Study of Amcenestrant (SAR439859) Versus Tamoxifen for Patients With Hormone Receptor-positive (HR+) Early Breast Cancer, Who Have Discontinued Adjuvant Aromatase Inhibitor Therapy Due to Treatment-related Toxicity

NCT ID: NCT05128773

Last Updated: 2025-09-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-17
• Study Completion Date: 2022-10-13

Brief Summary

This was a phase III, randomized, double blind, multicenter, 2-arm study evaluating the efficacy and safety of amcenestrant compared with tamoxifen in participants with hormone receptor-positive early breast cancer who discontinued adjuvant aromatase inhibitor (AI) therapy due to treatment related toxicity. The primary objective was to demonstrate the superiority of amcenestrant versus tamoxifen on invasive breast cancer-free survival.

The treatment duration per participant was to be 5 years, followed with a subsequent 5-years follow-up period. For the treatment period, visits were scheduled at the start of treatment, then at 4 weeks and 12 weeks after treatment start, and then every 12 weeks for the first 2 years and every 24 weeks for year 3 to 5. For the follow-up period, visits were scheduled 30 days after last treatment and then every 12 months. Three periods were planned:

• A screening period of up to 28 days,
• A treatment period of up to 5 years,
• A follow-up period of up to 5 years.

Detailed Description

Study duration per participant was to be approximately 10 years.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Amcenestrant with tamoxifen-matching placebo arm

Amcenestrant dose, once daily, continuously. Tamoxifen-matching placebo, once daily, continuously.

Group Type: EXPERIMENTAL

Amcenestrant

Intervention Type: DRUG

tablet, oral

Tamoxifen-matching placebo

Intervention Type: DRUG

tablet, oral

Tamoxifen with amcenestrant-matching placebo

Tamoxifen dose, once daily, continuously. Amcenestrant-matching placebo, once daily, continuously.

Group Type: ACTIVE_COMPARATOR

Tamoxifen

Intervention Type: DRUG

tablet, oral

Amcenestrant-matching placebo

Intervention Type: DRUG

tablet, oral

Interventions

Amcenestrant

tablet, oral

Intervention Type: DRUG

Tamoxifen

tablet, oral

Intervention Type: DRUG

Amcenestrant-matching placebo

tablet, oral

Intervention Type: DRUG

Tamoxifen-matching placebo

tablet, oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult participants with histologically confirmed diagnosis of adenocarcinoma of the breast with documentation of hormone receptor-positive status, irrespective of human epidermal growth factor receptor 2 (HER2) status NOTE: Participants with HER2-positive breast cancer were eligible only if they had completed their adjuvant anti-HER2 treatment and chemotherapy.
• With Stage IIB or Stage III (invasive breast cancer) who had undergone breast surgery and adjuvant radiation (if indicated) for the current malignancy.
• Who had received prior aromatase inhibitors (AIs) (letrozole, anastrozole or exemestane or any sequence thereof) per the following:

Adjuvant AI therapy was discontinued due to AI treatment-related toxicity; Minimum of 6 months duration and maximum of 30 months duration (from initiation of first AI if there was a switch between AIs) of AI therapy was required.

• Absence of locoregional and/or advanced/metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Capable of giving signed informed consent.

Exclusion Criteria

• Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of amcenestrant and/or tamoxifen. Participants unable to swallow normally or unable to take tablets and capsules. Predictable poor compliance to oral treatment. Active inflammatory bowel disease or chronic diarrhea, active hepatitis A/B/C, hepatic cirrhosis, short bowel syndrome, or any upper gastrointestinal surgery including gastric resection or banding procedures.
• History of prior breast cancer treated with AI.
• Any other solid tumor or lymphoma diagnosis was not allowed except if the participant had been free from disease for equal to greater than (=>5) years.
• Pregnant or nursing women, or women of child-bearing potential without a negative pregnancy test prior to randomization.
• Participants with unrecovered acute toxic effects of prior AI therapy or surgical procedures.
• Uncontrolled intercurrent illness, including psychiatric conditions that would have limited compliance with study requirements.
• Treatment with any selective estrogen receptor degrader (SERD), tamoxifen or toremifene were not allowed as prior adjuvant therapy but could have been used as neoadjuvant therapy for a total duration of 3 months. Participants who were treated with a SERD, tamoxifen or toremifene in the neoadjuvant setting and who experienced disease progression were not allowed. Prior treatment with raloxifene or tamoxifen for bone health, risk reduction, or a prior breast cancer was allowed provided this was discontinued at least 3 years before diagnosis of current breast cancer.
• Ongoing treatment with HER2 directed therapy. Appropriate wash out between the last dose of HER2 directed therapy and randomization should have been at least 4 weeks.

The above information was not intended to contain all considerations relevant to a potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Breast International Group

OTHER

Sponsor Role: collaborator

Alliance Foundation Trials, LLC.

OTHER

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Etienne Brain, MD PhD

Role: STUDY_CHAIR

Institut Curie (Saint-Cloud and Paris), 35 rue Dailly, 92210 Saint-Cloud

David Cameron, Professor of Oncology

Role: STUDY_CHAIR

University of Edinburgh Cancer Centre, institute of Genetics and Cancer, Western General Hospital, Crewe Road South, EDINBURGH EH4 2XU Scotland

Otto Metzger, MD

Role: STUDY_CHAIR

Dana-Farber Cancer Institute, 450 Brookline Avenue Yawkey 1250

Locations

Investigational Site Number :1521622

Santiago, Reg Metropolitana de Santiago, Chile

Investigational Site Number :1561599

Haikou, , China

Countries

Chile; China

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.trialsummaries.com/Study/StudyDetails?id=25240&tenant=MT_SNY_9011

EFC16133 Plain Language Results Summary

Other Identifiers

U1111-1244-1767

Identifier Type: REGISTRY

Identifier Source: secondary_id

BIG 20-01

Identifier Type: OTHER

Identifier Source: secondary_id

AFT-55

Identifier Type: OTHER

Identifier Source: secondary_id

EORTC-2033

Identifier Type: OTHER

Identifier Source: secondary_id

2021-000398-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC16133

Identifier Type: -

Identifier Source: org_study_id