Trial record 1 of 56 for:
SERENA 6
Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6) (SERENA-6)
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| ClinicalTrials.gov Identifier: NCT04964934 |
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Recruitment Status :
Recruiting
First Posted : July 16, 2021
Last Update Posted : March 29, 2024
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Sponsor:
AstraZeneca
Information provided by (Responsible Party):
AstraZeneca
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Brief Summary:
The study is intended to show superiority of AZD9833 in combination with CDK4/6 inhibitor (palbociclib, abemaciclib or ribociclib) versus aromatase inhibitors (anastrozole or letrozole) in combination with CDK4/6 inhibitor in patients with hormone receptor-positive (HR-positive), human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer with detectable ESR1 mutation.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| ER-Positive HER2-Negative Breast Cancer | Drug: AZD9833 Drug: AZD9833 Placebo Drug: Anastrozole Drug: Anastrozole placebo Drug: Letrozole Drug: Letrozole placebo Drug: Palbociclib Drug: Abemaciclib Drug: Luteinizing hormone-releasing hormone (LHRH) agonist Drug: Ribociclib | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 300 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Double-blind, Randomised Study to Assess Switching to AZD9833 (a Next Generation, Oral SERD) + CDK4/6 Inhibitor vs Continuing Aromatase Inhibitor (Letrozole or Anastrozole)+ CDK4/6 Inhibitor in HR+/HER2-MBC Patients With Detectable ESR1Mutation Without Disease Progression During 1L Treatment With Aromatase Inhibitor+ CDK4/6 Inhibitor- A ctDNA Guided Early Switch Study |
| Actual Study Start Date : | June 30, 2021 |
| Estimated Primary Completion Date : | January 10, 2025 |
| Estimated Study Completion Date : | November 26, 2027 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
| Arm | Intervention/treatment |
|---|---|
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Experimental: AZD9833 + palbociclib, abemaciclib or ribociclib
The patients will receive AZD9833 (75 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150,100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + anastrozole placebo (PO, once daily) or letrozole placebo (PO, once daily)
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Drug: AZD9833
Dosage formulation: AZD9833 tablets will be administered orally Drug: Anastrozole placebo Dosage formulation: anastrozole placebo tablets will be administrated orally. Drug: Letrozole placebo Dosage formulation: letrozole placebo tablets will be administered orally. Drug: Palbociclib Dosage formulation: palbociclib tablets/capsules will be administered orally Drug: Abemaciclib Dosage formulation: abemaciclib 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. Drug: Ribociclib Dosage formulation: ribociclib tablets will be administered orally |
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Active Comparator: Anastrozole or letrozole + palbociclib, abemaciclib or ribociclib
The patients will recieve anastrozole (1 mg, PO, once daily) or letrozole (2.5 mg, PO, once daily) + palbociclib (PO, once daily, 125, 100 or 75 mg for 21 consecutive days followed by 7 days off treatment), abemaciclib (PO, twice daily, 150, 100 or 50 mg) or ribociclib (To Be Determined, PO, once daily for 21 consecutive days followed by 7 days off treatment) + AZD9833 placebo (PO, once daily)
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Drug: AZD9833 Placebo
Dosage formulation: AZD9833 placebo tablets will be administrated orally. Drug: Anastrozole Dosage formulation: anastrozole tablets will be administered orally. Drug: Letrozole Dosage formulation: letrozole tablets will be administered orally. Drug: Palbociclib Dosage formulation: palbociclib tablets/capsules will be administered orally Drug: Abemaciclib Dosage formulation: abemaciclib 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. Drug: Ribociclib Dosage formulation: ribociclib tablets will be administered orally |
Primary Outcome Measures :
- 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 the earlier of the progression event or death (approximately 2 years) ]PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST 1.1) or death.
Secondary Outcome Measures :
- 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 (approximately 3.5 years) ]PFS2 is defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.
- Overall survival (OS) [ Time Frame: From randomization until the date of death due to any cause (approximately 5 years) ]The OS is defined as the time from randomization to death due to any cause.
- Chemotherapy free survival [ Time Frame: From randomization until the earlier of the start date of chemotherapy or death due to any cause (approximately 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.
