Phase 2 Study of SAR439859 Versus Physician's Choice in Locally Advanced or Metastatic ER-positive Breast Cancer (AMEERA-3)
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| ClinicalTrials.gov Identifier: NCT04059484 |
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Recruitment Status :
Recruiting
First Posted : August 16, 2019
Last Update Posted : January 6, 2021
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Sponsor:
Sanofi
Information provided by (Responsible Party):
Sanofi
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Brief Summary:
Primary Objective:
To determine whether SAR439859 per os improves progression free survival (PFS) when compared with a endocrine monotherapy of the choice of the physician, in participants with metastatic or locally advanced breast cancer.
Secondary Objectives:
- To compare the overall survival in the 2 treatment arms
- To assess the objective response rate in the 2 treatment arms.
- To evaluate the disease control rate in the 2 treatment arms.
- To evaluate the clinical benefit rate in the 2 treatment arms.
- To evaluate the duration of response in the 2 treatment arms.
- To evaluate the PFS according to the estrogen receptor 1 gene (ESR1) mutation status in the 2 treatment arms.
- To evaluate the pharmacokinetics of SAR439859 as single agent.
- To evaluate health related quality of life in the 2 treatment arms.
- To compare the overall safety profile in the 2 treatment arms.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Breast Cancer Metastatic | Drug: SAR439859 Drug: Fulvestrant Drug: Anastrozole Drug: Letrozole Drug: Exemestane Drug: Tamoxifen | Phase 2 |
The duration of the study for an individual participant will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of at least 1 cycle (28 days of study treatment), and an end of treatment (EOT) visit at least 30 days (or until the participant receive another anticancer therapy, whichever is earlier) following the last administration of study treatment. Study treatment may continue until precluded by unacceptable toxicity, disease progression, death or upon participant's request.
An extension of recruitment for Chinese participants is planned in this study: After completion of randomization in the global part of the study, randomization will continue in China until approximately 90 Chinese participants are randomized.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 372 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Single (Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | An Open Label Randomized Phase 2 Trial of SAR439859, Versus Endocrine Monotherapy as Per Physician's Choice in Patients With Estrogen Receptor-positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer With Prior Exposure to Hormonal Therapies (AMEERA-3) |
| Actual Study Start Date : | October 22, 2019 |
| Estimated Primary Completion Date : | July 2023 |
| Estimated Study Completion Date : | July 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: SAR439859
Daily SAR439859 dose administered orally under fed or fast condition
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Drug: SAR439859
Pharmaceutical form: Capsule Route of administration: Oral |
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Active Comparator: Fulvestrant/Aromatase inhibitors/Estrogen receptor modulator
Control treatment of the choice of the physician depending on each participant's medical condition and in accordance with the approved label may include 1 of the following treatments used as monotherapy. Fulvestrant Aromatase inhibitors (anastrozole, letrozole, exemestane) Selective estrogen receptor modulator (Tamoxifen) |
Drug: Fulvestrant
Pharmaceutical form: Solution for injection Route of administration: Intramuscular Other Name: Faslodex® Drug: Anastrozole Pharmaceutical form:Tablets or capsules Route of administration: Oral Other Name: Arimidex®/Anastrozole Generics Drug: Letrozole Pharmaceutical form: Tablets or capsules Route of administration: Oral Other Name: Femara®/Letrozole Generics Drug: Exemestane Pharmaceutical form: Tablets or capsules Route of administration: Oral Other Name: Aromasin®/Exemestane Generics Drug: Tamoxifen Pharmaceutical form: Tablets or capsules Route of administration: Oral Other Name: Nolvadex®/Tamoxifen Generics |
Primary Outcome Measures :
- Progression free survival (PFS) [ Time Frame: Up to 18 months after the first randomized participant ]PFS is defined as the time interval from the date of randomization to the date of documented tumor progression as per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or death (due to any cause), whichever comes first.
Secondary Outcome Measures :
- Overall Survival (OS) [ Time Frame: Up to 64 months after the first randomized participant ]OS is defined as the time interval from the date of randomization to the date of documented death (due to any cause).
- Objective Response Rate (ORR) [ Time Frame: Up to 18 months after the first randomized participant ]ORR is defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR), as best overall response determined by RECIST 1.1 from the date of randomization to the date of end of treatment.
- Disease Control Rate (DCR) [ Time Frame: Up to 18 months after the first randomized participant ]DCR is defined as the proportion of participants who have a confirmed CR, PR, or stable disease (SD) determined by RECIST 1.1 from the date of randomization to the date of end of treatment.
- Clinical Benefit Rate (CBR) [ Time Frame: Up to 18 months after the first randomized participant ]CBR is defined as the proportion of participants who have a confirmed CR, PR, or stable disease (SD) for at least 24 weeks determined by RECIST 1.1 from the date of randomization to the date of end of treatment.
- Duration of Response (DOR) [ Time Frame: Up to 18 months after the first randomized participant ]DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) as determined by objective radiographic disease assessment per RECIST 1.1 or death from any cause, whichever occurs first.
