Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Disease Progression

Breast Diseases

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Letrozole

Estrogens

Palbociclib

Prolactin Release-Inhibiting Factors

Anastrozole

Aromatase Inhibitors

Hormone Antagonists

Estrogen Antagonists

Estrogen Receptor Antagonists

Enzyme Inhibitors

Protein Kinase Inhibitors

Antineoplastic Agents, Hormonal

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)

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)

Dosage formulation: AZD9833 tablets will be administered orally

AZD9833

Dosage formulation: AZD9833 placebo tablets will be administrated orally.

AZD9833 Placebo

Dosage formulation: anastrozole tablets will be administered orally.

Dosage formulation: anastrozole placebo tablets will be administrated orally.

Anastrozole placebo

Dosage formulation: letrozole tablets will be administered orally.

Dosage formulation: letrozole placebo tablets will be administered orally.

Letrozole placebo

Dosage formulation: palbociclib tablets/capsules will be administered orally

Dosage formulation: abemaciclib tablets will be administered orally

Abemaciclib

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

Luteinizing hormone-releasing hormone (LHRH) agonist

Dosage formulation: ribociclib tablets will be administered orally

Ribociclib

AstraZeneca Clinical Study Information Center

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.

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.

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

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

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.

PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST 1.1) or death.

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.

The OS is defined as the time from randomization to death due to any cause.

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.

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.

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 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 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.

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.

AstraZeneca

Skin Diseases

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)

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)

Dosage formulation: Anastrozole tablets will be administered orally.

AZD9833 placebo

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.

INFORMATION FOR TRIAL PARTICIPANTS

In this trial, the researchers will look at how well camizestrant with palbociclib works, compared with anastrozole with palbociclib, in participants with breast cancer that has either spread into other parts of the body at the time of diagnosis, or has come back after at least 2 years of standard endocrine treatment.

Participants in this trial will have breast cancer that has ER proteins but does not have overexpression of HER2 protein.

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.

INFORMATION FOR TRIAL PARTICIPANTS

Researchers are looking for a better way to treat breast cancer.

In people with cancer, some cells have grown out of control to form tumours.

The trial drugs palbociclib, camizestrant, and anastrozole are designed to work by blocking the cancer's ability to grow. Camizestrant is also called AZD9833. Palbociclib and anastrozole are already available as treatments for people with certain type of breast cancer.

In this trial, the researchers want to find out how well taking camizestrant with palbociclib, or anastrozole with palbociclib, works in participants with breast cancer that has ER proteins but does not have overexpression of HER2 protein.

The researchers will look at which trial treatments help the participants live longer with cancer before it gets worse.

The trial will split participants into 2 groups:

* Participants in Group 1 will take camizestrant, palbociclib, and a placebo matched with anastrazole.
* Participants in Group 2 will take anastrozole, palbociclib, , and a placebo matched with camizestrant.

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 in periods called "cycles". Each cycle will last 28 days. During each cycle, the participants will take:

* camizestrant or anastrozole once daily by mouth
* palbociclib once daily by mouth for 21 days. Then, they will not take any palbociclib for 7 days

Some participants will also get either goserelin or leuprorelin once every month. Participants could get goserelin or leuprorelin if:

* They are medically determined yet to reach menopause status
* They are male

They will get this treatment as an injection under the skin or into a muscle. Goserelin and leuprorelin work by decreasing the amount of sex hormones made by the body which will lead to reduction of ER production. This can help stop breast cancer from growing.

Participants will take trial treatment until the cancer gets worse or they leave the trial.

Participants will visit their trial site several times 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.

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: 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

PFS is defined as the time from randomization to objective disease progression (as assessed by RECIST) or death.

Time to second progression or death (PFS2) will be defined as the time from randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.

ORR is defined as the proportion of patients who have a CR or partial response, as determined by the investigator at local site per RECIST 1.1.

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.

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.

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).

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.

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.

Change from baseline in EORTC QLQ-C30 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score.

Change from baseline in EORTC QLQ-BR45 scale scores for each patient at each post-baseline visit. The comparison will include all randomised patients, as randomised, with baseline and at least one post-baseline visit score for the scale score.

Carcinoma

Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 1 of the study.

Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 1 of the study.

Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 2 of the study.

Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 2 of the study.

Post-menopausal participants will receive once daily oral dose C of AZD9833 in stage 2 of the study.

Post-menopausal participants will receive once daily oral dose A of AZD9833 in stage 3 of the study.

Post-menopausal participants will receive once daily oral dose B of AZD9833 in stage 3 of the study.

AZD9833 tablets will be administered orally.

