET) regimen + Abemaciclib
Arm Type
Experimental
Arm Description
* 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.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel injection
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Capecitabine tablets
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Letrozole 2.5mg
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Anastrozole 1mg
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Fulvestrant Prefilled Syringe
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Abemaciclib
Other Intervention Name(s)
Verzenios®
Intervention Description
Oral 150 mg BID continuous
Primary Outcome Measure Information:
Title
Progression-free survival (PFS) within 24 weeks
Description
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.
Secondary Outcome Measure Information:
Title
Patients' quality of life by the Quality of life questionnaire - Core 30 (QLQ-C30)
Description
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
Title
Patients' quality of life by the Quality of Life Questionnaire - Breast cancer module (QLQ-BR23)
Description
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
Title
Patients' quality of life by the Quality of Life G8
Description
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
Title
Objective response rate (ORR)
Description
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
Title
Duration of response (DoR)
Description
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
Title
Progression-free-survival 1 (PFS1)
Description
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
Title
Progression-free-survival 2 (PFS2)
Description
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
Title
PFS1 and PFS2 in prespecified subgroups defined by stratification factors
Description
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
Time Frame
Throughout the study up to 48 months
Title
Overall survival (OS)
Description
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
Title
Incidence of Treatment-Emergent Adverse Events
Description
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
Title
Maintenance regimens after chemotherapy regimen
Description
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
Title
Circulating tumor cell (CTC) count
Description
To study the predictive and prognostic value of circulating tumor cell count (<5 versus ≥ 5 CTC/7.5mL)
Time Frame
At baseline

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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-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. 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cécile VISSAC SABATIER
Phone
0625155960
Email
c-vissac@unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Véronique DIERAS, Dr
Organizational Affiliation
Centre Eugène Marquis, Rennes
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gilles FREYER, Pr
Organizational Affiliation
Centre Hospitalier Lyon Sud
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre Benite
ZIP/Postal Code
69495
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gilles Freyer, MD
Phone
33-478-864-318
Email
gilles.freyer@chu-lyon.fr
Facility Name
Centre Eugène Marquis
City
Rennes
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Véronique DIERAS

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing 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.
IPD Sharing 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.

Learn more about this trial

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

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