Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer.

NCT ID: NCT03616587

Last Updated: 2026-01-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 396 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-11
• Study Completion Date: 2027-06-24

Brief Summary

A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination in Women with ER Positive, HER2 Negative Advanced Breast Cancer (SERENA-1)

Detailed Description

This is a multicentre dose escalation and expansion, first-in-human study designed to evaluate the safety and tolerability of AZD9833, alone (Parts A and B), or in combination with palbociclib (Parts C and D), or in combination with everolimus (Parts E and F), or in combination with abemaciclib (± anastrozole) (Parts G and H), or in combination with capivasertib (Parts I and J), or in combination with ribociclib (± anastrozole) (Parts K and L), or in combination with anastrozole (Parts M and N) in women with endocrine-resistant ER+ HER2- breast cancer that is not amenable to treatment with curative intent.

Conditions

ER+ HER2- Advanced Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AZD9833 monotherapy dose escalation

Group Type: EXPERIMENTAL

AZD9833

Intervention Type: DRUG

Part A: AZD9833 monotherapy dose escalation.

AZD9833 monotherapy dose expansion

Group Type: EXPERIMENTAL

AZD9833

Intervention Type: DRUG

Part B: AZD9833 monotherapy expansion.

AZD9833 with palbociclib dose escalation

Group Type: EXPERIMENTAL

AZD9833 with palbociclib

Intervention Type: DRUG

Part C: AZD9833 in combination with palbociclib dose escalation

AZD9833 with palbociclib dose expansion

Group Type: EXPERIMENTAL

AZD9833 with palbociclib

Intervention Type: DRUG

Part D: AZD9833 in combination with palbociclib expansion

AZD9833 with everolimus dose expansion

Group Type: EXPERIMENTAL

AZD9833 with everolimus

Intervention Type: DRUG

Part F: AZD9833 in combination with everolimus dose expansion

AZD9833 with everolimus dose escalation

Group Type: EXPERIMENTAL

AZD9833 with everolimus

Intervention Type: DRUG

Part E: AZD9833 in combination with everolimus dose escalation

AZD9833 with abemaciclib (± anastrozole) dose escalation

Group Type: EXPERIMENTAL

AZD9833 with abemaciclib

Intervention Type: DRUG

Part G: AZD9833 in combination with abemaciclib (± anastrozole) dose escalation

AZD9833 with abemaciclib (± anastrozole)dose expansion

Group Type: EXPERIMENTAL

AZD9833 with abemaciclib

Intervention Type: DRUG

Part H: AZD9833 in combination with abemaciclib (± anastrozole) dose expansion

AZD9833 with capivasertib dose escalation

Group Type: EXPERIMENTAL

AZD9833 with capivasertib

Intervention Type: DRUG

Part I: AZD9833 in combination with capivasertib dose escalation

AZD9833 with capivasertib dose expansion

Group Type: EXPERIMENTAL

AZD9833 with capivasertib

Intervention Type: DRUG

Part J: AZD9833 in combination with capivasertib dose expansion

AZD9833 with ribociclib (± anastrozole) dose escalation

Group Type: EXPERIMENTAL

AZD9833 with ribociclib

Intervention Type: DRUG

Part K: AZD9833 in combination with ribociclib (± anastrozole) dose escalation

AZD9833 with ribociclib (± anastrozole) dose expansion

Group Type: EXPERIMENTAL

AZD9833 with ribociclib

Intervention Type: DRUG

Part L: AZD9833 in combination with ribociclib (± anastrozole) dose expansion

AZD9833 with anastrozole dose escalation

Group Type: EXPERIMENTAL

AZD9833 with anastrozole

Intervention Type: DRUG

Part M: AZD9833 in combination with anastrozole dose escalation

AZD9833 with anastrozole dose expansion

Group Type: EXPERIMENTAL

AZD9833 with anastrozole

Intervention Type: DRUG

Part N: AZD9833 in combination with anastrozole dose expansion

Interventions

AZD9833

Part A: AZD9833 monotherapy dose escalation.

