Clinical Trials List
Protocol NumberEFC15935
NCT Number(ClinicalTrials.gov Identfier)NCT04478266
2021-02-08 - 2023-07-20
Phase III
Not yet recruiting1
Recruiting6
ICD-10C50.919
Malignant neoplasm of unspecified site of unspecified female breast
ICD-9174.9
Malignant neoplasm of female breast, unspecified
A randomized, multicenter, double-blind phase 3 study of SAR439859 plus palbociclib versus letrozole plus palbociclib for the treatment of patients with ER (+), HER2 (-) breast cancer who have not received prior systemic anti-cancer treatment for advanced disease
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Trial Applicant
-
Sponsor
Sanofi
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Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Wen-Ling Kuo 無
- Chan-Keng Yang 無
- Chia-Hui Chu 無
- Mengting Peng 無
- 周旭桓 無
- Chi-Chang Yu 無
- Wen-Chi Shen 無
- 沈士哲 無
- Yung-Chang Lin 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 馮晉榮 無
- 林燕淑 無
- 賴亦貞 無
- 邱仁輝 無
- Chi-Cheng Huang 無
- Ta-Chung Chao 無
- Jiun-I Lai 無
- Chun-Yu Liu 無
- Yi-Fang Tsai 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林柏翰 Division of Hematology & Oncology
- 羅喬 Division of Hematology & Oncology
- 林季宏 Division of Hematology & Oncology
- 陳怡君 未分科
- Wei-Wu Chen Division of Hematology & Oncology
- MING-YANG WANG Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- WEI-LI MA Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Jui-Hung Tsai Division of Hematology & Oncology
- Yao-Lung Kuo Division of General Surgery
- Chun-Hui Lee Division of Hematology & Oncology
- Kuo-Ting Lee Division of General Surgery
- 楊舜如 Division of Hematology & Oncology
- Zhu-Jun Loh Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Fang-Ming Chen Division of General Surgery
- 巫承哲 Division of General Surgery
- 甘蓉瑜 Division of General Surgery
- Chung-Liang Li 無
- Chieh-Han Chuang Division of General Surgery
- Shen Liang Shih Division of General Surgery
- 高捷妮 Division of General Surgery
- Fu Ouyang Division of General Surgery
- Junping Shiau Shiau 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
ER (+), HER2 (-) breast cancer
Objectives
Primary Objective:
To determine whether Amcenestrant (SAR439859) in combination with palbociclib improvesprogression free survival (PFS) when compared with letrozole in combination with palbociclib in participants with ER+, HER2- advanced breast cancer who have not received any prior systemic anticancer therapies for advanced disease.
Secondary Objective:
To compare the overall survival in both treatment arms
To evaluate the objective response rate in both treatment arms
To evaluate the duration of response in both treatment arms
To evaluate the clinical benefit rate in both treatment arms
To evaluate progression-free survival on next line of therapy
To evaluate the pharmacokinetics of amcenestrant, and palbociclib
To evaluate health-related quality of life in both treatment arms
To evaluate the time to first chemotherapy in both treatment arms
To evaluate safety in both treatment arms
Test Drug
SAR439859
Active Ingredient
SAR439859
Dosage Form
tablet
Dosage
200
Endpoints
Primary Outcome Measures :
Progression-free survival [ Time Frame: From randomization date to date of first documentation of progression OR death (up to approximately 4 years) ]
Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death (due to any cause), whichever come first.
Progression-free survival [ Time Frame: From randomization date to date of first documentation of progression OR death (up to approximately 4 years) ]
Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death (due to any cause), whichever come first.
Inclution Criteria
INCLUSION CRITERIA
Participants are eligibleto be included in the study only if all of the following criteria apply:
Age
I 01.Participant must be 18 years of age (inclusive) or older, or country's legal age of majority if the legal adult age is >18 years old at the time of signing the informed consent.Type of participant and disease characteristics
I 02.Participants with histological or cytological proven diagnosis of adenocarcinoma of the breast with evidence of either loco-regional recurrent or metastatic disease not amenable to radiation therapy or surgery in a curative intent, and for whom chemotherapy is not indicated.
