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Efficacy and Safety of Ribociclib in Pre- and Postmenopausal Chinese Women With HR Positive, HER2-negative, Advanced Breast Cancer.

NCT03671330

Description:

This is a Phase II randomized, double-blind, placebo-controlled study involving premenopausal and postmenopausal Chinese women plus an open-label single arm of pharmacokinetic cohort of LEE011 in combination with Letrozole in Chinese postmenopausal women with HR+, HER2- negative advanced breast cancer. Three cohorts of patients will be enrolled: PK cohort, premenopausal cohort, and postmenopausal cohort.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy and Safety of Ribociclib in Pre- and Postmenopausal Chinese Women With HR Positive, HER2-negative, Advanced Breast Cancer.
  • Official Title: Phase II Randomized, Double-blind, Placebo-controlled Study of LEE011(Ribociclib) or Placebo in Combination With Endocrine Therapy for the Treatment of Pre- and Postmenopausal Chinese Women With HR Positive, HER2-negative, Advanced Breast Cancer, Including a Subset With Pharmacokinetic Analysis.

Clinical Trial IDs

  • ORG STUDY ID: CLEE011A2206
  • NCT ID: NCT03671330

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Ribociclib PlaceboLEE011 PlaceboRibociclib Placebo
RibociclibLEE011Ribociclib
NSAI: Letrozole or AnastrazoleRibociclib
LetrozoleRibociclib
GoserelinRibociclib Placebo

Purpose

This is a Phase II randomized, double-blind, placebo-controlled study involving premenopausal and postmenopausal Chinese women plus an open-label single arm of pharmacokinetic cohort of LEE011 in combination with Letrozole in Chinese postmenopausal women with HR+, HER2- negative advanced breast cancer. Three cohorts of patients will be enrolled: PK cohort, premenopausal cohort, and postmenopausal cohort.

Trial Arms

NameTypeDescriptionInterventions
RibociclibExperimentalPatients in pre- and postmenopausal cohorts will be randomized in the 1:1 ratio to the experimental arm or the control arm. Premenopausal experimental arm: NSAI + Goserelin + Ribociclib; For pre-menopausal only, patient is an adult, female ≥ 18 years old and < 60 years old at the time of informed consent. It is the investigators choice for NSAI based on patient's past medical history. Postmenopausal experimental arm: Letrozole + Ribociclib PK Cohort: Open-label ribociclib + Letrozole treatment combination. For postmenopausal only, patient is an adult, female ≥ 18 years old at the time of informed consent
  • Ribociclib
  • NSAI: Letrozole or Anastrazole
  • Letrozole
Ribociclib PlaceboPlacebo ComparatorPatients in pre- and postmenopausal cohorts will be randomized in the 1:1 ratio to the experimental arm or the control arm. Premenopausal control arm: NSAI + Goserelin + Placebo; For pre-menopausal only, patient is an adult, female ≥ 18 years old and < 60 years old at the time of informed consent. It is the investigators choice for NSAI based on patient's past medical history. Postmenopausal control arm: Letrozole + Placebo For postmenopausal only, patient is an adult, female ≥ 18 years old at the time of informed consent
  • Ribociclib Placebo
  • Ribociclib
  • NSAI: Letrozole or Anastrazole
  • Letrozole
  • Goserelin

Eligibility Criteria

        Inclusion Criteria:

          -  Patient has a histologically and/or cytologically confirmed diagnosis of estrogen
             receptor (ER) positive and/or progesterone receptor positive breast cancer by local
             laboratory (based on most recently analyzed biopsy).

          -  Patient has HER2-negative breast cancer (based on most recently analyzed biopsy)
             defined as a negative in situ hybridization test or an Immunohistochemistry (IHC)
             status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or
             SISH) test is required by local laboratory testing.

          -  Patient must have either:

               -  Measurable disease, i.e., at least 1 measurable lesion as per Response Evaluation
                  Criteria in Solid Tumors (RECIST) 1.1 criteria (a lesion at a previously
                  irradiated site may only be counted as a target lesion if there is a clear sign
                  of progression since the irradiation). OR

               -  If no measurable disease is present, then at least 1 predominantly lytic bone
                  lesion must be present (patients with no measurable disease and only 1
                  predominantly lytic bone lesion that has been previously irradiated are eligible
                  if there is documented evidence of disease progression of the bone lesion after
                  irradiation).

          -  Patient has ECOG performance status 0 or 1.

        For premenopausal cohort:

          -  Patient is an adult, female ≥ 18 years old and < 60 years old at the time of informed
             consent and has signed informed consent before any trial related activities are
             conducted and according to local guidelines.

          -  Confirmed negative serum pregnancy test before starting study treatment or patient has
             had a hysterectomy.

          -  Patient has advanced (loco regionally recurrent not amenable to curative therapy or
             metastatic) breast cancer not amenable to curative therapy (e.g.

        surgery and/or radiotherapy).