John Robertson

This is a randomised, open-label, parallel-group, pre-surgical study aimed to investigate the biological effects, safety, tolerability, and pharmacokinetics (PK) of different doses of oral AZD9833 in post-menopausal women with primary breast cancer

The study will be conducted in approximately 20 study centers across 3 countries and will be conducted in three stages (stage 1, stage 2 and stage 3). After the screening visit and confirmation of eligibility, evaluable participants will be enrolled across treatment groups. In stage 1, up to 24 evaluable participants across two treatment groups will be enrolled. A Safety and Data Monitoring Committee will convene to review stage 1 data and decide whether further treatment groups are required in stage 2. Stage 2 will include participants across up to 3 treatment groups. Stage 3 will include two treatment groups:

Stage 1 Group 1: AZD9833 Dose A once daily Group 2: AZD9833 Dose B once daily

Stage 2 Group 1: AZD9833 Dose A once daily Group 2: AZD9833 Dose B once daily Group 3: AZD9833 Dose C once daily

Stage 3 Group 1: AZD9833 Dose A once daily Group 2: AZD9833 Dose B once daily

Adverse events and concomitant medications information will be collected throughout the study. Thereafter there will be 28-day follow-up visit after discontinuation of study treatment

This is a randomised, open-label, parallel-group study. The study is divided into three stages as follows:

1. Stage 1: In this stage post-menopausal participants will be randomised in 2 cohorts in 1:1 ratio to receive AZD9833 with 12 evaluable participants in each cohort.
2. Stage 2: In this stage post-menopausal participants may be randomised in up to 3 cohorts, which may include up to 3 doses of AZD9833.
3. Stage 3 : In this stage post-menopausal participants may be randomised in up to 2 cohorts in 1:1 ratio, which may include up to 2 doses of AZD9833.

A Study to Investigate the Biological Effects of AZD9833 in Women With ER-positive, HER2 Negative Primary Breast Cancer

A Randomised, Open-Label, Parallel-Group, Pre-surgical Study to Investigate the Biological Effects of AZD9833 in Women With ER-positive, HER2-negative Primary Breast Cancer (SERENA-3)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

To explore the ER pharmacodynamic (PD) effects of AZD9833 between pre- and on-treatment tumour samples in women with early breast cancer after AZD9833 treatment.

To explore the PgR PD effects of AZD9833 between pre- and on-treatment tumour samples in women with early breast cancer after AZD9833.

To explore the Ki-67 PD effects of AZD9833 between pre- and on-treatment tumour samples in women with early breast cancer after AZD9833.

Safety and tolerability will be assessed through the incidence of AEs.

To evaluate the PK of AZD9833 in this participant population.

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

Gastrointestinal Agents

Anticoagulants

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Anti-Infective Agents

Amino Acids

Midazolam

Omeprazole

Dabigatran

Celecoxib

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase 2 Inhibitors

Cyclooxygenase Inhibitors

Antacids

Anti-Ulcer Agents

Proton Pump Inhibitors

Antithrombins

Antithrombin III

Protease Inhibitors

Serine Proteinase Inhibitors

HIV Protease Inhibitors

Serine

Participants will receive single oral doses of midazolam and omeprazole together (Day 1 of Treatment Periods 1 and 3) and repeated doses of AZD9833 (Days 1 to 5 of Treatment Period 2 and Day 1 of Treatment Period 3)

Participants will receive single oral doses of dabigatran etexilate (Day 1 of Treatment Periods 1 and 2) and single oral dose of AZD9833 (Day 1 of Treatment Period 2)

Participants will receive single oral doses of celecoxib (Day 1 of Treatment Periods 1 and 3) and repeated oral doses of AZD9833 (Days 1 to 5 of Treatment Period 2 and Day 1 of Treatment Period 3)

AZD9833 tablets will be administered orally once daily on Days 1 - Day 5 (Treatment Period 2) and Day 1 (Treatment Period 3) for participants recruited to Arms A and C and Day 1 for those in Arm B

Midazolam will be administered orally as a syrup once on Day 1 of Treatment Periods 1 and 3; administered together with Omeprazole

An Omeprazole capsule will be administered once on Day 1 of Treatment Periods 1 and 3; administered together with Midazolam

A Dabigatran Etexilate capsule will be administered once on Day 1 of Treatment Periods 1 and 2

Dabigatran Etexilate

A Celecoxib capsule will be administered once on Day 1 of Treatment Periods 1 and 3

This study will be a fixed sequence drug-drug interaction study in healthy postmenopausal females, conducted at multiple study sites

Participants will be randomized to one of 3 treatment arms on Day 1 prior to Investigational Medicinal Product (IMP) administration:

* Arm A: single oral doses of midazolam and omeprazole administered together + repeated doses of AZD9833 .
* Arm B: single oral doses of dabigatran etexilate + single oral dose of AZD9833 .
* Arm C: single oral doses of celecoxib + repeated oral doses of AZD9833.