Intervention Type: DRUG

AZD9833

Part B: AZD9833 monotherapy expansion.

Intervention Type: DRUG

AZD9833 with palbociclib

Part C: AZD9833 in combination with palbociclib dose escalation

Intervention Type: DRUG

AZD9833 with palbociclib

Part D: AZD9833 in combination with palbociclib expansion

Intervention Type: DRUG

AZD9833 with everolimus

Part E: AZD9833 in combination with everolimus dose escalation

Intervention Type: DRUG

AZD9833 with everolimus

Part F: AZD9833 in combination with everolimus dose expansion

Intervention Type: DRUG

AZD9833 with abemaciclib

Part G: AZD9833 in combination with abemaciclib (± anastrozole) dose escalation

Intervention Type: DRUG

AZD9833 with abemaciclib

Part H: AZD9833 in combination with abemaciclib (± anastrozole) dose expansion

Intervention Type: DRUG

AZD9833 with capivasertib

Part I: AZD9833 in combination with capivasertib dose escalation

Intervention Type: DRUG

AZD9833 with capivasertib

Part J: AZD9833 in combination with capivasertib dose expansion

Intervention Type: DRUG

AZD9833 with ribociclib

Part K: AZD9833 in combination with ribociclib (± anastrozole) dose escalation

Intervention Type: DRUG

AZD9833 with ribociclib

Part L: AZD9833 in combination with ribociclib (± anastrozole) dose expansion

Intervention Type: DRUG

AZD9833 with anastrozole

Part M: AZD9833 in combination with anastrozole dose escalation

Intervention Type: DRUG

AZD9833 with anastrozole

Part N: AZD9833 in combination with anastrozole dose expansion

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Signed written informed consent.

2. >= 18 years

3. Any menopausal status:

1. Pre-menopausal women must have commenced treatment with an LHRH agonist at least 4 weeks prior to starting AZD9833 (± combination IMP(s)) and must be willing to continue to receive LHRH agonist therapy for the duration of the study

2. Post-menopausal defined according to standard criteria in the protocol.

4. Histological or cytological confirmation of adenocarcinoma of the breast

5. Documented positive oestrogen receptor status of primary or metastatic tumour tissue, according to the local laboratory parameters.HER-2 negative.

6. Metastatic disease or locoregionally recurrent disease which is refractory or intolerant to existing therapy(ies) known to provide clinical benefit

7. Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting IMP

8. Prior chemotherapy, endocrine therapy and other therapy as follows:

1. No more than 2 lines of chemotherapy for advanced disease

2. Recurrence or progression on at least one line of endocrine therapy in the advanced/metastatic disease setting

3. There is no limit on the number of lines of prior endocrine therapies

4. Prior treatment with CDK4/6 inhibitors is permitted

9. Women of childbearing potential must agree to use a highly effective contraceptive measure, must not be breast feeding, and must have a negative pregnancy test prior to the start of dosing.

10. At least one lesion (measurable and/or non-measurable, as per RECIST 1.1 that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI, or plain X-ray; or clinical examination. Blastic-only lesions in bone are not considered assessable.

12. Disease suitable for paired baseline and on-study tumour biopsies

13. Washout from prior fulvestrant: 6 months

14. Washout from prior tamoxifen: 4 months

15. Signed written informed consent for tumour biopsies

Exclusion Criteria

1. Intervention with any of the following

1. Any cytotoxic chemotherapy, investigational agents/other anti-cancer drugs for the treatment of advanced breast cancer from a previous treatment regimen or clinical study within 14 days of the first dose of IMP

2. Concomitant medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 (CYP) 3A4/5, sensitive CYP2B6 substrates, and drugs which are sensitive substrates of CYP2C9 and/or CYP2C19, and which have a narrow therapeutic index. In addition: Parts E and F will exclude the concomitant use of moderate CYP3A4 and/or Pgp inhibitors; Parts G H, I, J, K and L will exclude the concomitant use of moderate CYP3A4/5 inhibitors and inducers; Parts I and J will exclude concomitant use of sensitive substrates of CYP3A4 and/or CYP2D6 with a narrow therapeutic index."

