Clinical trial NCT03671330: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: HR+
HER2-
breast cancer
ribociclib
Advanced breast cancer
LEE011
pre- and postmenopausal Chinese women
HR positive
HER2-negative
Endocrine therapy
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-09-14
Enrollment: 327
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Progressive free survival (PFS) based on local assessment by RECIST 1.1 guideline
timeFrame: 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).
Secondary outcomes:
measure: Pharmacokinetic (PK) parameter: Cmax
timeFrame: 10 months
measure: PK parameter: Tmax
timeFrame: 10 months
measure: PK parameter: AUC024h
timeFrame: 10 months
measure: Overall Survival (OS)
timeFrame: 50 months
measure: Overall response rate (ORR)
timeFrame: 50 months
measure: Clinical Benefit Rate (CBR)
timeFrame: 50 months
measure: Time To Response (TTR)
timeFrame: 50 months
measure: Duration of Response (DoR)
timeFrame: 50 months
measure: Time to deterioration of ECOG performance status from baseline
timeFrame: 50 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Novartis Investigative Site
state: Anhui
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Chongqing
country: China
facility: Novartis Investigative Site
state: Chongqing
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shijiazhuang
country: China
facility: Novartis Investigative Site
state: Hebei
city: Harbin
country: China
facility: Novartis Investigative Site
state: Heilongjiang
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Suzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanchang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Chang Chun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Shengyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Shengyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Xian
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Kunming
country: China
facility: Novartis Investigative Site
state: Yunnan
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Fuzhou
country: China
facility: Novartis Investigative Site
city: Qingdao
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: