COMPLEEMENT-1: An Open-label, Multicenter, Phase IIIb Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With Hormone Receptor-positive (HR+) HER2-negative (HER2-) Advanced Breast Cancer (aBC) With no Prior Hormonal Therapy for Advanced Disease
COMPLEEMENT-1: An Open-label, Multicenter, Phase IIIb Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With Hormone Receptor-positive (HR+) HER2-negative (HER2-) Advanced Breast Cancer (aBC) With no Prior Hormonal Therapy for Advanced Disease
The purpose of this study is to collect additional safety and efficacy data for the combination of ribociclib + letrozole in men and pre/postmenopausal women with HR+HER2- advanced breast cancer and no prior hormonal treatment for advanced disease..
This was an open-label, single arm, multi-center Phase IIIb study. The study was composed of 2 phases: Core Phase and Extension Phase. In the Core Phase, safety and efficacy data was collected. The study treatment during the Core Phase was provided until disease progression, death, unacceptable toxicities, physician's decision, subject/guardian's decision, protocol deviation, study termination by sponsor, lost to follow-up, technical problems or up to 18 months after LPFV.
In the event that patients were still deriving benefit at the end of the Core phase and ribociclib was not approved or available and reimbursed, patients were transitioned to the Extension Phase and continued to receive study treatment until progression, intolerance, death or physician/patient decision. Only safety and clinical benefit (as assessed by investigator) data was collected in the Extension Phase. During the Extension Phase, if ribociclib became locally approved and reimbursed, patients were to be transitioned to prescription. Patients who completed the Extension Phase and continued to derive clinical benefit from the treatment based on the investigator's evaluation received ribociclib from prescription (if approved and reimbursed), another post-trial access program, or other drug access/support program(s).
Canadian sub-study: this sub-study was a multicenter Canadian exploratory correlative sample collection sub-study that aimed to better understand mechanisms of response and resistance to ribociclib in combination with letrozole therapy. This sub-study was available for all Canadian subjects enrolled on the main study and did not alter the planned treatment.
Key Inclusion Criteria:
Male or female advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
In the case of women, both pre/perimenopausal and postmenopausal patients were allowed to be included in this study; menopausal status was relevant for the requirement of goserelin to be used concomitantly with ribociclib and letrozole.
Postmenopausal status was defined either by: I).Prior bilateral oophorectomy OR ii). Age ≥ 60 OR iii). Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range. If patient was taking tamoxifen or toremifene and age < 60, then FSH and plasma estradiol levels would be in post-menopausal range per local normal range (NCCN Guidelines version 2.2017).
Note: For women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol were needed to ensure menopausal status.
Premenopausal status was defined as either: I).Patient had last menstrual period within the last 12 months OR ii). If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range OR iii). In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range.
Perimenopausal status was define as neither premenopausal nor postmenopausal
Patient had a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
Patient had HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test was required by local laboratory testing.
Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤2
Patient had adequate bone marrow and organ function as defined by ALL of the following laboratory values (as assessed by local laboratory):
Patient must have had a 12-lead ECG with ALL of the following parameters at screening:
Key Exclusion Criteria:
Patient who received any CDK4/6 inhibitor
Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of metastatic disease was permitted. Note:
Patient was concurrently using other anti-cancer therapy.
Thomasville, Georgia 31792, United States
Kansas City, Kansas 66160-7330, United States
New Orleans, Louisiana 70121, United States
Baltimore, Maryland 21204-6831, United States
Washington DC, Maryland 20037, United States
Henderson, Nevada 89052, United States
Somerset, New Jersey 08873, United States
Cincinnati, Ohio 45219, United States
Cleveland, Ohio 44106, United States
Milwaukee, Wisconsin 53211, United States
Cheyenne, Wyoming 82001, United States
CABA, Buenos Aires C1125ABD, Argentina
CABA, Buenos Aires C1426ANZ, Argentina
Luxembourg, Luxembourg 1210, Belgium
North York, Ontario M2K1E1, Canada
Plerin Sur Mer, 22190, France
Toulon La Seyne Sur Mer, 83056, France
Pokfulam, Hong Kong, Hong Kong
Hyderabad, Andhra Pradesh 500 034, India
Tamil Nadu, Chennai 600035, India
Admedabad, Gujarat 380060, India
Putrajaya, Kuala Lumpur 62250, Malaysia
Sittard-Geleen, 6162 BG, Netherlands
Leningrad Region, Russia 188663, Russia
Moscow Region Istra Village, 143423, Russia
Moscow Rerion Balashiha, 143900, Russia
Las Palmas de Gran Canarias, Las Palmas de Gran Canaria 35016, Spain
East Sussex, BN2 5BE, United Kingdom