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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

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ClinicalTrials.gov Identifier: NCT02941926
Recruitment Status : Active, not recruiting
First Posted : October 21, 2016
Last Update Posted : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE October 20, 2016
First Posted Date  ICMJE October 21, 2016
Last Update Posted Date April 8, 2019
Actual Study Start Date  ICMJE November 29, 2016
Estimated Primary Completion Date September 5, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 7, 2017)
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
Original Primary Outcome Measures  ICMJE
 (submitted: October 20, 2016)
The number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to approximately 24 months ]
Incidence of AEs, Grade 3/4 AEs & SAEs during treatment with ribociclib + letrozole
Change History Complete list of historical versions of study NCT02941926 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2017)
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2016)
  • Time-to-Progression (TTP) [ Time Frame: Up to approximately 24 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.
  • Overall response rate (ORR) for patients with measurable disease [ Time Frame: Up to approximately 24 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.
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 24 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.
  • Patient Reported Outcome (PRO) using scores from FACT-B questionaire [ Time Frame: Up to approximately 24 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.
Current Other Pre-specified Outcome Measures
 (submitted: February 7, 2017)
  • The number of participants with adverse events as a measure of safety and tolerability during Extension Phase [ Time Frame: Up to approximatley 30 months ]
    Frequency and severity of AEs and SAEs
  • Percentage of patients with clinical benefit during Extension Phase [ Time Frame: Up to approximately 30 months ]
    Clinical benefit is assessed by investigator
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Ribociclib
    Ribociclib oral (3 weeks on/1 week off) in combination with oral once daily letrozole: 600 mg ribociclib QD + 2.5 mg letrozole QD
    Other Name: LEE011
  • Drug: 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: 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
Study Arms  ICMJE 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
Interventions:
  • Drug: Ribociclib
  • Drug: Letrozole
  • Drug: Goserelin
  • Drug: Leuprolide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 25, 2019)
3253
Original Estimated Enrollment  ICMJE
 (submitted: October 20, 2016)
3000
Estimated Study Completion Date  ICMJE May 21, 2021
Estimated Primary Completion Date September 5, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

      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

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 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE 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
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02941926
Other Study ID Numbers  ICMJE CLEE011A2404
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP