Novartis CLEE011012301C: A phase 3, 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-negative early breast cancer (new adjuvant trial with ribociclib [LEE011]: NATALEE)


A phase 3 multi-center, randomized, open-label trial to evaluate the efficacy and safety of ribociclib with endocrine therapy as adjuvant treatment in patients with HR-positive, HER2-negative early breast cancer.


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Primary Study Objective(s)

The primary objective of this study is to compare invasive disease-free survival for ribociclib plus endocrine therapy versus endocrine therapy in patients with HR-positive, HER2-negative, early breast cancer.

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who:

  • Are 18 years or older at the time of PICF signature
  • Are females with known menopausal status at the time of PICF signature or initiation of adjuvant ET (whichever occurs earlier), or male
  • Have histologically confirmed unilateral primary invasive adenocarcinoma of the breast with a date of initial cytologic or histologic diagnosis within 18 months prior to randomization
  • Have breast cancer that is positive for ER and/or PgR
  • Have HER2-negative breast cancer
  • Have available archival tumor tissue from the surgical specimen
  • Had surgical resection, in which the 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)
  • Have, if indicated, completed adjuvant and/or neoadjuvant chemotherapy according to the institutional guidelines
  • Have, if indicated, completed adjuvant radiotherapy according to the institutional guidelines
  • Have no contraindication for the adjuvant ET in the trial and is planned to be treated with ET for five years

Excluding patients who:

  • Have received any CDK4/6 inhibitor
  • Have received prior treatment with tamoxifen, raloxifene or AIs for reduction in risk ("chemoprevention") of breast cancer and/or treatment for osteoporosis within the last two years prior to PICF signature
  • Have 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
  • Have distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery.
  • Are concurrently using other anti-neoplastic therapy with the exception of adjuvant ET
  • Have had major surgery, chemotherapy or radiotherapy within 14 days prior to randomization
  • Have not recovered from clinical and laboratory acute toxicities related to prior anti-cancer therapies
  • Have a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within two years before PICF signature
  • Have known HIV infection, hepatitis B or C infection
  • Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
  • Are currently receiving any of the following substances within seven 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
  • Are currently receiving or has received systemic corticosteroids ≤ two weeks prior to starting trial treatment
  • Have impairment of GI function or GI disease that may significantly alter the absorption of the oral trial treatments
  • Have 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
  • Have 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 five half-lives of the investigational product, whichever is longer

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Principal Investigator(s)

Eugene Ahn
Cynthia Lynch
Damien Hansra