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Clinical Trials List

Protocol NumberD8532C00001
Active

2021-03-16 - 2029-12-31

Phase III

Recruiting9

Terminated1

ICD-10C50.911

Malignant neoplasm of unspecified site of right female breast

ICD-10C50.912

Malignant neoplasm of unspecified site of left female breast

ICD-10C50.919

Malignant neoplasm of unspecified site of unspecified female breast

ICD-10Z51.12

Encounter for antineoplastic immunotherapy

ICD-9174.9

Malignant neoplasm of female breast, unspecified

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

  • Trial Applicant

  • Sponsor

    AstraZeneca

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2026/02/01

Investigators and Locations

Principal Investigator HWEI-CHUNG WANG Division of General Surgery
China Medical University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator TSU-YI CHAO Division of Hematology & Oncology
Taipei Medical University-Shuang Ho Hospital,Ministry of Health and Welfare

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Jia-Ruey Tsai Division of Hematology & Oncology
Taipei Medical University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator YEN-SHEN LU Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator 張源清 Division of General Surgery
MacKay Memorial Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Shin-Cheh Chen Division of General Surgery
Linkou Chang Gung Medical Foundation

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Wei-Pang Chung Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator 饒坤銘 Division of Hematology & Oncology
E-DA Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator 劉建廷 Division of Hematology & Oncology
Kaoshiung Chang Gung Memorial Hospital of the C.G.M.F.

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Chih-Chiang Hung Division of General Surgery
Taichung Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Stop recruiting

Condition/Disease

AZD9833 AZD9833 is being developed for treatment of ER-positive, HER2-negative breast cancer. Anastrozole Arimidex is indicated for the: -Treatment of hormone receptor-positive advanced breast cancer in postmenopausal women. -Adjuvant treatment of hormone receptor-positive early invasive breast cancer in postmenopausal women. -Adjuvant treatment of hormone receptor-positive early invasive breast cancer in postmenopausal women who have received 2 to 3 years of adjuvant tamoxifen. Palbociclib IBRANCE is indicated for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer: -in combination with an aromatase inhibitor; -in combination with fulvestrant in women who have received prior endocrine therapy (see section 5.1). In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinizing hormone-releasing hormone (LHRH) agonist.

Objectives

Primary Objectives: 1. To demonstrate superiority of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of PFS in the Full Analysis Set (FAS). Secondary Objectives: 1. To demonstrate superiority of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of OS in the FAS. 2. To demonstrate superiority of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of second progression free survival (PFS2) in the FAS.  3. To estimate the effectiveness of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of ORR in the FAS.   4. To estimate the effectiveness of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of DoR in the FAS.   5. To estimate the effectiveness of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of the clinical benefit rate at 24 weeks (CBR24) in the FAS. 6. To estimate the effectiveness of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of time to chemotherapy in the FAS. 7. To estimate the effectiveness of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of time to first subsequent therapy or death (TFST) in the FAS. 8. To estimate the effectiveness of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of time to second subsequent therapy or death (TSST) in the FAS. 9. 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. To assess symptoms, functioning, and healthrelated quality of life in participants treated with AZD9833 plus palbociclib compared with anastrozole plus palbociclib using the EORTC QLQ-C30 and EORTC QLQ-BR45 questionnaires in the FAS.

Test Drug

AZD9833
ArimidexR
IbranceR

Active Ingredient

AZD9833
Anastrozole
Palbociclib

Dosage Form

Tablet
Capsule

Dosage

25 mg、75 mg
1 mg
75mg、100 mg、125 mg

Endpoints

PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause.

