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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

Short name COMPLEEMENT-1

NCTNCT02941926 (opens ClinicalTrials.gov in a new tab)Other idCLEE011A2404Other id2016-003467-19Other id2016

Overview

Status
Completed
Phase
Phase 3
Enrollment
3,246 participants (actual)
Sponsor
Novartis Pharmaceuticals · Industry
Design
Allocation not applicable · Open label (no masking)
Countries
30 countries

United States, 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, Russia, Saudi Arabia

Start
30 Nov 2016
Primary completion
8 Nov 2019
Completion
9 Nov 2022
First posted
21 Oct 2016 (estimated)
Last update posted
24 Oct 2023
Conditions
Breast Cancer

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2016201820202022
  1. Ph 3

    COMPLEEMENT-1

    NCT02941926

    30 Nov 2016 to 9 Nov 2022

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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..

Interventions

  • RibociclibDrug
  • LetrozoleDrug
  • GoserelinDrug
  • LeuprolideDrug

Arms1

  • Experimental

    Ribociclib + letrozole+goserelin/leuprolide

    Participants received ribociclib (orally taken, 3 weeks on/1 week off) in combination with letrozole (orally taken once daily). For men and premenopausal women, either goserelin was given as an injectable subcutaneous implant or leuprolide was given as an intramuscular injection.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. 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.

    Registry description

    AEs were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s). SAEs were defined as meeting at least 1 of the following criteria: is fatal or life-threatening, Results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, requires inpatient hospitalization or prolongation of existing hospitalization. A SAE which caused death of the participant was considered as fatal SAE. AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 to 5 were used to characterize the severity of the Adverse Event. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening and Grade 5: death related to AE. A participant with multiple severity grades for an AE is only counted under the maximum grade.

Secondary outcomes(6)
  1. Time-to-Progression (TTP) Based on Investigator's Assessment (Core Phase)

    Time frame · Up to approximately 33 months

    Registry description

    Time to progression (TTP) is defined as time from date of start of treatment to the date of first documented progression or death due to underlying cancer. Participants with symptoms of rapidly progressing disease without radiologic evidence were classified as progression only when clear evidence of clinical deterioration was documented and/or patient discontinued due to 'Disease progression' or death due to study indication. When there was no documentation of radiologic evidence of progression, and the patient discontinued for 'Disease progression' due to documented clinical deterioration of disease, the date of discontinuation was used as date of progression. TTP was estimated using the Kaplan-Meier method. 95% CI of median was calculated according to Brookmeyer and Crowley method.

  2. Overall Response Rate (ORR) Based on Investigator's Assessment (Core Phase)

    Time frame · Up to approximately 33 months

    Registry description

    Overall response rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 based on investigator's assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. 95% CI was calculated using the exact binomial method.

  3. Clinical Benefit Rate (CBR) Based on Investigator's Assessment (Core Phase)

    Time frame · Up to approximately 33 months

    Registry description

    Clinical benefit rate (CBR) is defined as the percentage of participants 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 based on investigator's assessment. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease. 95% CI was calculated using the exact binomial method.

  4. 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

    Registry description

    Change from baseline in FACT-B scores was assessed. FACT-B is a self-report instrument that measures multidimensional quality of life (QOL) in patients with breast cancer. The FACT-B consists of 37 questions that address physical, social, emotional, and functional well-being, with specific questions relevant to women with breast cancer. Each item has a score range of 0 (Not at all) to 4 (Very much), with a total score ranging from 0-148. The higher the score, the better the QOL reported by the participant. A positive change from baseline indicates improvement in QoL. Due to the nature of the questionnaire, only females were asked to complete this questionnaire.

  5. 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

    Registry description

    AEs were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s). SAEs were defined as meeting at least 1 of the following criteria: is fatal or life-threatening, Results in persistent or significant disability/incapacity, constitutes a congenital anomaly/birth defect, is medically significant, requires inpatient hospitalization or prolongation of existing hospitalization. AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 to 5 were used to characterize the severity of the Adverse Event. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening and Grade 5: death related to AE. A participant with multiple severity grades for an AE is only counted under the maximum grade.

  6. 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

    Registry description

    Clinical benefit as assessed by the Investigator during Extension phase

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· 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.