I 03.Documentation of ER-positive (≥1% positive stained cells) based on most recent tumor cell staining by immunohistochemistry (IHC) assay consistent with local standards. -Note that if the primary tumor is ER-positive and any further metastatic lesion is ER-negative, the participant cannot be selected for inclusion
I 04.Documentation on the most recently analyzed biopsy (either primary tumor or any metastatic site) of HER2 non over-expressing by IHC (0, 1+), or in situ hybridization-negative based on single-probe average HER2 copy number <6.0 signals/cell or dual-probe HER2/centromeric probe for chromosome 17 (CEP17) ratio <2 with an average HER2 copy number <6.0 signals/cell as per American Society of Clinical Oncology guidelines(38).-Note that if the primary tumor is HER2-negative and any further metastatic lesion is HER2-positive, the participant cannot be selected for inclusion.
I 05.Participants previously untreated with any systemic anti-cancer therapy for their loco-regional recurrent or metastatic disease.
I 06.Measurable or non-measurable disease evaluable per RECIST v.1.1. For bone-only metastases, at least one predominant lytic bone lesion or mixed lytic-blastic lesion must be present.Tumor lesions previously irradiated or subjected to other loco-regional therapy will only be deemed measurable if disease progression at the treated site after completion of therapy is clearly documented.
I 07.Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2(criterion modified by amendment 02).
I 08.Willingness and ability to provide tumor tissues [ie,archived formalin fixed paraffin embedded (FFPE) tissues]. If tumor tissue is notavailable, then a fresh biopsy will be required for patient participation.
Sex
I 09.Male,or Femaleof any menopausal status (pre-, peri-or post-menopausal) are eligible. Post-menopausal status is defined inSection10.4(Appendix 4). Pre/peri-menopausal women are those not meeting the criteria for being post-menopausal.
nformed Consent
I 10.Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Participants are eligibleto be included in the study only if all of the following criteria apply:
Age
I 01.Participant must be 18 years of age (inclusive) or older, or country's legal age of majority if the legal adult age is >18 years old at the time of signing the informed consent.Type of participant and disease characteristics
I 02.Participants with histological or cytological proven diagnosis of adenocarcinoma of the breast with evidence of either loco-regional recurrent or metastatic disease not amenable to radiation therapy or surgery in a curative intent, and for whom chemotherapy is not indicated.
I 03.Documentation of ER-positive (≥1% positive stained cells) based on most recent tumor cell staining by immunohistochemistry (IHC) assay consistent with local standards. -Note that if the primary tumor is ER-positive and any further metastatic lesion is ER-negative, the participant cannot be selected for inclusion
I 04.Documentation on the most recently analyzed biopsy (either primary tumor or any metastatic site) of HER2 non over-expressing by IHC (0, 1+), or in situ hybridization-negative based on single-probe average HER2 copy number <6.0 signals/cell or dual-probe HER2/centromeric probe for chromosome 17 (CEP17) ratio <2 with an average HER2 copy number <6.0 signals/cell as per American Society of Clinical Oncology guidelines(38).-Note that if the primary tumor is HER2-negative and any further metastatic lesion is HER2-positive, the participant cannot be selected for inclusion.
I 05.Participants previously untreated with any systemic anti-cancer therapy for their loco-regional recurrent or metastatic disease.
I 06.Measurable or non-measurable disease evaluable per RECIST v.1.1. For bone-only metastases, at least one predominant lytic bone lesion or mixed lytic-blastic lesion must be present.Tumor lesions previously irradiated or subjected to other loco-regional therapy will only be deemed measurable if disease progression at the treated site after completion of therapy is clearly documented.
I 07.Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2(criterion modified by amendment 02).
I 08.Willingness and ability to provide tumor tissues [ie,archived formalin fixed paraffin embedded (FFPE) tissues]. If tumor tissue is notavailable, then a fresh biopsy will be required for patient participation.
