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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. (SERENA-4)

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ClinicalTrials.gov Identifier: NCT04711252
Recruitment Status : Recruiting
First Posted : January 15, 2021
Last Update Posted : March 4, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
ER-Positive HER2-Negative Breast Cancer Drug: AZD9833 Drug: Anastrozole Drug: Anastrozole placebo Drug: AZD9833 placebo Drug: Palbociclib Drug: Luteinizing hormone-releasing hormone (LHRH) agonist Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1342 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : January 28, 2021
Estimated Primary Completion Date : November 10, 2025
Estimated Study Completion Date : January 30, 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: AZD9833 + palbociclib
The 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)
Drug: AZD9833
Dosage formulation: AZD9833 tablets will be administered orally

Drug: Anastrozole placebo
Dosage formulation: anastrozole placebo tablets will be administrated orally.

Drug: Palbociclib
Dosage formulation: palbociclib tablets will be administered orally

Drug: Luteinizing hormone-releasing hormone (LHRH) agonist
Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.

Active Comparator: Anastrozole + palbociclib
The 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)
Drug: Anastrozole
Dosage formulation: Anastrozole tablets will be administered orally.

Drug: AZD9833 placebo
Dosage formulation: AZD9833 placebo tablets will be administrated orally.

Drug: Palbociclib
Dosage formulation: palbociclib tablets will be administered orally

Drug: Luteinizing hormone-releasing hormone (LHRH) agonist
Men (when medically applicable) and pre- or peri-menopausal women are required to receive a monthly LHRH agonist.




Primary Outcome Measures :
  1. 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) ]
    PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST) or death.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: From randomization until the date of death due to any cause (up to 8 years) ]
    The OS is defined as the time from randomization to death due to any cause.

  2. 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) ]
    PFS2 is defined as the time from randomization to objective tumour progression on next-line treatment or death from any cause.

  3. 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) ]
  4. 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) ]
    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.

  5. 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) ]
    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.

  6. 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) ]
    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.

  7. Clinical benefit rate at 24 weeks (CBR24) [ Time Frame: At least 23 weeks after randomisation ]
    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).

  8. 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) ]
    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.

  9. Plasma concentration of AZD9833 at specified timepoints [ Time Frame: on Day 15 ]
    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.

  10. Change from baseline in EORTC QLQ-C30 scale scores [ Time Frame: From baseline to 24 weeks post progression (up to approximately 5 years) ]
    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.

  11. Change from baseline in EORTC QLQ-BR45 scale scores [ Time Frame: From baseline to 24 weeks post progression (up to approximately 5 years) ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04711252


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04711252    
Other Study ID Numbers: D8532C00001
2020-002276-12 ( EudraCT Number )
First Posted: January 15, 2021    Key Record Dates
Last Update Posted: March 4, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Metastatic
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
camizestrant
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Palbociclib
Anastrozole
Hormones
Prolactin Release-Inhibiting Factors
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Estrogen Antagonists
Hormone Antagonists