E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer |
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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 | 10006199 |
E.1.2 | Term | Breast cancer stage I |
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 compare invasive disease free survival (IDFS) for patients receiving adjuvant endocrine therapy plus abemaciclib treatment versus adjuvant endocrine therapy alone in HR+, HER2- breast cancer. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy, in terms of IDFS, for patients with Ki67 index ≥20% by central lab
To evaluate the efficacy in terms of distant relapse-free survival (DRFS) and overall survival (OS)
To assess the safety profile
To evaluate the relationship between abemaciclib exposure and clinical (efficacy and safety) outcomes
To evaluate health status, general oncology and breast cancer self-reported health related quality of life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Female or male ≥18 years of age
•The patient has confirmed HR+, HER2-negative (HER2-), early stage resected invasive breast cancer without evidence of distant metastases.
•The patient must have undergone definitive surgical treatment for the current malignancy.
•The patient must have tumor tissue for biomarker analysis available prior to randomization.
•The patient must have high risk of disease recurrence based on nodal status, tumor size, or grade regardless of Ki67 status (Cohort 1), or eligible exclusively based on a Ki67 status (Cohort 2)
•The patient must be randomized within 12 weeks of completion of last non endocrine treatment
•If the patient is currently receiving or initiating standard adjuvant endocrine therapy at time of study entry, she/he must not have received more than 8 weeks prior to randomization.
•Women regardless of menopausal status.
•Women of reproductive potential must have a negative serum pregnancy and agree to use highly effective contraceptive methods
•The patient has a ECOG performance status ≤1
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E.4 | Principal exclusion criteria |
•The patient has Stage IV (M1), Stage IA, and lymph node-negative breast cancer
•The patient has a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 5 years.
•Females who are pregnant or lactating
•The patient has previously received treatment with any CDK4 and CDK6 inhibitor.
•The patient is receiving concurrent exogenous hormone therapy (for example, birth control pills or hormone replacement therapy).
•The patient has previously received endocrine therapy for breast cancer prevention (tamoxifen or raloxifene or aromatase inhibitors).
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare invasive disease free survival (IDFS) for patients receiving adjuvant endocrine therapy plus abemaciclib treatment versus adjuvant endocrine therapy alone in HR+, HER2- breast cancer. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After approximately 5 years when approximately 345 events have occured. |
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E.5.2 | Secondary end point(s) |
•Primary: invasive disease-free survival (IDFS) as defined by the STEEP System (Hudis et al. 2007)
•Efficacy endpoints: distant relapse-free survival (DRFS), overall survival (OS)
•Safety endpoints will include but are not limited to the following: TEAEs, SAEs, and hospitalizations Clinical laboratory tests, vital signs, and physical examinations
•Steady-state trough abemaciclib concentration (Cmin,ss), hazard ratio for IDFS, DRFS, OS, other efficacy and safety endpoints
•Composite and single-item endpoints will be evaluated to examine differentiating effects of abemaciclib across study arms. Measurement will be undertaken using the FACT-B questionnaire for general oncology and breast cancer health-related quality of life; the FACT-ES subscale and additional FACIT-sourced items for cognitive and bladder endocrine therapy symptoms; and the FACIT-F subscale to characterize this symptom know to be associated with oncology, endocrine therapy, and abemaciclib treatment.
•The EQ-5D-5L health state profile (the index score and the single-item health status measure) will be used to inform decision modeling for economic evaluations and this questionnaire will be coadministered with and after first completing the FACT/FACIT questionnaire, subscales, and additional items.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After approximately 5 years when approximately 345 events have occured.
At the end of trial. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 181 |
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 |
Hong Kong |
India |
Israel |
Japan |
Korea, Republic of |
Mexico |
New Zealand |
Saudi Arabia |
South Africa |
Taiwan |
United States |
Austria |
Finland |
France |
Poland |
Sweden |
Netherlands |
Romania |
Spain |
Czechia |
Germany |
Greece |
Italy |
Belgium |
Denmark |
Hungary |
Russian Federation |
Turkey |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 10 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 10 |