Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04964934
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	AstraZeneca
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Australia, Austria, Belgium, Bulgaria, Canada, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Norway, Poland, Portugal, Russian Federation, Slovakia, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	ER-Positive HER2-Negative Breast Cancer

Additional Details

Breast cancer is the most common type of cancer among women. In people with breast cancer, the body is not able to control the growth of some cells. These extra cells can form tumors in the breast. When tumor cells move to different parts of the body this is called advanced cancer. Researchers are looking for better ways to treat advanced breast cancer. This trial will look at six drugs: palbociclib, abemaciclib, ribociclib, letrozole, anastrozole, and AZD9833. AZD9833 is the trial drug, and is the only drug not yet approved for use. Palbociclib, abemaciclib and ribociclib work in the same way and are a type of cancer drug called a CDK4/6 inhibitor. Letrozole and anastrozole work in the same way and are both a type of cancer drug called an aromatase inhibitor (AI). CDK4/6 inhibitors and AIs work together to block the tumor's ability to grow. These drugs have been approved for combined use in people with advanced breast cancer that is HR-positive and HER2-negative. But if people get mutations in the ESR1 gene, it can make the AI and CDK4/6 inhibitor treatment work less well. The trial drug, AZD9833, is designed to work with a CDK4/6 inhibitor in the same way that an AI does. Researchers think that AZD9833 might work better with a CDK4/6 inhibitor than an AI does in people who get mutations in their ESR1 gene. Participants in this trial will have already been receiving one of the following combinations of a CDK4/6 inhibitor and an AI:

- palbociclib + anastrozole.

- palbociclib + letrozole.

- abemaciclib + anastrozole.

- abemaciclib + letrozole.

- ribociclib + anastrozole.

- ribociclib + letrozole.

During the trial, participants will remain on the same CDK4/6 inhibitor that they were taking before the trial. In this trial, the researchers want to find out how well switching a participant with an ESR1 gene mutation from an AI (letrozole or anastrozole) to AZD9833 works in the treatment of advanced breast cancer that is HR-positive and HER2-negative. The researchers will look at which trial treatment helps the participants live longer with the cancer before it gets worse. The researchers also want to know more about how safe AZD9833 is. The trial participants will be split into 2 groups:

- Participants in Group A will receive AZD9833, a CDK4/6 inhibitor, and a placebo.

- Participants in Group B will receive an AI, a CDK4/6 inhibitor, and a placebo.

A placebo looks like a treatment but does not have any medicine in it. A computer program will be used to randomly choose the treatments each participant gets. This helps make sure the groups are chosen fairly. Researchers do this so that comparing the results of each treatment will be as accurate as possible. The participants will take their trial treatments over 28-day cycles, with a placebo and either AZD9833 or an AI taken once daily by mouth for all 28 days. If the participant is taking abemaciclib, they will take it twice daily by mouth for all 28 days. If the participant is taking palbociclib or ribociclib, they will take it once daily by mouth for 21 days and then stop taking it for the final 7 days of the cycle. The participant will then repeat the 28-day cycle receiving the trial treatment in the same way for as long as they are in the trial. Participants will visit their trial site regularly throughout the trial. At these visits, the trial doctors will check the health of the participants. They will also take blood samples and do scans of the participants' tumors. Participants will take their trial treatment until their cancer gets worse or they decide to leave the trial. *Palbociclib and Abemacliclib cohorts are currently ongoing. Ribociclib cohort will be open pending on availability of the data.

Arms & Interventions

Arms

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)

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)

Interventions

Drug: - AZD9833

Dosage formulation: AZD9833 tablets will be administered orally

Drug: - AZD9833 Placebo

Dosage formulation: AZD9833 placebo tablets will be administrated orally.

Drug: - Anastrozole

Dosage formulation: anastrozole tablets will be administered orally.

Drug: - Anastrozole placebo

Dosage formulation: anastrozole placebo tablets will be administrated orally.

Drug: - Letrozole

Dosage formulation: letrozole tablets will be administered 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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Research Site, Phoenix, Arizona

Status

Recruiting

Address

Research Site

Phoenix, Arizona, 85054

Site Contact

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