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 pretreatment Ki-67 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 (regardless of menopausal status) 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 surgery of the primary breast tumor(s).
•The patient must have tumor tissue from breast (preferred) or lymph node for exploratory 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 Ki-67 status (Cohort 1), or eligible exclusively based on a Ki-67 status (Cohort 2)
•The patient must be randomized within 16 months from the time of definitive breast cancer surgery
•If the patient is currently receiving or initiating standard adjuvant endocrine therapy at time of study entry, she/he may receive up to 12 weeks of endocrine therapy until randomization following the last non-endocrine therapy (surgery, chemotherapy, or radiation), whichever is last.;
•Women of reproductive potential must have a negative blood pregnancy test 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 metastatic disease (including contralateral axillary lymph nodes) or lymph node-negative breast cancer. Patients with inflammatory breast cancer are excluded.
•Patients with a history of previous breast cancer are excluded, with the exception of ipsilateral DCIS treated by locoregional therapy alone ≥5 years ago. Patients with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. Patients with 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 from the date of randomization are excluded.
•Females who are pregnant or lactating
•The patient has previously received treatment with any CDK4 and CDK6 inhibitor.
•The patient is receiving concurrent exogenous reproductive 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 390 events have occured. |
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E.5.2 | Secondary end point(s) |
•Invasive disease-free survival (IDFS) for patients with HR+, HER- early stage breast cancer with pretreatment Ki-67 index ≥20% by central lab
•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 390 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 | 224 |
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 |
Austria |
Belgium |
Brazil |
Canada |
China |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hong Kong |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
New Zealand |
Poland |
Portugal |
Romania |
Russian Federation |
Saudi Arabia |
Singapore |
South Africa |
Spain |
Sweden |
Taiwan |
Turkey |
Ukraine |
United Kingdom |
United States |
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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 |