E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine whether amcenestrant once a day (QD) improves the invasive breast cancer-free survival (IBCFS) when compared to tamoxifen QD in patients with early breast cancer as adjuvant treatment |
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E.2.2 | Secondary objectives of the trial |
•To determine whether amcenestrant once a day (QD) improves the invasive disease-free survival (IDFS) when compared to tamoxifen QD in patients with early breast cancer as adjuvant treatment •To evaluate the distant recurrence-free survival (DRFS) in both treatment arms •To evaluate the locoregional recurrences-free survival (LRRFS) in both treatment arms •To evaluate the overall survival (OS) in both treatment arms •To evaluate the breast cancer-specific survival (BCSS) in both treatment arms •To evaluate patient-reported overall treatment-related side effect bother, treatment-related symptoms, and quality of life in both treatment arms •To evaluate safety in both treatment arms •To characterize the pharmacokinetics (PK) of amcenestrant
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 2 receptor (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
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E.4 | Principal 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 for which they received an 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 selective estrogen receptor degrader (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
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Invasive breast cancer-free survival (IBCFS)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) From randomization up to approximately 10 years
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E.5.2 | Secondary end point(s) |
1)Invasive disease-free survival (IDFS) 2)Distant recurrence-free survival (DRFS) 3)Locoregional recurrences-free survival (LRRFS) 4)Overall survival (OS) 5)Breast cancer-specific survival (BCSS) 6)Patient-reported overall treatment-related side effect bother as measured by the Functional Assessment of Cancer Therapy Item GP-5 (FACT-GP5) 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 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 9)Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) 10)PK parameter: Plasma concentration of Amcenestrant |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/2/3/4/5)From randomization up to approximately 10 years 6)From baseline up to 2 years after the end of treatment (up to approximately 7 years) 7)From baseline up to 2 years after the end of treatment (up to approximately 7 years) 8)From baseline up to 2 years after the end of treatment (up to approximately 7 years) 9)Up to 30 days after the end of treatment, approximately 5 years 10)Pre-administration day 1 of cycles 2, 7, 13 and 25 (each cycle is 28 days)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 140 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Brazil |
Canada |
Chile |
China |
India |
Japan |
Korea, Republic of |
Mexico |
New Zealand |
Taiwan |
United States |
Austria |
Estonia |
France |
Sweden |
Spain |
Switzerland |
Germany |
Greece |
Italy |
Belgium |
Denmark |
Georgia |
Hungary |
Ireland |
Portugal |
Russian Federation |
Turkey |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 12 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 12 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |