Clinical Trials /

Ribociclib and Aromatase Inhibitor or Paclitaxel and Bevacizumab for Metastatic Breast Cancer in First Line

NCT03462251

Description:

This study is designed to evaluate the efficacy and safety of first-line treatment ribociclib in combination with aromatase inhibitor (AI) or paclitaxel with / without bevacizumab in patients with HR-positive, HER2-negative advanced breast cancer with visceral metastasis. Half of the patients will receive a combination of ribociclib and AI while the other half will receive paclitaxel +/- bevacizumab.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Ribociclib and Aromatase Inhibitor or Paclitaxel and Bevacizumab for Metastatic Breast Cancer in First Line
  • Official Title: A Randomized, Open-label, Multicenter, Two-arm, Phase III Study to Evaluate Efficacy and Quality of Life in Postmenopausal Patients With Metastatic HR-positive HER2-negative Breast Cancer Receiving Ribociclib in Combination With Aromatase Inhibitor or Paclitaxel With or Without Bevacizumab in First Line

Clinical Trial IDs

  • ORG STUDY ID: IOM-050371
  • NCT ID: NCT03462251

Conditions

  • Breast Cancer
  • Hormone Receptor Positive Tumor
  • HER 2 Negative Breast Cancer

Purpose

This study is designed to evaluate the efficacy and safety of first-line treatment ribociclib in combination with aromatase inhibitor (AI) or paclitaxel with / without bevacizumab in patients with HR-positive, HER2-negative advanced breast cancer with visceral metastasis. Half of the patients will receive a combination of ribociclib and AI while the other half will receive paclitaxel +/- bevacizumab.

Detailed Description

      This is a prospective, randomized, open-label, two-arm, multicenter, interventional phase III
      trial in Germany. The study will include adult, postmenopausal women with HR-positive,
      HER2-negative advanced breast cancer with visceral metastases, who received no prior therapy
      for advanced disease.

      160 patients will be enrolled and randomized 1:1 (stratified by the presence of lung and / or
      liver metastases) to receive Arm A: a combination of ribociclib and AI; OR Arm B: paclitaxel
      +/- bevacizumab

      Treatment will be continued until disease progression, intolerable toxicity or death.
      Progression-free survival (PFS) will be based on tumor assessments by local
      radiologists/investigator using RECIST v1.1 criteria. Treatment might be continued beyond
      RECIST-defined progressive disease (PD) in case of negligible or clinically irrelevant
      disease progression according to the investigator's discretion until clinically relevant
      disease progression or symptomatic deterioration.
    

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalCombination of ribociclib and aromatase inhibitor
    Arm BActive ComparatorPaclitaxel +/- bevacizumab

      Eligibility Criteria

              Inclusion Criteria:
      
                -  Age ≥ 18 years.
      
                -  Postmenopausal women
      
                -  Locally confirmed diagnosis of metastatic adenocarcinoma of the breast without prior
                   systemic antineoplastic therapy in the palliative setting.
      
                -  Hormone receptor (HR)-positive disease, defined as estrogen receptor (ER)-positive
                   and/or progesterone receptor (PgR)-positive.
      
                -  Human epidermal growth factor receptor 2 (HER2)-negative disease (defined as
                   immunohistochemistry (IHC) status HER2 negative/+ or IHC HER2++ with chromosomal in
                   situ hybridization (CISH)/fluorescent in situ hybridization (FISH) negative).
      
                -  Presence of visceral metastases (additional non-visceral metastases are allowed).
      
                -  Presence of target and / or non-target lesions according to RECIST v1.1
      
                -  Patients eligible for palliative treatment with AI + ribociclib and paclitaxel +/-
                   bevacizumab according to the respective summary of product characteristics (SmPCs).
      
                -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
      
                -  Adequate organ and bone marrow function within 7 days prior to randomization.
      
                -  Standard 12-lead ECG values: QT Interval Corrected by the Fridericia Correction
                   Formula (QTcF) interval at screening < 450 msec; Mean resting heart rate 50-90 bpm
                   (determined from the ECG)
      
                -  Signed written informed consent prior to beginning of protocol-specific procedures.
      
              Exclusion Criteria:
      
                -  Any prior systemic palliative therapy
      
                -  Prior treatment with any cyclin-dependent kinase 4/6 (CDK4/6) inhibitor.
      
                -  Prior adjuvant therapy with AI if last intake within 12 months prior to entering the
                   study.
      
                -  Prior adjuvant or neoadjuvant taxane therapy if last application within 12 months
                   prior to entering the study.
      
                -  Patient is concurrently using other anti-cancer therapy.
      
                -  Patient has had major surgery within 28 days prior to randomization or has not
                   recovered from major side effects or wound is not fully recovered.
      
                -  Patient has received extended-field radiotherapy ≤ 4 weeks or limited-field
                   radiotherapy ≤ 2 weeks prior to randomization.
      
                -  Known hypersensitivity to ribociclib, AI, paclitaxel, bevacizumab or any of their
                   excipients, or against peanut, soya, Chinese hamster ovarian cell products or
                   macrogolglycerol ricinoleate-35.
      