Sex
I 09.Male,or Femaleof any menopausal status (pre-, peri-or post-menopausal) are eligible. Post-menopausal status is defined inSection10.4(Appendix 4). Pre/peri-menopausal women are those not meeting the criteria for being post-menopausal.
nformed Consent
I 10.Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria
EXCLUSION CRITERIA
Participantsare excluded from the study if any of the following criteria apply:
Medical conditions
E 01.Participants with known active brain metastases(criterion modified by amendment 02).Participants with treated/stable brain metastases are eligible if they:-Have completed treatment (whole brain radiotherapy, radiosurgery, or combination)/stable brain metastases for at least 4 weeks prior to start of study treatment, and-Have recovered from the effects of this treatment, and-Are neurologically stable-If receiving corticosteroid for central nervous system adverse events, the dose should be stable or decreasing over≥2 weeks prior to first IMP.
E 02.Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of SAR439859 and/or palbociclib. Participants unableto swallow normally and to take capsules or tablets. Predictable poor compliance to oral treatment. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or total gastric resection.
E 03.Diagnosis of any other malignancy within 3 years prior to randomization. Adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer are allowed.
E 04.Pregnant or nursing woman, or woman who intends to become pregnant during the study. Woman of childbearing potential (WOCBP) unwilling to prevent pregnancy using highly effective non-hormonal contraception during treatment, and for at least 12weeks after discontinuation of any study intervention and/or WOCBP unwilling to be tested for pregnancy before study treatment, every 28 days during treatment, and for at least 12weeks after the last dose of any study intervention.Note: WOCBP is a woman who is considered fertile following menarche and until becoming post-menopausal, unless permanently sterile.
E 05.Male participants who disagree to practice true abstinence or disagree to use a condom during sexual contact with a pregnant woman or a WOCBP while participating in the study, and for at least 14 weeks after the last dose of any study intervention.Note: True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, and post-ovulation methods) and withdrawal are not acceptable methods of contraception.
E 06.Participants with unrecovered acute toxic effects of prior anti-cancer therapy or surgical procedures of NCI CTCAE version 5.0 Grade >1 (except alopecia or other toxicities not considered a safety risk for the participant at investigator's discretion, eg,3-month stable Grade 2 peripheral neuropathy), or with Pneumonitis, and Interstitial Lung Disease (ILD).
E 07.Participants with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term (including participants with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, leptomeningeal carcinomatosis, and over 50% liver involvement).
E 08.Significant concomitant illness, including psychiatric condition that, in the opinion of the Investigator or Sponsor, would adverselyaffect the participant’s participation in the study.
E 09.Participants with abnormal coagulation profiles, or any history of coagulopathy within 6 months prior to the first dose of IMP, including history of deep vein thrombosis (DVT) or pulmonary embolism. However, participants (except pre/perimenopausal women and male participants) with adequately treated catheter-related venous thrombosis occurring more than one month prior to the first dose of IMP will be allowed to participate (criterion modified by amendment 02).
E 10.Prothrombin time/international normalized ratio (INR) >1.5 times the upper limit of normal (ULN) or outside therapeutic range if receiving anticoagulation that would affect the prothrombin time/INR. However, participants (except pre/perimenopausalwomen and male participants) being treated with an anticoagulant for a stable and allowed medical condition (eg, well controlled atrial fibrillation), provided dose and coagulation parameters (as defined by local standard of care) are stable for at least one month prior to the first dose of study drug will be allowed to participate.
Prior/concomitant therapy
E 11.Ongoing treatment with drugs that are sensitive substrates of P-glycoprotein (P-gp) (dabigatran, digoxin, fexofenadine) or BCRP (rosuvastatin, sulfasalazine).
E 12.Treatment with strong CYP3A inhibitors and strong or moderate CYP3A inducers within 2weeks before first study treatment administration or 5 elimination half-lives whichever is longest and cannot be replaced.
E 13.Treatment with strong or moderate CYP2C8 inducers within 2 weeks before first study treatment administration or 5 elimination half-lives whichever is longest and cannot be replaced.
E 14.Treatment with drugs that have the potential to inhibit UGT, including, but not limited, to atazanavir and probenecid, within 2 weeks before study treatment administration or 5elimination half-lives whichever is longest and which cannot be replaced.
E 15.Medical conditions requiring concomitant administration of medications with a narrow therapeutic window metabolized by CYP3A and for which a dose reduction cannot be considered.