- 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 (approximately 5 years) ]ORR is defined as the proportion of patients who have a complete response (CR) or partial response (PR), as determined by the investigator at local site per RECIST 1.1.
- Clinical benefit rate at 24 weeks (CBR24) [ Time Frame: At least 23 weeks after randomisation for each patient (1 week window for RECIST assessment) ]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 randomisation for each patient to allow for an early assessment within the assessment window (1 week window for RECIST assessment)
- Change from baseline in EORTC QLQ-C30 scale scores [ Time Frame: From baseline until second progression (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.
- Change from baseline in EORTC QLQ-BR23 scale scores [ Time Frame: From baseline until second progression (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-BR23). Scale scores range from 0-100. For functioning scales, higher scores indicate better functioning. For symptom scales, higher scores indicate greater symptom burden.
- Plasma concentration of AZD9833 at specified timepoints [ Time Frame: on Day 15 for each patient ]To assess the steady state PK of AZD9833 in combination with palbociclib or abemaciclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration.
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.
| Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
INCLUSION CRITERIA:
INFORMATION FOR TRIAL PARTICIPANTS - Participants can join the trial if they:
- Have advanced breast cancer that is not able to be treated with surgery or radiation;
- Have an ESR1 mutation in their cancer;
- Have breast cancer that is HR-positive and HER2-negative;
- Are currently being treated with a CDK4/6 inhibitor and an AI and have been taking these drugs for at least 6 months;
- Have not had their cancer get worse after taking an AI and CDK4/6 inhibitor;
- Are able to do their daily activities;
- Are at least 18.
Full list of inclusion criteria:
- Proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent;
- Documentation of histologically confirmed diagnosis of estrogen receptor positive (ER+) /HER2- breast cancer based on local laboratory results;
- Currently on AI (letrozole or anastrozole) + CDK4/6 inhibitor (palbociclib, abemaciclib or ribociclib) ± LHRH as the initial endocrine based treatment for advanced disease;
- Eastern Cooperative Oncology Group performance status of 0 or 1;
- ESR1m detected by central testing of ctDNA;
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
- Adequate organ and marrow function.
EXCLUSION CRITERIA:
INFORMATION FOR TRIAL PARTICIPANTS - Participants cannot join the trial if they:
- Had certain types of tumors in the past that may come back;
- Are currently taking any other treatments for their cancer or other conditions including hormone replacements, medications, or supplements that could interfere with the trial treatment;
- Have or have had any major health problem, infection, or recent surgery that could make it difficult or dangerous to participate in this trial.
Full list of exclusion criteria:
- 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 evidence of severe or uncontrolled systemic 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;
- Patient with known or family history of severe heart disease;
- Previous treatment with AZD9833, investigational SERDs or fulvestrant;
- Currently pregnant (confirmed with positive pregnancy test) or breastfeeding;
- Persistent non-haematological toxicities (CTCAE Grade > 2) caused by CDK4/6 inhibitor and/or AI treatment.
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): NCT04964934
Contacts
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Locations
Show 289 study locations
Sponsors and Collaborators
AstraZeneca
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT04964934 |
| Other Study ID Numbers: |
D8534C00001 2023-503990-39-00 ( Other Identifier: EU CT number ) 2021-000546-17 ( EudraCT Number ) |
| First Posted: | July 16, 2021 Key Record Dates |
| Last Update Posted: | March 29, 2024 |
| Last Verified: | March 2024 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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Metastatic Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Physiological Effects of Drugs Randomised Multicentre Double-Blind Phase III AZD9833 Next Generation Oral SERD Anastrozole |
Letrozole Palbociclib Abemaciclib Ribociclib Antagonists Antineoplastic Agents Estrogen Receptor Antagonists Hormone Antagonists camizestrant ESR1m Switch Treatment Endocrine Therapy Endocrine Resistance |
Additional relevant MeSH terms:
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Letrozole Palbociclib Anastrozole Hormones Prolactin Release-Inhibiting Factors Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Antineoplastic Agents |
Aromatase Inhibitors Steroid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Estrogen Antagonists Hormone Antagonists Protein Kinase Inhibitors Antineoplastic Agents, Hormonal |