Clinical Trials /

Adjuvant Palbociclib in Elderly Patients With Breast Cancer

NCT03609047

Description:

Phase II study to assess the efficacy of the combination of at least 5 year endocrine therapy and 2 year-palbociclib as adjuvant systemic treatment instead of adjuvant chemotherapy followed by endocrine therapy in older patients with stage II-III ER+/HER2- early breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Palbociclib in Elderly Patients With Breast Cancer
  • Official Title: A Phase II Study of Adjuvant PALbociclib as an Alternative to CHemotherapy in Elderly patientS With High-risk ER+/HER2- Early Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: EORTC 1745-ETF-BCG
  • NCT ID: NCT03609047

Conditions

  • Breast Cancer Stage II
  • Breast Cancer Stage III

Interventions

DrugSynonymsArms
Palbociclibexperimental palbociclib arm
Docetaxel / cyclophosphamidecontrol chemotherapy arm
doxorubicin/cyclophosphamidecontrol chemotherapy arm
epirubicin/cyclophosphamidecontrol chemotherapy arm
paclitaxelcontrol chemotherapy arm

Purpose

Phase II study to assess the efficacy of the combination of at least 5 year endocrine therapy and 2 year-palbociclib as adjuvant systemic treatment instead of adjuvant chemotherapy followed by endocrine therapy in older patients with stage II-III ER+/HER2- early breast cancer.

Detailed Description

      The primary objective of this trial is to assess the efficacy of the combination of at least
      5 year endocrine therapy and 2 year-palbociclib as adjuvant systemic treatment instead of
      adjuvant chemotherapy followed by endocrine therapy in older patients with stage II-III
      ER+/HER2- early breast cancer.

      This is a two-arm open-label multi-center randomized (2:1) non-comparative phase II study in
      elderly patients with stage II/III, ER+, HER2- early breast cancer for whom treatment with
      chemotherapy is indicated.

      Patients will be randomized with a 2:1 allocation rate to the following treatment arm:

        -  experimental palbociclib arm: Standard adjuvant endocrine therapy for a duration of at
           least 5 years + palbociclib for a total duration of up to 2 years.

        -  control chemotherapy arm: adjuvant chemotherapy (4 cycles of
           docetaxel/doxorubicin/epirubicin-cyclophosphamide; or of weekly paclitaxel D1, D8, and
           D15 q3w if a 3 weekly schedule is not desired), followed by standard adjuvant endocrine
           therapy for a duration of at least 5 years.

      The primary endpoint of the study is the 3-year D-RFI rate in the experimental arm.
    

Trial Arms

NameTypeDescriptionInterventions
experimental palbociclib armExperimentalStandard adjuvant endocrine therapy for a duration of at least 5 years + palbociclib (one capsule 125mg QD, orally, for 21 days followed by 7 days off treatment) for a total duration of up to 2 years.
  • Palbociclib
control chemotherapy armActive ComparatorAdjuvant chemotherapy: 4 cycles docetaxel 75 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles doxorubicin 60 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles epirubicin 90 mg/m2 / cyclophosphamide 600 mg/m2 q3w OR 4 cycles weekly paclitaxel 80 mg/m2 D1, D8, and D15 q3w Followed by standard adjuvant endocrine therapy for a duration of at least 5 years.
  • Docetaxel / cyclophosphamide
  • doxorubicin/cyclophosphamide
  • epirubicin/cyclophosphamide
  • paclitaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Women or men with stage II or stage III, early invasive breast cancer according to the
             UICC 8th edition for TNM classification

          -  Histologically confirmed Estrogen Receptor ER+ (at least 10 % of cells staining
             positive for ER), Human Epidermal Growth Factor Receptor 2 (HER-2) negative, early
             invasive breast cancer based on results of local pathology. Testing may be performed
             on diagnostic core biopsy or resection specimen.

          -  In patients with multicentric, multifocal and/or bilateral breast cancer, all
             histopathologically examined invasive tumors must meet pathologic criteria regarding
             ER and HER2-status described above.

          -  Adjuvant chemotherapy indicated and feasible according to treating physician and
             patient, based on standard clinicopathological parameters (tumor size, lymph node
             involvement, general health status, proliferation marker, patient wish) and gene
             expression profile if available.

          -  Adjuvant chemotherapy combining both anthracycline and taxanes considered not
             indicated or not feasible according to treating physician.

          -  No evidence of macroscopic distant metastases, investigated according to local
             institutional guidelines.

          -  Age ≥70 years

          -  Eastern Cooperative Oncology Group (ECOG) Performance status 0-2

          -  Patient must have undergone breast +/- axillary surgery with curative intent for the
             current malignancy ≤8 weeks before randomization.

          -  The maximum duration from last surgery to the start of the first adjuvant treatment is
             9 weeks.

          -  Patients must have sufficient resolution of any surgical side effects from the last
             surgery per physician assessment, with no active wound healing complications at the
             time of randomization.

          -  Incentive to undergo adjuvant radiation therapy when indicated per local institutional
             guidelines.

          -  Note: For patients in the palbociclib arm, radiation therapy when indicated has to
             start ≤9 weeks after last surgery. The endocrine therapy can be initiated during or
             after the radiation therapy but not later than 3 weeks after the last radiotherapy.
             Palbociclib has to start ≤3 weeks after the last radiotherapy. When radiation therapy
             is not indicated, endocrine therapy and palbociclib have to be initiated ≤9 weeks
             after last surgery.

          -  Note: For patients in the chemotherapy arm, chemotherapy has to be the first adjuvant
             treatment and has to start ≤9 weeks after the last surgery. When radiation therapy is
             indicated, this treatment has to start ≤6 weeks after the last chemotherapy
             administration. Adjuvant endocrine therapy can be initiated during or after the
             radiation therapy but not later than 3 weeks after the last radiotherapy. When
             radiation therapy is not indicated, endocrine therapy has to be initiated ≤6 weeks
             after last chemotherapy administration.

          -  Adequate organ function, evidenced by the following laboratory results within 3 weeks
             prior to inclusion:

          -  Hemoglobin ≥ 9 g/dL

          -  Absolute neutrophil count (ANC) ≥ 1500/mm3

          -  Platelet count ≥ 100,000/mm3

          -  Total bilirubin ≤ 1.5 upper limit of normal (ULN), or total bilirubin ≤ 3.0 × ULN in
             patients with documented Gilbert's Syndrome.

          -  Glomerular Filtration Rate (GFR) ≥ 30 ml/min according to Modification of Diet in
             Renal Disease (MDRD) formula or Chronic Kidney Disease - Epidemiology Collaboration
             (CKD-EPI) formula or Cockcroft and Gault formula

          -  Serum Glutamic Oxaloacetic Transaminase (Aspartate Transaminase), Serum Glutamic
             Pyruvic Transaminase (Alanine Transaminase) and alkaline phosphatase ≤ 2.5 × ULN

          -  Patients must be able and willing to swallow and retain oral medication without a
             condition that would interfere with enteric absorption.

          -  Absence of any psychological, familial, sociological or geographical condition
             potentially hampering compliance with the study protocol and follow-up schedule; those
             conditions should be discussed with the patient before registration in the trial

          -  Before patient registration/randomization, written informed consent must be obtained
             according to ICH/GCP, and national/local regulations.

        Exclusion Criteria:

          -  Previous history of invasive breast cancer

          -  Systemic anticancer therapy prior to the breast cancer surgery

          -  Prior therapy with any Cyclin-Dependent Kinase (CDK)4/6 inhibitor

          -  Concurrent investigational agent within 28 days of randomization

          -  Concomitant anticancer treatment with the exception of bone antiresorptive agents or
             Luteinizing Hormone-Releasing Hormone agonists in male patients treated with an
             aromatase-inhibitor

          -  History of allergic reactions attributed to compounds of chemical or biological
             composition similar to palbociclib or to chemotherapy components

          -  Medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes
             within 7 days of randomization (see Chapter 5.6.3 for list of CYP3A inhibitors and
             inducers)

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection (including known HIV, active hepatitis B and/or hepatitis C infection),
             symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac
             arrhythmia, or uncontrolled diabetes.

          -  Other malignancy within the last 5 years except: adequately treated non-metastatic
             non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal
             carcinoma in situ of the breast.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:70 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:distant recurrence-free interval (D-RFI) rate
Time Frame:5 years after first patient inclusion
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Breast cancer specific survival
Time Frame:5 years after first patient inclusion
Safety Issue:
Description:
Measure:Overall survival
Time Frame:5 years after first patient inclusion
Safety Issue:
Description:
Measure:Incidence of permanent treatment discontinuation
Time Frame:5 years after first patient inclusion
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:European Organisation for Research and Treatment of Cancer - EORTC

Trial Keywords

  • Breast cancer
  • elderly patients
  • CDK4/6 inhibitor

Last Updated

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