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ER+ HER2- Advanced Breast CancerPhase 1SERENA-1NCT03616587

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

A Phase 1 study testing AZD9833, AZD9833 with palbociclib and AZD9833 with everolimus in people with ER+ HER2- Advanced Breast Cancer, run by AstraZeneca at 17 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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) Read more about this study

Who is it for?
Ages 18 to 130 years, women only
Conditions the study is for
ER+ HER2- Advanced Breast Cancer
What is being tested?
AZD9833, AZD9833 with palbociclib and AZD9833 with everolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
396 participants
Where
17 sitesin 3 countries
Study dates
11 Oct 2018to 24 Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 130 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent.
  • >= 18 years
  • Any menopausal status:
  • 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
  • Post-menopausal defined according to standard criteria in the protocol.
  • Histological or cytological confirmation of adenocarcinoma of the breast
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  • Documented positive oestrogen receptor status of primary or metastatic tumour tissue, according to the local laboratory parameters.HER-2 negative.
  • Metastatic disease or locoregionally recurrent disease which is refractory or intolerant to existing therapy(ies) known to provide clinical benefit
  • Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting IMP
  • Prior chemotherapy, endocrine therapy and other therapy as follows:
  • No more than 2 lines of chemotherapy for advanced disease
  • Recurrence or progression on at least one line of endocrine therapy in the advanced/metastatic disease setting
  • There is no limit on the number of lines of prior endocrine therapies
  • Prior treatment with CDK4/6 inhibitors is permitted
  • 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.
  • 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.
  • ECOG/ WHO performance status 0 to 1, with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks Inclusion criteria for the paired tumour biopsy research:
  • Disease suitable for paired baseline and on-study tumour biopsies
  • Washout from prior fulvestrant: 6 months
  • Washout from prior tamoxifen: 4 months
  • Signed written informed consent for tumour biopsies

Who cannot join

  • Intervention with any of the following
  • 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
  • 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."
  • Drugs known to prolong QT and known risk of Torsades de Pointes
  • 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
  • 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.
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  • Any unresolved toxicities from prior therapy > CTCAE Grade 1 at the time of starting IMP, with the exception of alopecia.
  • 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
  • Past medical history of ILD (Parts E, F, K and L only)
  • Currently symptomatic radiotherapy-induced pneumonitis (Parts E, F, K and L only)
  • 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)
  • Any of the following cardiac criteria
  • Mean resting QTcF >470 msec obtained from a triplicate ECG (≥450 msec for Parts K and L)
  • 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
  • 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.
  • Uncontrolled hypertension. Hypertensive patients may be eligible but blood pressure must be adequately controlled at baseline.
  • Uncontrolled hypotension - SBP <90 mmHg and/or DBP <50 mmHg for parts I \&J
  • Inadequate bone marrow reserve/organ function as demonstrated by any of the following lab values
  • ANC <1.5 × 109/L
  • Platelet count <100 × 109/L
  • Haemoglobin <90 g/L
  • ALT >2.5 × ULN
  • AST >2.5 × ULN
  • TBL >1.5 × ULN or >3 × ULN in the presence of documented Gilbert's Syndrome
  • GFR <50 mL/min
  • Clinically significant abnormalities of glucose metabolism, as defined by any of the following at screening (Parts I and J only):
  • Patients with diabetes mellitus type I or diabetes mellitus type II requiring insulin treatment.
  • HbA1c ≥8.0% (63.9 mmol/mol).

Trial locations and contacts

17 sites in 3 countries.

17 sites in 3 countries

Spain6 sites

  • Research Site

    Barcelona, 08035

  • Research Site

    Barcelona, 8036

  • Research Site

    Madrid, 28041

  • Research Site

    Madrid, 28050

  • Research Site

    Seville, 41013

  • Research Site

    Valencia, 46010

Other trials in Spain

United Kingdom6 sites

  • Research Site

    Cambridge, CB2 0QQ

  • Research Site

    Leeds, LS9 7TF

  • Research Site

    London, SW2 6JJ

  • Research Site

    Manchester, M20 4GJ

  • Research Site

    Sutton, SM1 2DL

  • Research Site

    Sutton, SM2 5PT

Other trials in United Kingdom

United States5 sites

  • Research Site

    Aurora, Colorado, 80045

  • Research Site

    Nashville, Tennessee, 37203

  • Research Site

    Philadelphia, Pennsylvania, 19111

  • Research Site

    Salt Lake City, Utah, 84112

  • Research Site

    Sarasota, Florida, 34232

Other trials in United States

About this study

Official title: 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)

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)

Read the 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.

Being tested
AZD9833, AZD9833 with palbociclib, AZD9833 with everolimus, AZD9833 with abemaciclib, AZD9833 with capivasertib
Keywords
Breast Cancer, Phase 1, Safety, Tolerability, Pharmacokinetics, ER Positive, HER2 Negative, Advanced Breast Cancer, Camizestrant
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD9833Drug

    Part A: AZD9833 monotherapy dose escalation.

  • AZD9833Drug

    Part B: AZD9833 monotherapy expansion.