                -  Clinically significant, uncontrolled heart disease and/or cardiac repolarization
                   abnormality (e.g. history of myocardial infarction within 6 months prior study entry,
                   long QT syndrome, clinically significant cardiac arrhythmias or systolic blood
                   pressure > 140 or < 90 mmHg or diastolic blood pressure > 90 mmHg).
      
                -  Patient has history of arterial thrombosis within 12 months prior to entering the
                   study.
      
                -  Patient has proteinuria (≥ 2+ on urine dipstick)
      
                -  Patient with congenital bleeding diathesis, acquired coagulopathy or under full dose
                   of anticoagulants.
      
                -  Patient is currently receiving strong inducers or inhibitors of CYP3A4/5 or medication
                   with narrow therapeutic window that are predominantly metabolized through CYP3A4/5 and
                   cannot be discontinued 7 days prior to start of study treatment.
      
                -  Known presence of cerebral metastases unless at least 4 weeks from prior therapy
                   completion (including radiation and/or surgery) to starting the study treatment and
                   clinically stable central nervous system tumor at the time of screening.
      
                -  Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for
                   treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight
                   heparin (LMWH), or fondaparinux is allowed.
      
                -  Patient is currently receiving or has received systemic corticosteroids or other
                   chronic immunosuppressive therapy ≤ 2 weeks prior to starting study drug.
      
                -  Patients with advanced symptomatic, visceral spread, that are at risk of
                   lifethreatening complications in the short term (including patients with massive
                   uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and
                   over 50% liver involvement).
      
                -  Patient has a known history of HIV infection (testing not mandatory).
      
                -  Patient has active untreated or uncontrolled fungal, bacterial or viral infection.
      
                -  Patient has any other concurrent severe and/or uncontrolled medical condition that
                   would, in the investigator's judgment, cause unacceptable safety risks, contraindicate
                   patient participation in the clinical study or compromise compliance with the protocol
                   (e.g. chronic pancreatitis, chronic active hepatitis, etc.).
      
                -  Participation in prior investigational studies within 30 days prior to randomization
                   or within 5-half lives of the investigational product, whichever is longer.
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:Female
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Efficacy in terms of PFS
      Time Frame:Up to approximately 15 months.
      Safety Issue:
      Description:PFS is defined as time from randomization to progression of disease or death of any cause, whichever comes first. It will be assessed by imaging until progressive disease or start of next-line therapy.

      Secondary Outcome Measures

      Measure:Overall Survival (OS)
      Time Frame:Up to approximately 48 months.
      Safety Issue:
      Description:OS is defined as time from randomization to death of any cause.
      Measure:Overall Response Rate (ORR)
      Time Frame:Up to approximately 15 months.
      Safety Issue:
      Description:ORR is defined as the proportion of patients with best overall response of complete or partial response according to RECIST 1.1.
      Measure:Clinical Benefit Rate (CBR)
      Time Frame:Up to approximately 15 months
      Safety Issue:
      Description:CBR is defined as the proportion of patients with best overall response of complete or partial response or stable disease lasting 24 weeks or more according to RECIST 1.1.
      Measure:Time To Response (TTR)
      Time Frame:Up to approximately 15 months.
      Safety Issue:
      Description:TTR is defined as time from randomization to first occurrence of any response (complete or partial) according to RECIST 1.1.
      Measure:Number of participants with Adverse Events
      Time Frame:Until 30 days after end of treatment, up to approximately 16 months.
      Safety Issue:
      Description:Type, frequency and severity (according to CTCAE v4.03) of adverse events
      Measure:Time to deterioration of ECOG performance status
      Time Frame:Until 30 days after end of treatment, up to approximately 16 months
      Safety Issue:
      Description:Time to deterioration of ECOG performance status by at least one point from baseline.
      Measure:Tolerability of treatment
      Time Frame:Until 30 days after end of treatment, up to approximately 16 months.
      Safety Issue:
      Description:By-patient listings of safety laboratory (hemoglobin, platelets, white blood cells with differentials, international normalized ratio , serum creatinine, bilirubin, Alanine-Aminotransferase (ALT) and Aspartate-Aminotransferase (AST)).
      Measure:corrected QT interval (QTc) time
      Time Frame:Until 30 days after end of treatment, up to approximately 16 months.
      Safety Issue:
      Description:By-patient listings of cardiac monitoring.
      Measure:Health-related quality of life (QoL)
      Time Frame:Up to 36 months.
      Safety Issue:
      Description:Health-related QoL will be assessed with the EORTC Quality of life questionnaire (QLQ) QLQ-C30.
      Measure:Side effects of treatment
      Time Frame:Up to 36 months.
      Safety Issue:
      Description:One question on treatment burden
      Measure:Time spent on treatment
      Time Frame:Up to 36 months
      Safety Issue:
      Description:Burden by treatment will be assessed with 4 questions on time spent on treatment

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:iOMEDICO AG

      Trial Keywords

      • Breast Cancer
      • HR positive
      • HER2 negative
      • Mamma carcinoma

      Last Updated

      April 4, 2018