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.
Overview
- Phase
- Phase 2
- Intervention
- Ribociclib
- Conditions
- Breast Cancer
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 327
- Locations
- 1
- Primary Endpoint
- Progressive free survival (PFS) based on local assessment by RECIST 1.1 guideline
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief Summary
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.
Investigators
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
- •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.
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 ≤
- •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.
Arms & Interventions
Ribociclib
Patients 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
Intervention: Ribociclib
Ribociclib
Patients 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
Intervention: Letrozole
Ribociclib Placebo
Patients 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
Intervention: Ribociclib Placebo
Ribociclib Placebo
Patients 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
Intervention: Ribociclib
Ribociclib Placebo
Patients 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
Intervention: Letrozole
Ribociclib Placebo
Patients 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
Intervention: Goserelin
Outcomes
Primary Outcomes
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).
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 Outcomes
- Pharmacokinetic (PK) parameter: Cmax(10 months)
- PK parameter: Tmax(10 months)
- PK parameter: AUC024h(10 months)
- Overall Survival (OS)(50 months)
- Overall response rate (ORR)(50 months)
- Clinical Benefit Rate (CBR)(50 months)
- Time To Response (TTR)(50 months)
- Duration of Response (DoR)(50 months)
- Time to deterioration of ECOG performance status from baseline(50 months)