Inclution Criteria

Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Informed Consent
1 Capable of giving signed informed consent, which includes compliance with the require-ments and restrictions listed in the ICF and in this protocol.
2 Evidence of a personally signed and dated informed consent document indicating that the participant (or legal representative) has been informed of all pertinent aspects of the study before any study-specific activity is performed.
3 Provision of signed and dated written Optional Genetic Research Information informed con-sent prior to collection of sample for optional genetic research that supports Genomic Initia-tive (as allowed per local regulations).
Age and Sex
4 Female or male, ≥ 18 years at the time of screening. For patients aged < 20 years and en-rolled in Japan, a written informed consent should be obtained from the participant and his/her legally acceptable representative.
Type of Participant and Disease Characteristics
5 Histologically or cytologically documented diagnosis of ER+, HER2-negative breast cancer based on local laboratory results and who are not amenable to resection or radiation therapy with curative intent.
(a) Documentation of ER+ tumour (> 10% positive stained cells) irrespective of PgR sta-tus, based on most recent tumour biopsy in the recurrent or metastatic setting (unless bone-only disease or if the tissue could not be obtained, see below) utilising an assay consistent with ASCO CAP 2020 guidelines.
(b) Documented HER2-negative tumour based on local testing on most recent tumour bi-opsy: HER2-negative tumour is determined as IHC score 0/1+ or negative by in situ hybridisation (FISH/CISH/SISH/DISH) defined as a HER2/CEP17 ratio < 2 or for single probe assessment a HER2 copy number < 4, consistent with ASCO CAP 2018 guidelines.
6 Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent or metastatic ER+ disease.
7 Patients must have:
(a) at least one lesion, not previously irradiated, that can be measured accurately at base-line as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with CT or MRI which is suitable for accurate repeated measurements.
(b) OR, in absence of measurable disease as defined above, at least one lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI; patients with scle-rotic/osteoblastic bone lesions only in the absence of measurable disease are not eligi-ble.
8 De novo Stage 4 disease, or recurrence from early stage disease after standard adjuvant en-docrine therapy meeting either one of the following criteria:
(a) Received at least 24 months of AI treatment as part of their adjuvant therapy without disease progression and relapsed > 1 year after the end of AI (applicable to male, pre/peri and post-menopausal women).
(b) Received at least 24 months of tamoxifen treatment as part of their adjuvant endocrine therapy if participant is male or premenopausal or peri-menopausal female at study en-try. Note that a 4-week washout period is required after the last dose of tamoxifen pri-or to randomisation.
9 Eastern Cooperative Oncology Group performance status of 0 or 1.
10 Adequate organ and marrow function defined as follows:
(a) Absolute Neutrophil Count ≥ 1500/ mm3 (1.5 × 109/ L)
(b) Platelets ≥ 100000/ mm3 (100 × 109/ L)
(c) Haemoglobin ≥ 9 g/dL (90 g/ L)
(d) Serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 30 mL/min as cal-culated using the Cockcroft-Gault equation.
(e) Total serum bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN if Gilbert’s disease [unconjugated hyperbilirubinemia])
(f) Aspartate aminotransferase and/or ALT ≤ 3.0 × ULN (≤ 5.0 × ULN if liver metastases present)
(g) Alkaline phosphatase ≤ 2.5 × ULN (≤ 5.0 × ULN if bone or liver metastases present)
11 Minimum body weight of 35 kg.
Reproduction
12. Female or male participants who are not abstinent (in line with their preferred and usual life-style choice), and intend to be heterosexually active with a partner. Female participants must be using highly effective contraceptive measures, and must have a negative pregnancy test before first dose of any study treatment if they are of childbearing potential; or must have ev-idence of non-child-bearing potential by fulfilling one of the following criteria at screening:
 Post-menopausal, defined as women:
o Age ≥ 60 years
o Age < 60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estra-diol and FSH level within the laboratory’s reference range for post menopausal females
o Previous bilateral surgical oophorectomy
o Medically confirmed ovarian failure
OR
 Pre/peri-menopausal, ie, not meeting the criteria for being post-menopausal.
o Pre-/peri-menopausal women can be enrolled if amenable to be treated with monthly LHRH agonists (goserelin or leuprorelin). Participants must have con-comitant treatment with LHRH agonists (goserelin or leuprorelin) – which must have been started 3 weeks before Cycle 1 Day 1 - and must be willing to contin-ue on it for the duration of the study.
13. Male participants can be enrolled if amenable to be treated with monthly LHRH agonists (goserelin or leuprorelin) unless the participants have clear orchiectomy medical history.
14. Willingness to use 2 non-hormonal based methods of contraception throughout the study.
Tumour Sample Requirements
15 All participants must agree to provide and have available a FFPE tissue biopsy sample tak-en at the time of presentation with recurrent or metastatic disease. A de novo biopsy is re-quired if no archived tissue taken at the time of presentation with recurrent/metastatic dis-ease is available. In the exceptional circumstance of bone-only disease, archived primary breast cancer specimen may be submitted. This also applies if tissue could not be obtained (eg, inaccessible or participant safety concern), after discussion with the AstraZeneca Study Physician.
16 All participants must agree to provide tumour tissues for centralised retrospective confirma-tion of ER status and to evaluate correlation between genes, proteins, and RNAs relevant to the ER pathways and sensitivity/resistance to the investigational agents.
Other
17 Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria

Exclusion Criteria
Participants are excluded from participating in the study if any of the following criteria apply:
Medical Conditions
1 Have advanced, symptomatic, visceral spread, that are at risk of life-threatening complica-tions in the short term (including participants with massive uncontrolled effusions [pleural, pericardial, peritoneal]) and pulmonary lymphangitis).
2 Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral oedema, and/or progres-sive growth. Participants with a history of brain or other CNS metastases or cord compres-sion are eligible if they have been definitively treated with local therapy (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomisation.
3 History of another primary malignancy except for the following:
• Malignancy treated with curative intent with no known active disease ≥ 3 years be-fore the first dose of study treatment, and of very low potential risk for recurrence.
• Adequately treated non-melanoma skin cancer or lentigo malignancy without evi-dence of disease.
• Other exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has undergone potentially curative therapy.
4 As judged by the investigator, any evidence of diseases (such as severe or uncontrolled sys-temic diseases, including uncontrolled hypertension, 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 jeopardise compliance with the protocol.
5 Active primary immunodeficiency, known HIV infection, or active hepatitis B or C infec-tion. Patients positive for hepatitis B or C antibody are eligible only if polymerase chain re-action is negative for HCB or HCV RNA, respectively. Participants should be tested for HIV prior to randomization if required by local regulations or by the IRB/IEC.
6 Persistent toxicities (CTCAE Grade > 2) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacer-bated by study treatment may be included (eg, hearing loss) after consultation with the AstraZeneca study physician.
7 Mean resting QTcF > 480 msec based on the mean value of the triplicate ECGs.
8 Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including serum/plasma potassium*, magnesium* and calcium* below the LLN, heart failure, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointe. * Correction of electrolyte abnormalities to within normal ranges can be performed during screening
9 Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (eg, complete left bundle branch block, second- and third-degree heart block), or clin-ically significant sinus pause. Patients with pacemakers may be enrolled.
10 Resting heart rate < 60 bpm.
11 Left ventricular ejection fraction < 50% and/or experience of any of the following proce-dures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure New York Heart Association Grade ≥ 2, cerebrovascular accident, or transient ischaemic attack.
12 Blood pressure systolic > 160 and diastolic > 90 mg Hg. Participants with hypertension ad-equately controlled at baseline may be enrolled into the study.
13 Symptomatic hypotension or asymptomatic hypotension with systolic blood pressure < 90 mm Hg.
14 Best correct visual acuity in the worst seeing eye worse than 20/100 (Snellen equivalent). Participants with vision worse than 20/100 due to a treatable condition (eg, cataract) may be discussed with the Sponsor study team and considered on an individual base basis.
15 Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant gastric/bowel resection that would preclude ad-equate absorption, distribution, metabolism, or excretion of AZ9833, palbociclib, or anas-trozole.
16 Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
Prior/Concomitant Therapy
17 Previous neoadjuvant or adjuvant treatment with a AI treatment +/- CDK4/6 inhibitor with disease recurrence while on or within 12 months of completing treatment.
18 Any concurrent anti-cancer treatment.
19 Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks before the first dose of study treatment.
20 Participants treated:
(a) Within the last 2 weeks before randomisation with medications or herbal supplements known to be strong inhibitors/inducers of CYP3A4/5, sensitive CYP2B6 substrates and drugs which are substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index ie, warfarin (and other coumarin-derived vitamin K antagonist anti-coagulants) and phenytoin.
(b) Within the timeframe indicated with drugs that are known to prolong the QT interval and have a known risk of TdP.
(c) Regarding medications that are known to reduce sinus heart rate.
21 Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study treatment or an anticipated need for major surgery and/or any surgery requiring general anaesthesia during the study.
22 Previous treatment with AZD9833.
Prior/Concurrent Clinical Study Experience
23 Participation in another clinical study with a study treatment or investigational medicinal device administered in the last 4 weeks prior to randomisation or concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or dur-ing the follow-up period of an interventional study.
Other Exclusions
24 Known hypersensitivity to anastrozole, or any of its excipients, or history of hypersensitivi-ty to active or inactive excipients of AZD9833/placebo or drugs with a similar chemical structure or class to AZD9833 or known hypersensitivity to palbociclib and its excipients.
25 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
26 Judgment by the investigator that the participant should not participate in the study if they are unlikely to comply with study procedures, restrictions, and requirements.

The Estimated Number of Participants

  • Taiwan

    65 participants

  • Global

    1342 participants

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