Each participant will be involved in the study for up to 7 to 8 weeks

Study to Assess the Effect of Co-Administration of AZD9833 on the Pharmacokinetics of Midazolam, of Omeprazole, of Celecoxib and of Dabigatran Etexilate in Healthy Postmenopausal Female Volunteers

A Phase 1, Multi-center, Open-label, 3-arm, Fixed Sequence Study to Assess the Effect of Co-administration of AZD9833 on the Pharmacokinetics of Midazolam (CYP3A4/5 Substrate), of Omeprazole (CYP2C19 Substrate), of Celecoxib (CYP2C9 Substrate) and of Dabigatran Etexilate (P-gp Transporter Substrate) in Healthy Postmenopausal Female Volunteers

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.

The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic (PK) variables of: - single-dose midazolam and omeprazole, administered together

* single-dose dabigatran etexilate
* single-dose celecoxib

The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic variables of:

* single-dose midazolam and omeprazole, administered together
* single-dose dabigatran etexilate
* single-dose celecoxib

The effects of AZD9833 will be evaluated in healthy postmenopausal female participants on the key pharmacokinetic variables of:

* single-dose midazolam and omeprazole administered together
* single-dose dabigatran etexilate
* single-dose celecoxib

The safety and tolerability of AZD9833, alone and in combination with midazolam, omeprazole, dabigatran etexilate, and celecoxib will be evaluated in healthy postmenopausal female participants.

AZD9833 PK and the effect of AZD9833 on the PK of dabigatran etexilate will be further characterized.

AZD9833 PK and the effect of AZD9833 on the PK of dabigatran etexilate, and will be further characterized.

AZD9833 PK and the effect of AZD9833 on the PK of dabigatran etexilate will be further characterized

AZD9833 PK and the effect of AZD9833 on the PK of midazolam, omeprazole, dabigatran etexilate, and celecoxib will be further characterized.

Menopause

Fulvestrant

The patients will receive AZD9833 (Dose A).

The patients will receive AZD9833 (Dose B).

The patients will receive AZD9833 (Dose C).

The patients will receive Fulvestrant (500 mg).

Dosage formulation: AZD9833 tablets will be administered orally.

Dosage formulation: Fulvestrant will be administered via intramuscular (IM) injection.

This study is randomized, open-label, parallel-group, multicentre Phase 2 study aimed to compare the efficacy and safety of oral AZD9833 versus intramuscular (IM) fulvestrant in women with advanced breast cancer.

Post-menopausal women with histologically or cytologically confirmed metastatic or loco-regionally recurrent ER-positive HER2-negative breast cancer before randomization and fulfilling all of the inclusion criteria and none of the exclusion criteria will be included.

After the screening visit and confirmation of eligibility, patients will be randomly assigned in a 1:1:1:1 ratio to receive 1 of the following 4 treatments, consisting of 4-week treatment cycles until disease progression (assessed by the Investigator as defined by Response Evaluation Criteria in Solid Tumours \[RECIST\] version 1.1):

* AZD9833 (Dose A)
* AZD9833 (Dose B)
* AZD9833 (Dose C)
* Fulvestrant (500 mg) During the treatment period, patients will have scheduled visits until treatment discontinuation. After the end of treatment, patients will attend 2 safety follow-up visits (at the time of treatment discontinuation and 28 days later) and will continue to be followed for survival.

As of December 2020, the Sponsor stopped enrolment to Dose C.

A Study to Investigate Efficacy and Safety With Oral AZD9833 Compared With Intramuscular Fulvestrant in Post-menopausal Women at Least 18 Years of Age With Advanced ER-positive HER2 Negative Breast Cancer

SERENA-2: A Randomised, Open-Label, Parallel-Group, Multicentre Phase 2 Study Comparing the Efficacy and Safety of Oral AZD9833 Versus Fulvestrant in Women With Advanced ER-Positive HER2-Negative Breast Cancer

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

The safety and tolerability of AZD9833 when compared to fulvestrant in women with advanced ER-positive HER2-negative breast cancer was evaluated.

PFS was assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1. PFS was defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or received another anti-cancer therapy prior to progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.

Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

ORR was assessed by the Investigator as defined by RECIST version 1.1. The ORR was defined as investigator assessed Complete Response or Partial Response prior to progression in patients with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).

Adjusted response rate was presented in this analysis.

Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

DoR was assessed by the Investigator as defined by RECIST version 1.1. The DoR was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.

The percentage change in tumour size at 16 weeks was obtained for each patient, based on RECIST measurements taken at baseline and at 16 weeks. Tumour size is the sum of the longest diameters of the target lesions (TLs). Percentage change in the sum of longest TLs diameters at 16 weeks was measured.

The OS was defined as the time from randomisation to death due to any cause.

Clinical benefit rate was defined as patients with best objective response of complete response or partial response in the first 25 weeks or who have stable disease for at least 23 weeks after randomization.

Adjusted response rate was presented in this analysis.

Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

The plasma concentrations of AZD9833 at steady state were evaluated.

The pharmacodynamics of AZD9833 and fulvestrant in a subgroup of patients.

To evaluate the effect of AZD9833 and fulvestrant on the patients' health-related quality of life, as assessed by patient completed HRQoL questionnaires.

The patients received AZD9833 75mg oral tablets once daily.

AZD9833 75mg

The patients received AZD9833 150mg oral tablets once daily.

AZD9833 150mg

The patients received AZD9833 300mg oral tablets once daily.

AZD9833 300mg

The patients received Fulvestrant 500 mg via IM injection.

Fulvestrant 500 mg

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Full Analysis Set (FAS) consisted of all randomised patients, with treatment groups assigned in accordance with the randomisation, regardless of the actual treatment received.

At the time of CSR finalization, CSP version 5.0 was available, therefore, CSP version 5.0 was redacted and submitted along with the Results Registration Form.

Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

Global Clinical Lead

FAS consisted of all randomised patients, with treatment groups assigned in accordance with the randomisation, regardless of the actual treatment received.

Progression-free Survival (PFS)

A subset of the FAS with measurable disease.

Objective Response Rate (ORR)

Duration of Response (DoR)

Percentage Change in Tumour Size at 16 Weeks

Overall Survival (OS)

Clinical Benefit Rate at 24 Weeks (CBR24)

Cycle 1 Day 15 (pre-dose)

Cycle 1 Day 15 (2h)

The PK Analysis Set consisted of all patients who received at least one dose of AZD9833 per protocol, for whom there is at least one reportable PK concentration.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)	NCT04964934	ER-Positive HER...	AZD9833 AZD9833 Placebo Anastrozole Anastrozole pla... Letrozole Letrozole place... Palbociclib Abemaciclib Luteinizing hor... Ribociclib	18 Years - 130 Years	AstraZeneca
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	ER-Positive HER...	AZD9833 Anastrozole Anastrozole pla... AZD9833 placebo Palbociclib Luteinizing hor...	18 Years - 130 Years	AstraZeneca
A Study to Investigate the Biological Effects of AZD9833 in Women With ER-positive, HER2 Negative Primary Breast Cancer	NCT04588298	HER2-negative B...	AZD9833	18 Years - 130 Years	AstraZeneca
Study to Assess the Effect of Co-Administration of AZD9833 on the Pharmacokinetics of Midazolam, of Omeprazole, of Celecoxib and of Dabigatran Etexilate in Healthy Postmenopausal Female Volunteers	NCT05438303	Healthy Volunte...	AZD9833 Midazolam Omeprazole Dabigatran Etex... Celecoxib	50 Years - 70 Years	AstraZeneca
Study to Assess the Effect of Co-Administration of AZD9833 on the Pharmacokinetics of Midazolam, of Omeprazole, of Celecoxib and of Dabigatran Etexilate in Healthy Postmenopausal Female Volunteers	NCT05438303	Healthy Volunte...	AZD9833 Midazolam Omeprazole Dabigatran Etex... Celecoxib	50 Years - 70 Years	AstraZeneca
A Study to Investigate Efficacy and Safety With Oral AZD9833 Compared With Intramuscular Fulvestrant in Post-menopausal Women at Least 18 Years of Age With Advanced ER-positive HER2 Negative Breast Cancer	NCT04214288	Advanced ER-Pos...	AZD9833 Fulvestrant	18 Years - 130 Years	AstraZeneca
Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6)	NCT04964934	ER-Positive HER...	AZD9833 AZD9833 Placebo Anastrozole Anastrozole pla... Letrozole Letrozole place... Palbociclib Abemaciclib Luteinizing hor... Ribociclib	18 Years - 130 Years	AstraZeneca
AZD9833 China PK Study	NCT04818632	ER+, HER2-, Met...	AZD9833 AZD9833 AZD9833 with pa... AZD9833 with ev...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for azd9833

Every month we try and update this database with for azd9833 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for azd9833

Every month we try and update this database with for azd9833 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for azd9833 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.