3. Drugs known to prolong QT and known risk of Torsades de Pointes

4. Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of IMP, except patients receiving radiotherapy to more than 30% of the bone marrow/a wide field of radiation within 4 weeks of the first dose of IMP

5. Major surgical procedure/significant traumatic injury, as judged by the investigator, within 4 weeks of the first dose of IMP, or an anticipated need for major surgery and/or any surgery requiring general anaesthesia during the study.

2. Any unresolved toxicities from prior therapy > CTCAE Grade 1 at the time of starting IMP, with the exception of alopecia.

3. Presence of life-threatening metastatic visceral disease, as judged by the investigator, uncontrolled CNS metastatic disease. Patients with spinal cord compression and/or brain metastases may be enrolled if definitively treated (eg, surgery or radiotherapy) and stable off steroids for at least 4 weeks prior to start of IMP

4. Past medical history of ILD (Parts E, F, K and L only)

5. Currently symptomatic radiotherapy-induced pneumonitis (Parts E, F, K and L only)

6. Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV)

7. Any of the following cardiac criteria

1. Mean resting QTcF >470 msec obtained from a triplicate ECG (≥450 msec for Parts K and L)

2. 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 clinically significant sinus pause. Patients with controlled atrial fibrillation can be enrolled c) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as symptomatic heart failure, hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome, or unexplained sudden death at <40 years of age. Hypertrophic cardiomyopathy and clinically significant stenotic valve disease

(d) LVEF <50% and/or experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure NYHA Grade ≥2, cerebrovascular accident, or transient ischaemic attack.

(e) Uncontrolled hypertension. Hypertensive patients may be eligible but blood pressure must be adequately controlled at baseline.

(f) Uncontrolled hypotension - SBP <90 mmHg and/or DBP <50 mmHg for parts I &J

8. Inadequate bone marrow reserve/organ function as demonstrated by any of the following lab values

1. ANC <1.5 × 109/L

2. Platelet count <100 × 109/L

3. Haemoglobin <90 g/L

4. ALT >2.5 × ULN

5. AST >2.5 × ULN

6. TBL >1.5 × ULN or >3 × ULN in the presence of documented Gilbert's Syndrome

7. GFR <50 mL/min

9. Clinically significant abnormalities of glucose metabolism, as defined by any of the following at screening (Parts I and J only):

1. Patients with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment.

2. HbA1c ≥8.0% (63.9 mmol/mol).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Baird, MD PhD FRCP

Role: PRINCIPAL_INVESTIGATOR

Breast Cancer Research Unit, University of Cambridge

Justin Lindemann, MBChB MBA

Role: STUDY_DIRECTOR

AstraZeneca

Locations

Research Site

Aurora, Colorado, United States

Research Site

Sarasota, Florida, United States

Research Site

Philadelphia, Pennsylvania, United States

Research Site

Nashville, Tennessee, United States

Research Site

Salt Lake City, Utah, United States

Research Site

Barcelona, , Spain

Research Site

Barcelona, , Spain

Research Site

Madrid, , Spain

Research Site

Madrid, , Spain

Research Site

Seville, , Spain

Research Site

Valencia, , Spain

Research Site

Cambridge, , United Kingdom

Research Site

Leeds, , United Kingdom

Research Site

London, , United Kingdom

Research Site

Manchester, , United Kingdom

Research Site

Sutton, , United Kingdom

Research Site

Sutton, , United Kingdom

Countries

United States; Spain; United Kingdom

Related Links

https://breastcancerstudylocator.com/

Related Info

Other Identifiers

138396

Identifier Type: REGISTRY

Identifier Source: secondary_id

2023-506890-37-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-000667-92

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D8530C00001

Identifier Type: -

Identifier Source: org_study_id