E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormone receptor-positive, Estrogen and/or progesterone receptor-positive, HER2-negative, High risk early breast cancer |
|
E.1.1.1 | Medical condition in easily understood language |
high risk early breast cancer |
|
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 | LLT |
E.1.2 | Classification code | 10006203 |
E.1.2 | Term | Breast cancer stage unspecified |
E.1.2 | System Organ Class | 100000020819 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070575 |
E.1.2 | Term | Estrogen receptor positive breast cancer |
E.1.2 | System Organ Class | 100000115074 |
|
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 ribociclib + ET versus placebo + ET in patients with HR-positive, HER2-negative, EBC with high risk of recurrence |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the two treatment groups with respect to recurrence-free survival (RFS)
2. To evaluate the two treatment groups with respect to distant disease-free survival (DDFS)
3. To evaluate the two treatment groups with respect to overall survival (OS)
4. To evaluate patients reported outcomes for healthrelated quality of life in the two treatment groups
5. To evaluate safety and tolerability of the treatment regimen |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
● Histologically confirmed unilateral primary invasive adenocarcinoma of the breast
● Estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative breast cancer
● Patient is after surgical resection of the tumor where tumor was removed completely with the final surgical
specimen microscopic margins free from tumor and with available archival tumor tissue from the surgical
specimen
● Patient who received adjuvant chemotherapy and have AJCC 8th edition Prognostic Stage Group III
tumor; or patient who received neoadjuvant chemotherapy and have 1 or more ipsilateral axillary lymph nodes with residual tumor metastases greater than 2.0 mm in lymph node(-s) and residual tumor greater than 10.0 mm in breast tissue
● Patient has completed multi-agent adjuvant or neoadjuvant chemotherapy of ≥ 4 cycles or ≥ 12 weeks which included taxanes prior to screening
● Patient has completed adjuvant radiotherapy (if indicated) prior to screening
● Patient may already have initiated adjuvant endocrine therapy (ET) at the time of randomization, but randomization must take place within 52 weeks of date of initial histological diagnosis of breast cancer and within 12 weeks of initiating ET
● ECOG Performance Status 0 or 1
● Adequate bone marrow and organ function
● Sodium, potassium, phosphorus, magnesium and total calcium laboratory values within normal limits
● QTcF interval < 450 msec and mean resting heart rate 50-90 bpm
Other inclusion criteria as per full protocol may apply. |
|
E.4 | Principal exclusion criteria |
● Prior treatment with CDK4/6 inhibitor
● Prior treatment with tamoxifen, raloxifen or aromatase inhibitors for reduction in risk (chemoprevention) of breast cancer and/or treatment for osteoporosis within last 2 years
● Prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for doxorubicin or 900
mg/m² or more for epirubicin
● Distant metastases of breast cancer beyond regional lymph nodes
● Patient has not recovered from clinical and laboratory acute toxicities of chemotherapy, radiotherapy and surgery
● Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, or clinically
significant cardiac arrhythmias
● Uncontrolled hypertension with systolic blood pressure >160 mmHg
● Patient is currently receiving any of the prohibited substances that cannot be discontinued 7 days prior to Cycle 1 Day 1: concomitant medications, herbal supplements, and/or fruits and their juices that are known as strong inhibitors or inducers of CYP3A4/5; medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5; systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment; concomitant medications with a
known risk to prolong the QT interval and/or known to cause torsades de points that cannot be discontinued
or replaced by safe alternative medication.
● Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed
during the study
● Women of child-bearing potential unless they are using highly effective methods of contraception during the study treatment and for 21 days after stopping the study treatment. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Invasive disease-free survival (iDFS) using STEEP criteria |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Recurrence-free survival (RFS) using STEEP criteria
- Distant disease-free survival (DDFS) using STEEP criteria
- Overall survival (OS)
- Quality of Life (QoL) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
- up to 77 months
- up to 77 months
- up to 77 months
- Baseline and up to 77 months |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
- Patient Reported Outcomes for health-related Quality of Life
- hospital resource utilization |
|
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 | Yes |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 281 |
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 |
Bulgaria |
Canada |
Chile |
China |
Colombia |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Hong Kong |
Hungary |
India |
Ireland |
Israel |
Italy |
Korea, Republic of |
Lebanon |
Mexico |
Netherlands |
Poland |
Romania |
Russian Federation |
Saudi Arabia |
Singapore |
Spain |
Sweden |
Switzerland |
Taiwan |
Thailand |
Turkey |
United Arab Emirates |
United Kingdom |
United States |
|
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
|
If primary endpoint, iDFS is statistically significant at the second interim or at final analysis, data collection will continue and EoS will be declared when 60 m have elapsed from the date the last patient has been randomized. If primary endpoint, iDFS is futile at the first interim analysis, or iDFS is not statistically significant at the final iDFS analysis, EoS will be declared after all patients have discontinued study treatment and completed safety follow-up period |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |