| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| hormone receptor-positive, HER2-negative, early breast cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.0 |
| 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 | 100000004864 |
|
| 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 iDFS for ribociclib + ET versus ET in patients with HRpositive, HER2-negative, EBC |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the two treatment arms with respect to recurrence-free survival (RFS)
2. To evaluate the two treatment arms with respect to distant diseasefree survival (DDFS)
3. To evaluate the two treatment arms with respect to OS
4. To evaluate patient reported outcomes (PRO) for health-related quality of life (QoL) in the two
treatment arms
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- Patient is ≥ 18 years-old at the time of PICF signature
- Patient is female with known menopausal status at the time of randomization or initiation of adjuvant ET (whichever occurs earlier), or male.
- Patient with histologically confirmed unilateral primary invasive adenocarcinoma of the breast with a date of initial cytologic or histologic diagnosis (i.e. date of the pathology report that confirmed the BC diagnosis) within 18 months prior to randomization.
- Patient has breast cancer that is positive for ER and/or PgR
- Patient has HER2-negative breast cancer
- Patient has available archival tumor tissue from the surgical specimen
- Patient after surgical resection where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor, and who belongs to one of the following categories (anatomic stage group II or III)
- If indicated, patient has completed adjuvant and/or neoadjuvant chemotherapy according to the institutional guidelines
- If indicated, patient has completed adjuvant radiotherapy according to the institutional guidelines
- Patient has no contraindication for the adjuvant ET in the trial and is planned to be treated with ET for 5 years |
|
| E.4 | Principal exclusion criteria |
- Patient has received any CDK4/6 inhibitor
- Patient has received prior treatment with tamoxifen, raloxifene or AIs
for reduction in risk ("chemoprevention") of breast cancer and/or
treatment for osteoporosis within the last 2 years prior to
randomization. Patient is concurrently using hormone replacement
therapy.
- Patient has received prior treatment with anthracyclines at cumulative
doses of 450 mg/m² or more for doxorubicin, or 900 mg/m² or more for
epirubicin.
- Patient with a known hypersensitivity to any of the excipients of
ribociclib and/or ET
- Patient with distant metastases of breast cancer beyond regional
lymph nodes (stage IV according to AJCC 8th edition) and/or evidence of
recurrence after curative surgery.
- Patient is concurrently using other anti-neoplastic therapy with the
exception of adjuvant ET
- Patient has had major surgery, chemotherapy or radiotherapy within
14 days prior to randomization
- Patient has not recovered from clinical and laboratory acute toxicities
related to prior anti-cancer therapies
- Patient has a concurrent invasive malignancy or a prior invasive
malignancy whose treatment was completed within 2 years before
randomization
- Patient has known HIV infection, Hepatitis B or C infection
- Clinically significant, uncontrolled heart disease and/or cardiac
repolarization abnormality
- Patient is currently receiving any of the following substances within 7
days before randomization - Concomitant
medications, herbal supplements, and/or fruits that are known as strong
inhibitors or inducers of CYP3A4/5 or Medications that have a narrow
therapeutic window and are predominantly metabolized through
CYP3A4/5
- is currently receiving or has received systemic corticosteroids ≤ 2
weeks prior to starting trial treatment
- Patient has impairment of GI function or GI disease that may
significantly alter the absorption of the oral trial treatments
- Patient has any other concurrent severe and/or uncontrolled medical
condition that would, in the Investigator's judgment, cause unacceptable
safety risks, contraindicate patient participation in the clinical trial or
compromise compliance with the protocol
- Participation in other studies involving investigational drug(s) within
30 days prior to randomization or within 5 half-lives of the
investigational drug(s) (whichever is longer), or participation in any
other type of medical research judged not to be scientifically or
medically compatible with this trial. If the patient is enrolled or planned to be enrolled in another study that does not involve an investigational
drug, the agreement of the Medical Monitor is required to establish
eligibility.
- Pregnant or breast-feeding (lactating) women or women who plan to
become pregnant or breast-feed during the trial.
additional exclusion criteria as per full protocol may apply. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| iDFS using STEEP criteria, as assessed by Investigator |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| up to approximately 44 months |
|
| E.5.2 | Secondary end point(s) |
- recurrence free survival (RFS) using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials)
- Distant disease free survival (DDFS) using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials)
- overall survival (OS)
- Change from baseline in the physical functioning subscale score and global health status/Quality of life scale score as assessed by EORTC QLQ-C30
- PK parameters such as Ctrough and other applicable parameters for ribociclib |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- up to approximately 44 months
- up to approximately 44 months
- up to approximately 91 months
- up to approximately 44 months
- up to approximately 44 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 | No |
| 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 |
| - Quality of life (QoL) and patient reported outcomes (PRO) |
|
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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 | 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 | 11 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 204 |
| 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 |
| France |
| Germany |
| Hungary |
| Ireland |
| Italy |
| Korea, Republic of |
| Peru |
| Poland |
| Romania |
| Russian Federation |
| Spain |
| Taiwan |
| United Kingdom |
| United States |
|
| 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
|
| end of trial will be declared when 60 months + 30 days have elapsed from the date the last patient has been randomized |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 7 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | 4 |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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