A phase III multi-center, randomized, open-label trial to evaluate efficacy and safety of ribociclib withendocrine therapy as adjuvant treatment in patients with HR+/HER2- Early Breast Cancer

Phase 1

• Conditions: hormone receptor-positive, HER2-negative, early breast cancer; MedDRA version: 20.0Level: LLTClassification code 10006203Term: Breast cancer stage unspecifiedSystem Organ Class: 100000004864; MedDRA version: 20.1Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002998-21-HU
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-02-25
• Last Update Posted: 29 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 4000

Inclusion Criteria

- Patient is = 18 years-old at the time of PICF
signature
- Patient is female with known menopausal status at the time of PICF signature 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 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2000
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2000

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 PICF signature
- 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 PICF signature
- 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
- Patient participated in another interventional study
and received treatment with an investigational product (or used an investigational device) within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer.
- 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare iDFS for ribociclib + ET versus ET in patients with HRpositive, HER2-negative, EBC;Secondary Objective: 1. To evaluate the two treatment arms with respect to recurrence-free survival (RFS)<br>2. To evaluate the two treatment arms with respect to distant diseasefree survival (DDFS)<br>3. To evaluate the two treatment arms with respect to OS<br>4. To evaluate patient reported outcomes (PRO) for health-related quality of life (QoL) in the two<br>treatment arms<br>5. To characterize the PK of ribociclib when given in combination with NSAI (and goserelin if applicable);Primary end point(s): iDFS using STEEP criteria, as assessed by Investigator;Timepoint(s) of evaluation of this end point: 3.5 years

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - recurrence free survival (RFS) using STEEP criteria<br>(Standardized Definitions for Efficacy End Points in<br>Adjuvant Breast Cancer Trials)<br>- Distant disease free survival (DDFS) using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials)<br>- overall survival (OS)<br>- Change from baseline in the physical functioning subscale score and global health status/Quality of life scale score as assessed by EORTC QLQ-C30<br>- PK parameters such as Cmax, Tmax, and AUC0- 24h for ribociclib;Timepoint(s) of evaluation of this end point: - 3.5 years<br>- 3.5 years<br>- 7.5 years<br>- 3.5 years<br>- 3.5 years