A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer (NATALEE)

• ClinicalTrials.gov Identifier: NCT03701334
• Recruitment Status: Recruiting
• First Posted: October 10, 2018
• Last Update Posted: October 1, 2019
• Sponsor: Novartis Pharmaceuticals
• Collaborator: Translational Research in Oncology
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Early Breast Cancer	Drug: Ribociclib; Other: Endocrine Therapy	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 4000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: December 7, 2018
• Estimated Primary Completion Date: December 26, 2025
• Estimated Study Completion Date: December 26, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ribociclib + Endocrine Therapy; 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	Drug: Ribociclib; Ribociclib + ET; Other: Endocrine Therapy; Endocrine Therapy (ET)
Active Comparator: Endocrine Therapy; endocrine therapy (ET) only once daily continuously	Other: Endocrine Therapy; Endocrine Therapy (ET)

Outcome Measures

Primary Outcome Measures :

1. Invasive Disease-Free Survival [ Time Frame: 3.5 years ]
   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 :

1. Recurrence-free survival [ Time Frame: 3.5 years ]
   using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials)
2. Distant disease-free survival [ Time Frame: 3.5 years ]
   using STEEP criteria (Standardized Definitions for Efficacy End Points in Adjuvant Breast Cancer Trials)
3. Overall Survival [ Time Frame: 7.5 years ]
   overall survival
4. Change from baseline in the global health status Quality of life scale score as assessed by EORTC QLQ-C30 [ Time Frame: 3.5 years ]
   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.
5. Change from baseline in the physical functioning sub-scale score as assessed by EORTC QLQ-C30 [ Time Frame: 3.5 years ]
   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.
6. PK parameter Ctrough and other applicable parameters for ribociclib [ Time Frame: 3.5 years ]
   Pharmacokinetics of ribociclib when given in combination with Non-Steroidal Aromatase Inhibitor (and goserelin if applicable)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 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 an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Patient has no contraindication for the adjuvant ET in the trial and is planned to be treated with ET for 5 years

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

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

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Sponsors and Collaborators

Novartis Pharmaceuticals

Translational Research in Oncology

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03701334 History of Changes
• Other Study ID Numbers: CLEE011O12301C
• First Posted: October 10, 2018
• Last Update Posted: October 1, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

early breast cancer (EBC); HR+/HER2-; adjuvant; LEE011; ribociclib; CDK4/6 inhibitor

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases