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A Comparative Study of AZD9833 Plus Palbociclib Versus Anastrozole Plus Palbociclib in Patients With ER-Positive HER2 Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease.

NCT04711252

Description:

The study is intended to show superiority of AZD9833 in combination with palbociclib (a CDK4/6 inhibitor) versus anastrozole (an aromatase inhibitor) and palbociclib as the initial treatment of patients with hormone receptor-positive (ER-positive), human epidermal growth factor 2-negative (HER2-negative) advanced/metastatic breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Comparative Study of AZD9833 Plus Palbociclib Versus Anastrozole Plus Palbociclib in Patients With ER-Positive HER2 Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease.
  • Official Title: SERENA-4: A Randomised, Multicentre, Double-Blind, Phase III Study of AZD9833 (an Oral SERD) Plus Palbociclib Versus Anastrozole Plus Palbociclib for the Treatment of Patients With Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease

Clinical Trial IDs

  • ORG STUDY ID: D8532C00001
  • SECONDARY ID: 2020-002276-12
  • NCT ID: NCT04711252

Conditions

  • ER-Positive HER2-Negative Breast Cancer

Interventions

DrugSynonymsArms
AZD9833AZD9833 + palbociclib
AnastrozoleAnastrozole + palbociclib
Anastrozole placeboAZD9833 + palbociclib
AZD9833 placeboAnastrozole + palbociclib
PalbociclibAZD9833 + palbociclib
Luteinizing hormone-releasing hormone (LHRH) agonistAZD9833 + palbociclib

Purpose

The study is intended to show superiority of AZD9833 in combination with palbociclib (a CDK4/6 inhibitor) versus anastrozole (an aromatase inhibitor) and palbociclib as the initial treatment of patients with hormone receptor-positive (ER-positive), human epidermal growth factor 2-negative (HER2-negative) advanced/metastatic breast cancer.

Detailed Description

      A Randomised, Multicentre, Double-Blind, Phase III study will evaluate the safety and
      efficacy of AZD9833 (next generation oral SERD) in combination with palbociclib versus
      anastrozole in combination with palbociclib for the treatment of patients with ER-positive
      breast cancer. The goal of the study is to demonstrate superiority of AZD9833 over
      anastrozole in the context of combination with palbociclib in first line setting.
    

Trial Arms

NameTypeDescriptionInterventions
AZD9833 + palbociclibExperimentalThe patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (1 mg, PO, once daily)
  • AZD9833
  • Anastrozole placebo
  • Palbociclib
  • Luteinizing hormone-releasing hormone (LHRH) agonist
Anastrozole + palbociclibActive ComparatorThe patients will recieve Anastrozole (1 mg, PO, once daily) + palbociclib (PO, once daily, 125 mg for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)
  • Anastrozole
  • AZD9833 placebo
  • Palbociclib
  • Luteinizing hormone-releasing hormone (LHRH) agonist

Eligibility Criteria

        Inclusion criteria:

          -  Pre-/peri-menopausal women or men can be enrolled if amenable to be treated with
             concomitant, approved LHRH agonists for the duration of the study treatment.

          -  De novo Stage 4 disease, or recurrence from early stage disease after standard
             adjuvant endocrine therapy meeting either one of the following criteria:

               1. Received at least 24 months of AI treatment as part of their adjuvant therapy
                  without disease progression and disease free interval since the last adjuvant
                  treatment must be greater than 12 months

               2. Received at least 24 months of tamoxifen treatment as part of their adjuvant
                  endocrine therapy

          -  Histologically or cytologically documented diagnosis of ER+, HER2-negative breast
             cancer based on local laboratory results.

          -  Previously untreated with any systemic anti-cancer therapy for their locoregionally
             recurrent or metastatic ER+ disease.

          -  Measurable disease as defined per RECIST v.1.1 OR at least one lytic or mixed (lytic +
             sclerotic) bone lesion that can be assessed by CT or MRI.

          -  Eastern Cooperative Oncology Group performance status of 0 or 1.

          -  Adequate organ and marrow function.

          -  Willingness and ability to comply with scheduled visits, treatment plan, laboratory
             tests, and other study procedures.

        Exclusion criteria:

          -  Previous neoadjuvant or adjuvant treatment with an AI treatment +/- CDK4/6 inhibitor
             with disease recurrence while on or within 12 months of completing treatment.

