Clinical Trials /

Ribociclib-endocrine Combination Therapy Versus Chemotherapy as 1st Line in Visceral mBC

NCT03905343

Description:

The aim of this trial is to assess if patients treated with the combination of ribociclib and endocrine therapy respond to treatment as fast as patients treated with chemotherapy only, without decreasing their quality of life (QoL).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Ribociclib-endocrine Combination Therapy Versus Chemotherapy as 1st Line in Visceral mBC
  • Official Title: Ribociclib-endocrine Combination Therapy Versus Chemotherapy as 1st Line Treatment in Patients With Visceral Metastatic Breast Cancer. A Multicenter, Randomized Phase III Trial.

Clinical Trial IDs

  • ORG STUDY ID: SAKK 21/18
  • SECONDARY ID: 2018-003648-22
  • NCT ID: NCT03905343

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
RibociclibA: endocrine therapy + ribociclib

Purpose

The aim of this trial is to assess if patients treated with the combination of ribociclib and endocrine therapy respond to treatment as fast as patients treated with chemotherapy only, without decreasing their quality of life (QoL).

Detailed Description

      Breast cancer is the most frequent malignancy in women and the leading cause of cancer
      mortality in most countries in Europe. Metastatic breast cancer remains an incurable disease
      with a median overall survival (OS) of 2-4 years and a 5-year survival of only 25%. Patients
      with hormone receptor (HR)-positive breast cancer involving visceral disease at diagnosis
      have an even worse outcome.

      Many oncologists still prefer to treat visceral disease primarily with chemotherapy rather
      than with endocrine treatment, thinking to receive a faster response with chemotherapy than
      with endocrine therapy, especially in patients with clinical symptoms or potentially
      threatening lesions. However, results from cross-sectional clinical practice studies suggest
      that endocrine therapy is associated with better quality of life, fewer concerns about side
      effects, less activity impairment and higher treatment satisfaction compared to chemotherapy.
      In addition, with the new data of CDK4/6 inhibitors combined with endocrine treatment there
      is an even better efficacy data available compared to endocrine therapy alone.

      The aim of this trial is to assess if patients treated with the combination of ribociclib and
      endocrine therapy respond to treatment as fast as patients treated with chemotherapy only,
      without decreasing their quality of life (QoL).
    

Trial Arms

NameTypeDescriptionInterventions
A: endocrine therapy + ribociclibExperimental
  • Ribociclib
B: mono-chemotherapyActive Comparator

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Written informed consent according to national law and ICH/GCP regulations before
                 registration and prior to any trial specific procedures
    
              -  Histologically or cytologically confirmed diagnosis of HR-positive (ER+ ≥10%),
                 HER2-negative advanced stage breast cancer
    
              -  Measurable visceral disease according to RECIST v1.1. Visceral disease in liver and/or
                 lung. Peritoneal and/or pleural metastases only are accepted, with the condition to be
                 measurable
    
              -  No previous systemic anticancer therapy for metastatic disease allowed
    
              -  Mono-chemotherapy is a reasonable treatment option
    
              -  Patients with a prior malignancy and treated with curative intention are eligible if
                 all treatment of that malignancy was completed at least 2 years before randomization
                 and the patient has no evidence of disease at randomization. Less than 2 years is
                 acceptable for adequately treated cervical carcinoma in situ or localized non-melanoma
                 skin cancer
    
              -  Patients with asymptomatic and stable (treated or untreated) central nervous system
                 (CNS) metastases are eligible, provided they meet the following criteria:
    
                   -  ≤ 5 CNS lesions with a maximum diameter of the largest lesion of 10 mm
    
                   -  No evidence of progression at registration compared to the latest brain imaging
                      (if applicable)
    
                   -  No ongoing requirement for corticosteroids as therapy for CNS disease
    
              -  Baseline QoL and pain questionnaires have been completed within 21 days prior to
                 registration
    
              -  Postmenopausal women (without ovarian function suppression)
    
              -  Age ≥ 18 years
    
              -  WHO performance status 0-2
    
              -  Adequate bone marrow function: neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x
                 109/L, hemoglobin ≥ 90 g/L
    
              -  Adequate hepatic function: bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's
                 disease ≤ 3.0 x ULN), AST ≤ 2.5 x ULN, AP ≤ 2.5 x ULN
    
              -  Adequate renal function: estimated glomerular filtration rate (eGFR) > 40
                 mL/min/1.73m2 (according to CKD-EPI or MDRD formula)
    
              -  Patient is able and willing to swallow trial drug as whole tablet
    
            Exclusion Criteria:
    
              -  Visceral crisis (clinical judgment of treating investigator based on the ABC
                 consensus: "visceral crisis is defined as severe organ dysfunction as assessed by
                 signs and symptoms, laboratory studies, and rapid progression of disease. Visceral
                 crisis is not the mere presence of visceral metastases, but implies important visceral
                 compromise leading to a clinical indication for a more rapidly efficacious therapy,
                 particularly since another treatment option at progression will probably not be
                 possible")
    
              -  Symptomatic brain metastases indicative of active disease (defined as new and/or
                 progressive brain metastases at the time of study entry) or leptomeningeal disease
    