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Treatment With Ribociclib + Letrozole in the Core Phase

GroupValue (Participants)
Ribociclib + Letrozole + Goserelin/Leuprolide3203
Secondary and other outcome results(7)
Secondary outcomeMedian· Up to approximately 33 months

Time-to-Progression (TTP) Based on Investigator's Assessment (Core Phase)

GroupValue (Months)
Ribociclib + Letrozole + Goserelin/Leuprolide27.1
Secondary outcomeNumber· Up to approximately 33 months

Overall Response Rate (ORR) Based on Investigator's Assessment (Core Phase)

GroupValue (Percentage of participants)
Ribociclib + Letrozole + Goserelin/Leuprolide29.3
Secondary outcomeNumber· Up to approximately 33 months

Clinical Benefit Rate (CBR) Based on Investigator's Assessment (Core Phase)

GroupValue (Percentage of participants)
Ribociclib + Letrozole + Goserelin/Leuprolide70.7
Secondary outcomeMean· 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

Change From Baseline in Functional Assessment of Cancer Therapy - Breast (FACT-B) Score (Core Phase)

GroupValue (Score on a scale)Spread
Ribociclib + Letrozole + Goserelin/Leuprolide0.213.29
Secondary outcomeCount of participants· From first dose of treatment in the Extension phase up to 30 days after last dose of treatment, assessed up approximately 37.6 months

Number of Participants With AEs and SAEs in the Extension Phase

GroupValue (Participants)
Ribociclib + Letrozole + Goserelin/Leuprolide297
Secondary outcomeCount of participants· 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

Number of Participants With Clinical Benefit (Extension Phase)

GroupValue (Participants)
Ribociclib + Letrozole + Goserelin/Leuprolide413
Other pre specified outcomeMean· Screening (up to 28 days before first dose of study treatment)

Canadian Sub-study: Proteomic Analysis of Ribociclib and Letrozole Cohort Not Achieving Clinical Benefit Compared to a Cohort Sensitive to Treatment With Ribociclib and Letrozole

GroupValue (log2 transformed relative ratio)Spread
Primary Resistance Cohort0.1120.500
Sensitive Cohort-0.2180.352

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
All Patients- On-treatment Core PhaseAEs collected in the on-treatment period of the core phase (up to 30 days after last treatment for participants who did not enter the Extension phase or up to last treatment in the Core phase for participants who entered the Extension phase)74 / 3246702 / 32463150 / 3246
All Patients- On-treatment Extension PhaseAEs collected in the on-treatment period of the Extension phase (from first dose of treatment in the Extension phase up to 30 days after last dose of treatment)5 / 41354 / 413247 / 413
All-patients- Post-treatment Survival Follow-up Core PhaseDeaths collected in the post-treatment survival follow-up period (starting from 31 days post-treatment in the Core phase). No AEs were collected during this period90 / 27590 / 00 / 0
All-patients- Post-treatment Survival Follow-up Extension PhaseDeaths collected in the post-treatment survival follow-up period (starting from 31 days post-treatment in the Extension phase). No AEs were collected during this period3 / 4080 / 00 / 0

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies3

Studies that cite this trial.

More studies

3 studies on this page

Indexing hint: Clinical trial · 2022

Ribociclib plus letrozole in male patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: subgroup analysis of the phase IIIb CompLEEment-1 trial.

Campone et al. 2022Breast cancer research and treatmentcited by 10

PMID 35212906DOI 10.1007/s10549-022-06543-1PUB-35212906

Full text at the publisher
Publisher page

Indexing hint: Clinical trial · 2022

Safety and Efficacy of Ribociclib in Combination with Letrozole in Patients with HR+, HER2- Advanced Breast Cancer: Results from the Italian Subpopulation of Phase 3b CompLEEment-1 Study.

De Laurentiis et al. 2022Targeted oncologycited by 4

PMID 36152144PMC9684264DOI 10.1007/s11523-022-00913-xPUB-36152144

Free to read · publisher termsCC BY-NC
Read at source

Indexing hint: Clinical trial · 2021

Corrected

Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population.

De Laurentiis et al. 2021Breast cancer research and treatmentcited by 28

PMID 34414532PMC8505291DOI 10.1007/s10549-021-06334-0PUB-34414532

CC BY

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedCaputo R, Fabi A, Romagnoli E, Baldini E, Grasso D, Fenderico N, Michelotti A. Ribociclib Plus Letrozole in Italian Male Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Case Studies of Phase 3b CompLEEment-1 Trial. Breast Cancer (Dove Med Press). 2022 Oct 18;14:351-362. doi: 10.2147/BCTT.S376902. eCollection 2022. PMID 36267663
  • DerivedSalvador Bofill J, Moreno Anton F, Rodriguez Sanchez CA, Galve Calvo E, Hernando Melia C, Ciruelos Gil EM, Vidal M, Jimenez-Rodriguez B, De la Cruz Merino L, Martinez Janez N, Villanueva Vazquez R, de Toro Salas R, Anton Torres A, Alvarez Lopez IM, Gavila Gregori J, Quiroga Garcia V, Vicente Rubio E, De la Haba-Rodriguez J, Gonzalez-Santiago S, Diaz Fernandez N, Barnadas Molins A, Cantos Sanchez de Ibarguen B, Delgado Mingorance JI, Bellet Ezquerra M, de Casa S, Gimeno A, Martin M. Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2- advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial. Breast. 2022 Dec;66:77-84. doi: 10.1016/j.breast.2022.09.006. Epub 2022 Sep 28. PMID 36206609

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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