          -  Previous treatment with AZD9833.

          -  Participation in another clinical study with a study treatment or investigational
             medicinal device administered in the last 4 weeks prior to randomization or concurrent
             enrollment in another clinical study, unless it is an observational
             (non-interventional) clinical study or during the follow-up period of an
             interventional study.

          -  Advanced, symptomatic, visceral spread, that are at risk of life-threatening
             complications in the short term.

          -  Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or
             leptomeningeal disease.

          -  Any clinically important and symptomatic heart disease .

          -  Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.

          -  As judged by the investigator, any evidence of diseases (such as severe or
             uncontrolled systemic diseases, renal transplant and active bleeding diseases) which,
             in the investigator's opinion, makes it undesirable for the participant to participate
             in the study or that would jeopardize compliance with the protocol.

          -  Any concurrent anti-cancer treatment.

        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1
Time Frame:From randomization until progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years)
Safety Issue:
Description:PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST) or death.

Secondary Outcome Measures

Measure:Overall survival (OS)
Time Frame:From randomization until the date of death due to any cause (up to 8 years)
Safety Issue:
Description:The OS is defined as the time from randomization to death due to any cause.
Measure:Progression-free survival 2 (PFS2)
Time Frame:From randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death (up to 5 years)
Safety Issue:
Description:PFS2 is defined as the time from randomization to objective tumour progression on next-line treatment or death from any cause.
Measure:Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1
Time Frame:From randomization until a response or in the absence of a response from randomization up until progression, or the last evaluable assessment in the absence of progression (up to 5 years)
Safety Issue:
Description:
Measure:Duration of response (DoR) assessed by the Investigator as defined by RECIST version 1.1
Time Frame:From the date of first documented response until date of documented progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years)
Safety Issue:
Description:The DoR will be defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.
Measure:Time to chemotherapy (TTC)
Time Frame:From randomization until the earlier of the start date of chemotherapy or death due to any cause (up to 5 years)
Safety Issue:
Description:Time to chemotherapy is defined as the time from randomization until the earlier of the start date of chemotherapy or death due to any cause.
Measure:Time to first subsequent anti-cancer therapy (TFST)
Time Frame:From randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause (up to 5 years)
Safety Issue:
Description:TFST is defined as time from randomization until the earlier of start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause.
Measure:Clinical benefit rate at 24 weeks (CBR24)
Time Frame:At least 23 weeks after randomisation
Safety Issue:
Description:CBR at 24 weeks is defined as the percentage of participants who have a complete response (CR) or partial response or who have stable disease (SD) per RECIST 1.1 as assessed by the investigator at local site for at least 23 weeks after randomization (to allow for an early assessment within the assessment window).
Measure:Time to second subsequent therapy (TSST)
Time Frame:From randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause (up to 5 years)
Safety Issue:
Description:TSST is defined as time from randomization until the earlier of start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause.
Measure:Plasma concentration of AZD9833 at specified timepoints
Time Frame:on Day 15
Safety Issue:
Description:To assess the steady state PK of AZD9833 in combination with palbociclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration.
Measure:Change from baseline in EORTC QLQ-C30 scale scores
Time Frame:From baseline to 24 weeks post progression (up to approximately 5 years)
Safety Issue:
Description:Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Scale scores range from 0-100. For functioning and global health status/ QoL scales, higher scores indicate better functioning or global health status/QoL. For symptom scales, higher scores indicate greater symptom burden.
Measure:Change from baseline in EORTC QLQ-BR45 scale scores
Time Frame:From baseline to 24 weeks post progression (up to approximately 5 years)
Safety Issue:
Description:Change from baseline in scales scores of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-BR45). Scale scores range from 0-100. For functioning scales, higher scores indicate better functioning. For symptom scales, higher scores indicate greater symptom burden.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Metastatic
  • Breast Neoplasms
  • Neoplasms by Site
  • Neoplasms
  • Breast Diseases
  • Skin Diseases
  • Hormones, Hormone Substitutes, and Hormone
  • Physiological Effects of Drugs
  • Randomised
  • Multicentre
  • Double-Blind
  • Phase III
  • AZD9833
  • Next Generation Oral SERD
  • Anastrozole
  • Palbociclib
  • Antagonists
  • Antineoplastic Agents
  • Estrogen Receptor Antagonists
  • Hormone Antagonists

Last Updated

January 15, 2021