              -  Any prior systemic anti-cancer treatment for advanced stage breast cancer
    
              -  Prior treatment with adjuvant CDK4/6 inhibitor
    
              -  Concurrent or recent (within 30 days of randomization) treatment with any other
                 experimental drug. Exception: participation in SAKK 96/12 is allowed
    
              -  Concomitant use of other anti-cancer drugs or radiotherapy, except for local pain
                 control
    
              -  Planned surgery of metastatic sites in the first 12 treatment weeks
    
              -  Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or
                 IV), unstable angina pectoris, history of myocardial infarction within the last six
                 months, serious arrhythmias requiring medication (with exception of atrial
                 fibrillation or paroxysmal supraventricular tachycardia)
    
              -  Electrocardiogram (ECG) abnormalities of Q-wave infarction (unless identified ≥ 6
                 months prior to randomization), or QTc interval >450 msec. The use of concomitant
                 medications with a known significant risk of prolonging the QT interval or inducing
                 Torsades de pointes is not allowed
    
              -  Any concomitant drugs contraindicated for use with the trial drugs according to the
                 approved national product information
    
              -  Known hypersensitivity to trial drug(s) or to any component of the trial drug(s)
    
              -  Any other serious underlying medical, psychiatric, psychological, familial or
                 geographical condition, which in the judgment of the investigator may interfere with
                 the planned staging, treatment and follow-up, affect patient compliance or place the
                 patient at high risk from treatment-related complications
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:Female
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Quality of life-adjusted early disease control
    Time Frame:at 12 weeks.
    Safety Issue:
    Description:A patient will be counted as a success for this endpoint when during the first 12 weeks - the response according to RECIST v1.1 is stable disease or better.

    Secondary Outcome Measures

    Measure:Disease Control (DC) at 12 weeks
    Time Frame:week 6, 12.
    Safety Issue:
    Description:A patient will be counted as a success for this endpoint when during the first 12 weeks the response according to RECIST v1.1 is stable disease or better. Patients with missing response assessments within the first 12 weeks will be counted as failure unless there was no progressive disease (PD) documented within the first 12 weeks and the first subsequent assessment also shows no PD
    Measure:Objective response rate (ORR)
    Time Frame:week 6, 12, then every 12 weeks up to 3 years or end of trial treatment.
    Safety Issue:
    Description:ORR is defined as the proportion of patients having achieved complete response (CR) or partial response (PR) during trial treatment. Response will be evaluated according to RECIST v1.1 criteria.
    Measure:Time to objective response (OR)
    Time Frame:week 6, 12, then every 12 weeks up to 3 years or end of trial treatment.
    Safety Issue:
    Description:Time to OR will be calculated from randomization until first documented CR or PR according to RECIST v1.1 criteria. Time to OR will be calculated for patients having achieved a CR or PR at any time during trial treatment.
    Measure:Progression-free survival (PFS)
    Time Frame:week 6, 12, then every 12 weeks up to 3 years.
    Safety Issue:
    Description:PFS is defined as the time from randomization until progression according the RECIST v1.1 criteria or death from any cause, whichever occurs first. Patients not having an event at the time of analysis as well as patients starting a new anti-cancer therapy in the absence of an event will be censored at the date of their last tumor assessment before starting a new anti-cancer treatment, if any.
    Measure:Time to treatment failure (TTF)
    Time Frame:week 6, 12, then every 12 weeks up to 3 years.
    Safety Issue:
    Description:TTF is defined as the time from randomization until stopping of trial treatment from any cause. Patients not having an event at the time of analysis will be censored at the date of their last known date of trial treatment.
    Measure:Overall survival (OS) at 3 years
    Time Frame:week 6, 12, then every 12 weeks up to 3 years.
    Safety Issue:
    Description:OS at 3 years is determined by the Kaplan-Meier estimator for OS at 3 years. OS is defined as time from randomization to death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive.
    Measure:Changes in overall QoL (FACT-B) until 24 months
    Time Frame:Changes from baseline to 24 months
    Safety Issue:
    Description:Changes in Functional Assessment of Cancer Therapy-Breast (FACT-B) total score (score range 0-148, higher scores indicate better quality of life)
    Measure:Time to QoL deterioration
    Time Frame:From baseline to 24 months
    Safety Issue:
    Description:Time to QoL deterioration is defined as the duration between baseline and first occurrence of a decrease of ≥ 5 points in the FACT-TOI score.
    Measure:Time to QoL improvement
    Time Frame:From baseline to 24 months
    Safety Issue:
    Description:Time to QoL improvement is defined as the duration between baseline and first occurrence of an increase of ≥ 5 points in the FACT-TOI score.
    Measure:Time to pain improvement
    Time Frame:From baseline to 24 months
    Safety Issue:
    Description:Improvements in pain will be assessed up to 24 months by the item pain severity of the Brief Pain Inventory (BPI), scale range: 0= no pain to 10 = pain as bad as one can imagine.
    Measure:Adverse events (AEs)
    Time Frame:every 4 weeks up to 3 years.
    Safety Issue:
    Description:All AEs will be assessed according to NCI CTCAE v5.0.

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Swiss Group for Clinical Cancer Research

    Trial Keywords

    • breast cancer
    • Visceral metastatic breast cancer
    • Ribociclib
    • Ribociclib-endocrine

    Last Updated