Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With HR+ HER2- aBC

• Register: ClinicalTrials.gov
• Last refreshed on: 6 November 2023
• Main ID: NCT02941926
• Date of registration: 20/10/2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With HR+ HER2- aBC COMPLEEMENT-1
• Scientific title: 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
• Date of first enrolment: November 30, 2016
• Target sample size: 3246
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02941926
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Austria, Belgium, Bulgaria, Canada, Chile, Czechia, Denmark, Finland, France, Greece, Hong Kong, Hungary, India, Israel, Italy, Jordan, Lebanon, Malaysia, Mexico, Netherlands, Norway, Oman, Panama, Philippines, Poland, Portugal, Russian Federation, Saudi Arabia, Singapore, Slovakia, Slovenia, Spain, Sweden, Taiwan, Thailand, United Kingdom, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

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.

1. 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.

2. 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.

3. 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):

- Absolute neutrophil count = 1.5 × 10^9/L

- Platelets = 100 × 10^9/L

- Hemoglobin = 9.0 g/dL

- Potassium, sodium, calcium corrected for serum albumin and magnesium within
normal limits or corrected to within normal limits with supplements before first
dose of the study medication

- INR =1.5

- Serum creatinine <1.5 mg/dl or creatinine clearance=50 mL/min

- In absence of liver metastases, alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) should be below 2.5 × ULN. If the patient had liver
metastases, ALT and AST should be < 5 × ULN.

- Total serum bilirubin < ULN; or total bilirubin = 3.0 × ULN with direct bilirubin
within normal range in patients with well-documented Gilbert's Syndrome

- Patient must have had a 12-lead ECG with ALL of the following parameters at screening:

- QTcF interval at screening <450 msec (using Fridericia's correction)

- Resting heart rate = 50 bpm

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:

- Patients who received (neo) adjuvant therapy for breast cancer were eligible. If
the prior neo (adjuvant) therapy included letrozole or anastrozole the disease
free interval had to be greater than 12 months from the completion of treatment
until study entry.

- Patients who received = 28 days of letrozole or anastrozole for advanced disease
prior to inclusion in this trial were eligible.

- Any prior (neo) adjuvant anti-cancer therapy or prior chemotherapy for metastatic
disease had to be stopped at least 5 half-lives or 7 days, whichever was longer,
before study inclusion.

- Patient was concurrently using other anti-cancer therapy.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: Goserelin

Drug: Leuprolide

Drug: Letrozole

Drug: Ribociclib

Primary Outcome(s)

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment With Ribociclib + Letrozole in the Core Phase [Time Frame: From start of treatment up to 30 days after last treatment (for participants who did not enter to the Extension phase) or up to last treatment in the Core phase (for participants who entered the Extension phase), assessed up to approximately 33 months.]

Secondary Outcome(s)

Clinical Benefit Rate (CBR) Based on Investigator's Assessment (Core Phase) [Time Frame: Up to approximately 33 months]

Number of Participants With AEs and SAEs in the Extension Phase [Time Frame: From first dose of treatment in the Extension phase up to 30 days after last dose of treatment, assessed up approximately 37.6 months]

Change From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Score (Core Phase) [Time Frame: On Day 1 of Cycle 1, 2, 3, 4 ,5, 6, 8, 10, 12 and after that every 3 cycles, and End of treatment, assessed up to 33 months. Cycle=28 days]

Number of Participants With Clinical Benefit (Extension Phase) [Time Frame: On Day 1 of every 3 cycles, starting from Cycle 1 of the Extension phase until end of treatment, assessed up to 37.4 months. Cycle= 28 days]

Overall Response Rate (ORR) Based on Investigator's Assessment (Core Phase) [Time Frame: Up to approximately 33 months]

Time-to-Progression (TTP) Based on Investigator's Assessment (Core Phase) [Time Frame: Up to approximately 33 months]

Secondary ID(s)

CLEE011A2404

2016-003467-19

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 09/05/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02941926