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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02941926
Recruitment Status : Active, not recruiting
First Posted : October 21, 2016
Last Update Posted : October 6, 2020
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this Phase IIIb 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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Ribociclib Drug: Letrozole Drug: Goserelin Drug: Leuprolide Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3255 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : November 30, 2016
Actual Primary Completion Date : November 8, 2019
Estimated Study Completion Date : May 8, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Ribociclib + letrozole
Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg ribociclib QD + 2.5 mg letrozole QD
Drug: Ribociclib
Ribociclib oral (3 weeks on/1 week off), 600 mg ribociclib QD
Other Name: LEE011

Drug: Letrozole
Oral once daily, 2.5 mg letrozole QD

Drug: Goserelin
Only for men and premenopausal women: administered as an injectable subcutaneous implant once every 28 days

Drug: Leuprolide
Only for men and premenopausal women: administered as an injectable intramuscular depot once every 28 days

Primary Outcome Measures :
  1. The number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to approximately 36 months ]
    AEs, Grade 3/4 AEs & SAEs during treatment with ribociclib + letrozole

Secondary Outcome Measures :
  1. Time-to-Progression (TTP) [ Time Frame: Up to approximately 36 months ]
    Time to progression (TTP) is defined as time from date of start of treatment to the date of event defined as the first documented progression or death due to underlying cancer.

  2. Overall response rate (ORR) for patients with measurable disease [ Time Frame: Up to approximately 36 months ]
    Overall response rate (ORR) is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1.

  3. Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 36 months ]
    Clinical benefit rate (CBR) is defined as the proportion of patients with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. CR, PR and SD are defined according to RECIST 1.1.

  4. Patient Reported Outcome (PRO) using scores from FACT-B questionaire [ Time Frame: Up to approximately 36 months ]
    FACT-B questionnaire will be used to collect patient reported outcome data in this trial. Descriptive statistics will be used to summarize the subscale and overall scores at each scheduled assessment time point. Additionally, change from baseline at the time of each assessment will be summarized. PRO data may be summarized by country/region.

Other Outcome Measures:
  1. The number of participants with adverse events as a measure of safety and tolerability during Extension Phase [ Time Frame: Up to approximatley 18 months ]
    Frequency and severity of AEs and SAEs

  2. Percentage of patients with clinical benefit during Extension Phase [ Time Frame: Up to approximately 18 months ]
    Clinical benefit is assessed by investigator

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 are allowed to be included in this study; menopausal status is relevant for the requirement of goserelin to be used concomitantly with ribociclib and letrozole.

    1. Postmenopausal status is 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 is taking tamoxifen or toremifene and age < 60, then FSH and plasma estradiol levels should 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 are needed to ensure menopausal status.

    2. Premenopausal status is 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 is define as neither premenopausal nor postmenopausal Note: Throughout this document, perimenopausal and premenopausal status is grouped together and referred as "Premenopausal"
  • Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
  • Patient has 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 is required by local laboratory testing.
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  • Patient has 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 has 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 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

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 is permitted


  • 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 study entry.
  • Patients who received ≤ 28 days of letrozole or anastrozole for advanced disease prior to inclusion in this trial are eligible.
  • Any prior (neo) adjuvant anti-cancer therapy or prior chemotherapy for metastatic disease must be stopped at least 5 half-lives or 7 days, whichever is longer, before study inclusion.

    • Patient is concurrently using other anti-cancer therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02941926

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Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals Identifier: NCT02941926    
Other Study ID Numbers: CLEE011A2404
First Posted: October 21, 2016    Key Record Dates
Last Update Posted: October 6, 2020
Last Verified: September 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
HR-positive HER2-negative
advanced breast cancer
Phase IIIb
men with advanced breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal