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

NCT05128773 | Terminated Phase 3 Results DMC FDA Drug

• 6 other identifiers: EFC16133U1111-1244-1767BIG 20-01AFT-55EORTC-20332021-000398-10
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 2

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Invasive Breast Cancer-free Survival (IBCFS)

  IBCFS was defined according to standardized definitions for efficacy outcome measure in adjuvant breast cancer trials (STEEP) criteria version 2.0 as the time interval from the date of randomization to the date of the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence (IIBTR): invasive breast cancer involving the same breast parenchyma as the original primary; local-regional invasive breast cancer recurrence: invasive breast cancer in the axilla, regional lymph nodes, chest wall, and skin of the ipsilateral breast; distant recurrence: metastatic disease-breast cancer that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer, invasive contralateral breast cancer; death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause.

  From randomization to the date of first occurrence of IBCFS event (maximum exposure duration: 155 days)

Secondary Outcomes (9)

• Invasive Disease-Free Survival (IDFS)

  From randomization to the date of first occurrence of IDFS event (maximum exposure duration: 155 days)

• Distant Recurrence-free Survival (DRFS)

  From randomization to the date of the first occurrence of distant recurrence or death due to any cause, whichever occurs first (maximum exposure duration: 155 days)

• Locoregional Recurrences-free Survival (LRRFS)

  From randomization to the date of the first occurrence of local/regional ipsilateral recurrence or breast cancer or death due to any cause, whichever occurs first (maximum exposure duration: 155 days)

• Overall Survival (OS)

  From randomization to the date of death due to any cause (maximum exposure duration: 155 days)

• Breast Cancer-specific Survival (BCSS)

  From randomization to the date of death due to breast cancer (maximum exposure duration: 155 days)

Study Arms (2)

Amcenestrant with tamoxifen-matching placebo arm

EXPERIMENTAL

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

Drug: Amcenestrant; Drug: Tamoxifen-matching placebo

Tamoxifen with amcenestrant-matching placebo

ACTIVE COMPARATOR

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

Drug: Tamoxifen; Drug: Amcenestrant-matching placebo

Interventions

Amcenestrant DRUG

tablet, oral

Amcenestrant with tamoxifen-matching placebo arm

Tamoxifen DRUG

tablet, oral

Tamoxifen with amcenestrant-matching placebo

Amcenestrant-matching placebo DRUG

tablet, oral

Tamoxifen with amcenestrant-matching placebo

Tamoxifen-matching placebo DRUG

tablet, oral

Amcenestrant with tamoxifen-matching placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Breast International Group: collaborator
• Alliance Foundation Trials, LLC.: collaborator
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator

Study Sites (2)

Investigational Site Number :1521622

Santiago, Reg Metropolitana de Santiago, Chile

Location

Investigational Site Number :1561599

Haikou, 570311, China

Location

Related Links

• EFC16133 Plain Language Results Summary

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Due to premature discontinuation and closure of study decided by the Sponsor, only safety data were summarized and reported, and no efficacy data was collected.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Etienne Brain, MD PhD

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

  STUDY CHAIR

• David Cameron, Professor of Oncology

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

  STUDY CHAIR

• Otto Metzger, MD

  Dana-Farber Cancer Institute, 450 Brookline Avenue Yawkey 1250

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-dummy
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2021
• First Posted: November 22, 2021
• Study Start: February 17, 2022
• Primary Completion: October 13, 2022
• Study Completion: October 13, 2022
• Last Updated: September 16, 2025
• Results First Posted: June 22, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

CN (1); CL (1)