          -  Patients who received ≤ 14 days of a NSAI (letrozole or anastrozole) with or without
             goserelin or goserelin ≤ 28 days for advanced breast cancer prior to randomization are
             eligible. Patients must continue treatment with the same hormonal agent + goserelin
             during the study. No treatment interruption is required for these patients prior to
             randomization.

          -  Patients who have received up to 1 line of chemotherapy for advanced breast cancer and
             have been discontinued 28 days before randomization are eligible.

        For postmenopausal cohort:

          -  Patient is an adult, female ≥ 18 years old at the time of informed consent and has
             signed informed consent before any trial related activities and according to local
             guidelines.

          -  Women with advanced (locoregionally recurrent or metastatic) breast cancer not
             amenable to curative therapy.

        Exclusion Criteria:

          -  Patient who has received a prior CDK4/6 inhibitor.

          -  Patient with symptomatic visceral disease or any disease burden that makes the patient
             ineligible for endocrine therapy per the investigator's best judgment

          -  Patient with CNS metastases.

          -  Patient who has not had resolution of clinical and laboratory acute toxicities related
             to prior anti-cancer therapy to National Cancer Institute (NCI) Common Terminology
             Criteria for Adverse Events (CTCAE) version 4.03 Grade ≤1.

          -  Patient has a known history of Human immunodeficiency Virus (HIV) infection (testing
             not mandatory).

          -  Clinically significant, uncontrolled heart disease and/or cardiac repolarization
             abnormality

          -  Patient is currently receiving any of the substances as defined in the protocol that
             cannot be discontinued 7 days prior to the start of the treatment:

        For premenopausal cohort:

          -  Pregnant or nursing (lactating) women.

          -  Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using highly effective methods of contraception
             during dosing of study treatment and for 21 days after stopping study medication.

        Note: Use of oral (estrogen and progesterone), transdermal, injected or implanted hormonal
        methods of contraception as well as hormonal replacement therapy is not allowed in this
        study.

        For postmenopausal cohort:

        - Patient who received any prior systemic anti-cancer therapy (including hormonal therapy
        and chemotherapy) for advanced breast cancer.

        Note: Patients who received neo (adjuvant) therapy for breast cancer are eligible. If the
        prior neo (adjuvant) therapy included letrozole or anastrozole, the disease free interval
        must be greater than 12 months from the completion of treatment until randomization.

        - Patients who received ≤ 14 days of letrozole or anastrozole for advanced disease prior to
        randomization are eligible.

        Other protocol-defined inclusion/exclusion may apply.
      
Maximum Eligible Age:60 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progressive free survival (PFS) based on local assessment by RECIST 1.1 guideline
Time Frame:The primary analysis will be conducted for pre and postmenopausal cohorts separately when approximately 100 PFS events have been observed in pre- and postmenopausal cohorts (approximately 23 months).
Safety Issue:
Description:Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.

Secondary Outcome Measures

Measure:Pharmaconinetic (PK) parameter: Cmax
Time Frame:10 months
Safety Issue:
Description:For PK cohort only. Maximum (peak) concentration of drug in plasma.
Measure:PK parameter: Tmax
Time Frame:10 months
Safety Issue:
Description:For PK cohort only. Time to reach maximum plasma concentration.
Measure:PK parameter: AUC024h
Time Frame:10 months
Safety Issue:
Description:For PK cohort only. Area under the plasma concentration curve versus time.
Measure:Overall Survival (OS)
Time Frame:50 months
Safety Issue:
Description:For pre- and postmenopausal cohorts only. Overall Survival is defined as the time from date of randomization to date of death due to any cause.
Measure:Overall response rate (ORR)
Time Frame:50 months
Safety Issue:
Description:For pre- and postmenopausal cohorts only. Overall response rate is defined as the proportion of patients with best overall response (BOR) of CR or PR according to RECIST 1.1
Measure:Clinical Benefit Rate (CBR)
Time Frame:50 months
Safety Issue:
Description:For pre- and postmenopausal cohorts only. Clinical Benefit Rate is defined as percentage of patients with CR, PR per RECIST or SD lasting 24 weeks or longer, per RECIST 1.1
Measure:Time To Response (TTR)
Time Frame:50 months
Safety Issue:
Description:For pre- and postmenopausal cohorts only. Time to response is defined as the time from the date of randomization to the first documented response either CR or PR, which must be subsequently confirmed (although date of initial response is used, not date of confirmation) according to RECIST 1.1.
Measure:Duration of Response (DoR)
Time Frame:50 months
Safety Issue:
Description:For pre- and postmenopausal cohorts only. Duration of Response applies only to patients whose best overall response is CR or PR according to RECIST1.1.
Measure:Time to deterioration of ECOG performance status from baseline
Time Frame:50 months
Safety Issue:
Description:For pre- and postmenopausal cohorts only. Time to definitive deterioration in ECOG performance status is defined as the time from the date of randomization to the date when ECOG performance status has definitively deteriorated by at least 1 category compared with baseline.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • HR+
  • HER2-
  • breast cancer
  • ribociclib
  • Advanced breast cancer
  • LEE011
  • pre- and postmenopausal Chinese women
  • HR positive
  • HER2-negative
  • Endocrine therapy

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