Description:
A phase III multi-center, randomized, open-label trial to evaluate efficacy and safety of
ribociclib with endocrine therapy as adjuvant treatment in patients with HR+/HER2- Early
Breast Cancer
Title
- Brief Title: A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer
- Official Title: A Phase III Multi-center, Randomized, Open-label Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as an Adjuvant Treatment in Patients With Hormone Receptor-positive, HER2-negartive Early Breast Cancer (New Adjuvant TriAl With Ribociclib [LEE011]: NATALEE)
Clinical Trial IDs
- ORG STUDY ID:
CLEE011O12301C
- NCT ID:
NCT03701334
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Ribociclib | | Ribociclib + Endocrine Therapy |
Purpose
A phase III multi-center, randomized, open-label trial to evaluate efficacy and safety of
ribociclib with endocrine therapy as adjuvant treatment in patients with HR+/HER2- Early
Breast Cancer
Trial Arms
Name | Type | Description | Interventions |
---|
Ribociclib + Endocrine Therapy | Experimental | ribociclib 400 mg once daily on days 1-21 of a 28 day cycle followed by 7 days off" and endocrine therapy (ET) once daily continuously | |
Endocrine Therapy | Active Comparator | endocrine therapy (ET) only once daily continuously | |
Eligibility Criteria
Inclusion
- 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
Exclusion
- 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Invasive Disease-Free Survival |
Time Frame: | 3.5 years |
Safety Issue: | |
Description: | Invasive Disease-Free Survival for ribociclib + Endocrine Therapy versus Endocrine Therapy in patients with HR-positive, HER2-negative Early Breast Cancer using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials), as assessed by Investigator |
Secondary Outcome Measures
Measure: | Recurrence-free survival |
Time Frame: | 3.5 years |
Safety Issue: | |
Description: | using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials) |
Measure: | Distant disease-free survival |
Time Frame: | 3.5 years |
Safety Issue: | |
Description: | using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials) |
Measure: | Overall Survival |
Time Frame: | 7.5 years |
Safety Issue: | |
Description: | overall survival |
Measure: | Change from baseline in the global health status Quality of life scale score as assessed by EORTC QLQ-C30 |
Time Frame: | 3.5 years |
Safety Issue: | |
Description: | The EORTC QLQ-C30 contains functional scales, symptom scales, single items scale and a global health status/QoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. |
Measure: | Change from baseline in the physical functioning sub-scale score as assessed by EORTC QLQ-C30 |
Time Frame: | 3.5 years |
Safety Issue: | |
Description: | The EORTC QLQ-C30 contains functional scales, symptom scales, single items scale and a global health status/QoL scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. |
Measure: | PK parameter Cmax for ribociclib |
Time Frame: | 3.5 years |
Safety Issue: | |
Description: | Pharmacokinetics of ribociclib when given in combination with Non-Steroidal Aromatase Inhibitor (and goserelin if applicable) |
Measure: | PK parameter Tmax for ribociclib |
Time Frame: | 3.5 years |
Safety Issue: | |
Description: | Pharmacokinetics of ribociclib when given in combination with Non-Steroidal Aromatase inhibitor (and goserelin if applicable) |
Measure: | PK parameter AUC0-24 for ribociclib |
Time Frame: | 3.5 years |
Safety Issue: | |
Description: | Pharmacokinetics of ribociclib when given in combination with Non-Steroidal Aromatase inhibitor (and goserelin if applicable) |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- early breast cancer (EBC)
- HR+/HER2-
- adjuvant
- LEE011
- ribociclib
- CDK4/6 inhibitor
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