E 16.Disease recurrence while on, or within 12 months of completion of (neo)adjuvant aromatase inhibitor-containing therapy (eg,letrozole, anastrozole, exemestaneas monotherapy, or in combination with targeted therapy).
E 17.Prior (neo)adjuvant treatment with another selective ER down-regulator (SERD).
E 18.Major surgery or radiotherapy within 4 weeks before randomization. Participants who received prior radiotherapy to ≥25% of bone marrow are not eligible independent of when it was received.
E 19.Drugs that are known to prolong the QT interval (premenopausaland maleparticipants)
Prior/concurrent clinical study experience
E 20.Participation within 4 weeks before randomization in any other clinical study involving an investigational study treatment including anti-cancer agents or within 2weeks before randomization for any other type of medical research.
Diagnostic assessments
E 21.Inadequate hematological function including:
-Neutrophils <1.5 ×109/L
-Platelet count <100 ×109/L
E 22.Inadequate renal function estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² as estimated using the abbreviated Modification of Diet in Renal Disease formula (seeSection10.12).
E 23.Inadequate liver function defined as:
-Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 × ULN (>5.0 ×ULN if liver metastases present)
-Alkaline phosphatase (ALP) > 2.5 ×ULN (>5.0 ×ULN if bone or liver metastases present)
-Total bilirubin >1.5 × ULN (>3.0 ×ULN if Gilbert’s disease).
E 24.Known hypersensitivity/contraindicated to goserelin (men and pre/perimenopausal participants), palbociclib, letrozole, or any of their excipients, or to any SAR439859 and placebo excipients.
E 25.Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
E 26.Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk ofnoncompliance to study procedures.
E 27.Participants are dependent on the Sponsor or Investigator (in conjunction with Section 1.61 of the ICH-GCPOrdinance E6).
E 28.Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals.
E 29.Any country-related specific regulation that would prevent the participant from entering the study -see Appendix 6(Section10.6) (country specific requirements).
Participantsare excluded from the study if any of the following criteria apply:
Medical conditions
E 01.Participants with known active brain metastases(criterion modified by amendment 02).Participants with treated/stable brain metastases are eligible if they:-Have completed treatment (whole brain radiotherapy, radiosurgery, or combination)/stable brain metastases for at least 4 weeks prior to start of study treatment, and-Have recovered from the effects of this treatment, and-Are neurologically stable-If receiving corticosteroid for central nervous system adverse events, the dose should be stable or decreasing over≥2 weeks prior to first IMP.
E 02.Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of SAR439859 and/or palbociclib. Participants unableto swallow normally and to take capsules or tablets. Predictable poor compliance to oral treatment. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or total gastric resection.
E 03.Diagnosis of any other malignancy within 3 years prior to randomization. Adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer are allowed.
E 04.Pregnant or nursing woman, or woman who intends to become pregnant during the study. Woman of childbearing potential (WOCBP) unwilling to prevent pregnancy using highly effective non-hormonal contraception during treatment, and for at least 12weeks after discontinuation of any study intervention and/or WOCBP unwilling to be tested for pregnancy before study treatment, every 28 days during treatment, and for at least 12weeks after the last dose of any study intervention.Note: WOCBP is a woman who is considered fertile following menarche and until becoming post-menopausal, unless permanently sterile.
E 05.Male participants who disagree to practice true abstinence or disagree to use a condom during sexual contact with a pregnant woman or a WOCBP while participating in the study, and for at least 14 weeks after the last dose of any study intervention.Note: True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, and post-ovulation methods) and withdrawal are not acceptable methods of contraception.
E 06.Participants with unrecovered acute toxic effects of prior anti-cancer therapy or surgical procedures of NCI CTCAE version 5.0 Grade >1 (except alopecia or other toxicities not considered a safety risk for the participant at investigator's discretion, eg,3-month stable Grade 2 peripheral neuropathy), or with Pneumonitis, and Interstitial Lung Disease (ILD).
E 07.Participants with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term (including participants with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, leptomeningeal carcinomatosis, and over 50% liver involvement).