- PFS according to (ESR1) mutation status [ Time Frame: Up to 18 months after the first randomized participant ]PFS as per the estrogen receptor 1 (ESR1) mutation status determined at study entry.
- Assessments of the Pharmacokinetic (PK) parameter of SAR439859 as single agent: Plasma Concentrations [ Time Frame: Day 1 and Day 15 of Cycle 1 and Day 1 of cycles 3, 4 and 6 (each cycle is 28 days) ]SAR439859 plasma concentrations.
- Patient Reported Outcome (PRO) - health-related quality of life and health status using the European Quality of Life-5 Dimensions (EQ-5D) [ Time Frame: Day 1 of Cycle 1 and day 1 of subsequent cycle every 2 cycles up to 30 days after last study treatment (each cycle is 28 days) ]EQ-5D is a standardized measure of health status.
- Patient Reported Outcome (PRO) - the European Organisation for Research and Treatment of Cancer core quality of life questionnaire (EORTC-QLQ-C30) [ Time Frame: Day 1 of Cycle 1 and day 1 of subsequent cycle every 2 cycles up to 30 days after last study treatment (each cycle is 28 days) ]The EORTC-QLQ-C30 is composed of both multi item scales and single item measures. These include 5 functional scales, 3 symptom scales, a Global Health Status (GHS)/quality of life scale, and 6 single items.
- Patient Reported Outcome (PRO) - EORTC-QLQ breast cancer (EORTC-QLQ-BR23) [ Time Frame: Day 1 of Cycle 1 and day 1 of subsequent cycle every 2 cycles up to 30 days after last study treatment (each cycle is 28 days) ]The EORTC-QLQ-BR23 contains 23 items: 8 assessing function and 15 items assessing symptoms of disease or treatment.
- Overall safety profile - Treatment-Emergent Adverse events [ Time Frame: Evaluated continuously throughout study from the date of enrollment, up to 30 days after last study treatment administration ]Number of participants with treatment-emergent adverse events (TEAEs).
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion criteria :
- 18 years or older.
- Histological or cytological diagnosis of adenocarcinoma of the breast.
- Locally advanced not amenable to radiation therapy or surgery in a curative intent, and/or metastatic disease.
- ER positive status.
- HER2 negative status.
- Participants must have received no more than 1 prior chemotherapeutic or 1 targeted therapy regimen for advanced/metastatic disease.
- In the main study, a prior treatment with a CDK 4/6 inhibitor is mandatory if this treatment is approved and can be reimbursed for this participant. The percentage of participants without previous CDK 4/6 inhibitor will be capped to 20%. In the Chinese extension cohort, previous treatment with a CDK 4/6 inhibitor will not be mandatory, and there will be no limitation to the number of participants naïve to CDK4/6 inhibitor.
- Participants must present a secondary endocrine resistance to endocrine therapy defined as: progression while on endocrine therapy after at least 6 months of treatment for advanced breast cancer, or relapse while on adjuvant endocrine therapy but after the first 2 years, or with a relapse within 12 months after completing adjuvant endocrine therapy.
- Male or Female.
Exclusion criteria:
- Eastern Cooperative Oncology Group performance status ≥2.
- Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of SAR439859. Participants unable to swallow normally and to take capsules.
- Participant with any other cancer. Adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or any other cancer from which the participant has been disease free for >3 years are allowed.
- Severe uncontrolled systemic disease at screening.
- Participants with known brain metastases that are untreated, symptomatic or require therapy to control symptoms.
- Prior treatment with mammalian target of rapamycin inhibitors or any other selective estrogen receptor degrader (SERD) compound, except fulvestrant if stopped for at least3 months before randomization.
- Treatment with drugs that have the potential to inhibit UGT less than 2 weeks before randomization .
- Treatment with strong or moderate CYP3A/CYP2C8 inducers within 2 weeks before randomization.
- Ongoing treatment with drugs that are substrate of P-glycoprotein (P gp) (dabigatran, digoxin, fexofenadine).
- Treatment with anticancer agents (including investigational drugs) less than 3 weeks before randomization.
- Inadequate hematological, coagulation, renal and liver functions.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Information from the National Library of Medicine
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): NCT04059484
Contacts
| Contact: Trial Transparency email recommended (Toll free number for US & Canada) | 800-633-1610 ext 1 then # | Contact-US@sanofi.com |
Locations
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Sponsors and Collaborators
Sanofi
Investigators
| Study Director: | Clinical Sciences & Operations | Sanofi |
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT04059484 |
| Other Study ID Numbers: |
ACT16105 2018-004593-98 ( EudraCT Number ) |
| First Posted: | August 16, 2019 Key Record Dates |
| Last Update Posted: | January 6, 2021 |
| Last Verified: | January 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Tamoxifen Letrozole Fulvestrant Anastrozole Exemestane Antineoplastic Agents Aromatase Inhibitors |
Steroid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Estrogen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents, Hormonal Selective Estrogen Receptor Modulators Estrogen Receptor Modulators Bone Density Conservation Agents Estrogen Receptor Antagonists |