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

JRCT ID: jRCT2031220056

Registered date:11/05/2022

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Breast cancer
• Date of first enrollment: 16/05/2022
• Target sample size: 3738
• Countries of recruitment: Chile,Japan,China,Japan
• Study type: Interventional

Intervention(s)

Drug: Amcenestrant (SAR439859)
Pharmaceutical form: Tablet, Route of administration: Oral
Drug: Amcenestrant-matching placebo
Pharmaceutical form: Tablet, Route of administration: Oral
Drug: Tamoxifen
Pharmaceutical form: Tablet, Route of administration: Oral
Drug: Tamoxifen-matching placebo
Pharmaceutical form: Tablet, Route of administration: Oral

Outcome(s)

Primary Outcome

1. Invasive breast cancer-free survival (IBCFS) [ Time Frame: From randomization up to approximately 10 years ]
IBCFS is defined 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), local-regional invasive breast cancer recurrence, distant recurrence, invasive contralateral breast cancer, death attributable to any cause

Secondary Outcome

1. Invasive disease-free survival (IDFS) [ Time Frame: From randomization up to approximately 10 years ]
IDFS is defined 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), local-regional invasive breast cancer recurrence, distant recurrence, invasive contralateral breast cancer, second nonbreast primary invasive cancer, death attributable to any cause
2. Distant recurrence-free survival (DRFS) [ Time Frame: From randomization up to approximately 10 years ]
DRFS is defined as the time interval from the date of randomization to the date of the first occurrence of one of the following events: distant recurrence or death attributable to any cause
3. Locoregional recurrences-free survival (LRRFS) [ Time Frame: From randomization up to approximately 10 years ]
LRRFS is defined as the time interval from the date of randomization to the date of the first occurrence of one of the following events: local/regional ipsilateral recurrence, invasive contralateral breast cancer or death attributable to any cause
4. Overall survival (OS) [ Time Frame: From randomization up to approximately 10 years ]
Overall survival is defined as the time interval from the date of randomization to the date of documented death (due to any cause)
5. Breast cancer-specific survival (BCSS) [ Time Frame: From randomization up to approximately 10 years ]
BCSS is defined as the time interval from the date of randomization to the date of documented death attributable to breast cancer cause
6. Patient-reported overall treatment-related side effect bother as measured by the Functional Assessment of Cancer Therapy Item GP-5 (FACT-GP5) [ Time Frame: From baseline up to 2 years after the end of treatment (up to approximately 7 years) ]
7. Patient-reported treatment-related symptoms as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Breast cancer module (EORTC QLQ-B23) systemic therapy side effects scale [ Time Frame: From baseline up to 2 years after the end of treatment (up to approximately 7 years) ]
8. Patient-reported quality of life as measured by the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30) global health status/quality of life (GHQ) scale [ Time Frame: From baseline up to 2 years after the end of treatment (up to approximately 7 years) ]
9. Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: Up to 30 days after the end of treatment, approximately 5 years ]
Incidence of participants with TEAEs, SAEs and laboratory abnormalities
10. PK parameter: Plasma concentration of Amcenestrant [ Time Frame: Pre-administration day 1 of cycles 2, 7, 13 and 25 (each cycle is 28 days) ]
Predose plasma concentration of Amcenestrant

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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 are eligible only if they have completed their adjuvant anti-HER2 treatment and chemotherapy.
- With Stage IIB or Stage III (invasive breast cancer) who have undergone breast surgery and adjuvant radiation (if indicated) for the current malignancy.
- Who have 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 is 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

Exclude 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 is not allowed except if the participant has been free from disease for >=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 limit compliance with study requirements
- Treatment with any SERD, tamoxifen or toremifene are 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 are not allowed. Prior treatment with raloxifene or tamoxifen for bone health, risk reduction, or a prior breast cancer is 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 be at least 4 weeks

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

Related Information

• Primary Sponsor: Tanaka Tomoyuki
• Secondary ID(s): NCT05128773,2021-000398-10