E 08.Significant concomitant illness, including psychiatric condition that, in the opinion of the Investigator or Sponsor, would adverselyaffect the participant’s participation in the study.
E 09.Participants with abnormal coagulation profiles, or any history of coagulopathy within 6 months prior to the first dose of IMP, including history of deep vein thrombosis (DVT) or pulmonary embolism. However, participants (except pre/perimenopausal women and male participants) with adequately treated catheter-related venous thrombosis occurring more than one month prior to the first dose of IMP will be allowed to participate (criterion modified by amendment 02).
E 10.Prothrombin time/international normalized ratio (INR) >1.5 times the upper limit of normal (ULN) or outside therapeutic range if receiving anticoagulation that would affect the prothrombin time/INR. However, participants (except pre/perimenopausalwomen and male participants) being treated with an anticoagulant for a stable and allowed medical condition (eg, well controlled atrial fibrillation), provided dose and coagulation parameters (as defined by local standard of care) are stable for at least one month prior to the first dose of study drug will be allowed to participate.
Prior/concomitant therapy
E 11.Ongoing treatment with drugs that are sensitive substrates of P-glycoprotein (P-gp) (dabigatran, digoxin, fexofenadine) or BCRP (rosuvastatin, sulfasalazine).
E 12.Treatment with strong CYP3A inhibitors and strong or moderate CYP3A inducers within 2weeks before first study treatment administration or 5 elimination half-lives whichever is longest and cannot be replaced.
E 13.Treatment with strong or moderate CYP2C8 inducers within 2 weeks before first study treatment administration or 5 elimination half-lives whichever is longest and cannot be replaced.
E 14.Treatment with drugs that have the potential to inhibit UGT, including, but not limited, to atazanavir and probenecid, within 2 weeks before study treatment administration or 5elimination half-lives whichever is longest and which cannot be replaced.
E 15.Medical conditions requiring concomitant administration of medications with a narrow therapeutic window metabolized by CYP3A and for which a dose reduction cannot be considered.
E 16.Disease recurrence while on, or within 12 months of completion of (neo)adjuvant aromatase inhibitor-containing therapy (eg,letrozole, anastrozole, exemestaneas monotherapy, or in combination with targeted therapy).
E 17.Prior (neo)adjuvant treatment with another selective ER down-regulator (SERD).
E 18.Major surgery or radiotherapy within 4 weeks before randomization. Participants who received prior radiotherapy to ≥25% of bone marrow are not eligible independent of when it was received.
E 19.Drugs that are known to prolong the QT interval (premenopausaland maleparticipants)
Prior/concurrent clinical study experience
E 20.Participation within 4 weeks before randomization in any other clinical study involving an investigational study treatment including anti-cancer agents or within 2weeks before randomization for any other type of medical research.
Diagnostic assessments
E 21.Inadequate hematological function including:
-Neutrophils <1.5 ×109/L
-Platelet count <100 ×109/L
E 22.Inadequate renal function estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² as estimated using the abbreviated Modification of Diet in Renal Disease formula (seeSection10.12).
E 23.Inadequate liver function defined as:
-Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 × ULN (>5.0 ×ULN if liver metastases present)
-Alkaline phosphatase (ALP) > 2.5 ×ULN (>5.0 ×ULN if bone or liver metastases present)
-Total bilirubin >1.5 × ULN (>3.0 ×ULN if Gilbert’s disease).
E 24.Known hypersensitivity/contraindicated to goserelin (men and pre/perimenopausal participants), palbociclib, letrozole, or any of their excipients, or to any SAR439859 and placebo excipients.
E 25.Individuals accommodated in an institution because of regulatory or legal order; prisoners or participants who are legally institutionalized.
E 26.Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk ofnoncompliance to study procedures.
E 27.Participants are dependent on the Sponsor or Investigator (in conjunction with Section 1.61 of the ICH-GCPOrdinance E6).
E 28.Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals.
E 29.Any country-related specific regulation that would prevent the participant from entering the study -see Appendix 6(Section10.6) (country specific requirements).
The Estimated Number of Participants
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Taiwan
11 participants
-
Global
708 participants