  • AZD9833 with palbociclibDrug

    Part C: AZD9833 in combination with palbociclib dose escalation

  • AZD9833 with palbociclibDrug

    Part D: AZD9833 in combination with palbociclib expansion

  • AZD9833 with everolimusDrug

    Part E: AZD9833 in combination with everolimus dose escalation

  • AZD9833 with everolimusDrug

    Part F: AZD9833 in combination with everolimus dose expansion

  • AZD9833 with abemaciclibDrug

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

  • AZD9833 with abemaciclibDrug

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

  • AZD9833 with capivasertibDrug

    Part I: AZD9833 in combination with capivasertib dose escalation

  • AZD9833 with capivasertibDrug

    Part J: AZD9833 in combination with capivasertib dose expansion

  • AZD9833 with ribociclibDrug

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

  • AZD9833 with ribociclibDrug

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

  • AZD9833 with anastrozoleDrug

    Part M: AZD9833 in combination with anastrozole dose escalation

  • AZD9833 with anastrozoleDrug

    Part N: AZD9833 in combination with anastrozole dose expansion

Study groups in NCT03616587
Study groupRoleWhat they receive
AZD9833 monotherapy dose escalationExperimentalNot described
Receives: Drug: AZD9833
AZD9833 monotherapy dose expansionExperimentalNot described
Receives: Drug: AZD9833
AZD9833 with palbociclib dose escalationExperimentalNot described
Receives: Drug: AZD9833 with palbociclib
AZD9833 with palbociclib dose expansionExperimentalNot described
Receives: Drug: AZD9833 with palbociclib
AZD9833 with everolimus dose expansionExperimentalNot described
Receives: Drug: AZD9833 with everolimus
AZD9833 with everolimus dose escalationExperimentalNot described
Receives: Drug: AZD9833 with everolimus
AZD9833 with abemaciclib (± anastrozole) dose escalationExperimentalNot described
Receives: Drug: AZD9833 with abemaciclib
AZD9833 with abemaciclib (± anastrozole)dose expansionExperimentalNot described
Receives: Drug: AZD9833 with abemaciclib
AZD9833 with capivasertib dose escalationExperimentalNot described
Receives: Drug: AZD9833 with capivasertib
AZD9833 with capivasertib dose expansionExperimentalNot described
Receives: Drug: AZD9833 with capivasertib
AZD9833 with ribociclib (± anastrozole) dose escalationExperimentalNot described
Receives: Drug: AZD9833 with ribociclib
AZD9833 with ribociclib (± anastrozole) dose expansionExperimentalNot described
Receives: Drug: AZD9833 with ribociclib
AZD9833 with anastrozole dose escalationExperimentalNot described
Receives: Drug: AZD9833 with anastrozole
AZD9833 with anastrozole dose expansionExperimentalNot described
Receives: Drug: AZD9833 with anastrozole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The number of subjects with dose-limiting toxicity, as defined in the protocol.

    Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria.

    Measured: Minimum observation period 28 days on treatment.

  2. The number of subjects with treatment-related adverse events as assessed by CTCAE v4.03.

    Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of subjects with treatment-related adverse events assessed by CTCAE v4.03.

    Measured: Minimum observation period 28 days on treatment, and will continue until the subject is off the study (approximately 1 year).

Secondary outcomes (10)

  1. Objective Response Rate

    Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

    Measured: Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) until the end of the study (approximately 1 year).

  2. Duration of Response

    Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

    Measured: Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) until the end of the study (approximately 1 year).

  3. Clinical benefit rate at 24 weeks

    Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

    Measured: Up to 24 weeks

  4. Percentage Change in Tumour Size

    Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

    Measured: Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) until the end of the study (approximately 1 year).

  5. Progression Free Survival

    Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

    Measured: Weeks 8, 16 and 24 and then every 12 weeks (weeks 36, 48 and 60) until the end of the study (approximately 1 year).

  6. Maximum Observed Plasma Concentration (Cmax) of AZD9833 alone or in combination with Palbociclib, Everolimus, Abemaciclib, Capivasertib, Ribociclib or Anastrozole

    Blood samples will be collected to assess plasma concentrations of AZD9833 alone or in combination with Palbociclib, Everolimus, Abemaciclib, Capivasertib, Ribociclib or Anastrozole at a series of timepoints to derive Cmax

    Measured: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )

  7. Time to observed Cmax (Tmax) for AZD9833 alone or in combination with Palbociclib, Everolimus, Abemaciclib, Capivasertib, Ribociclib or Anastrozole

    Blood samples will be collected to assess plasma concentrations of AZD9833 alone or in combination with Palbociclib, Everolimus, Abemaciclib, Capivasertib, Ribociclib or Anastrozole at a series of timepoints to derive Tmax

    Measured: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )

  8. Area under the plasma concentration-time curve (AUC) for AZD9833 alone or in combination with Palbociclib, Everolimus, Abemaciclib, Capivasertib, Ribociclib or Anastrozole

    Blood samples will be collected to assess plasma concentrations of AZD9833 alone or in combination with Palbociclib, Everolimus, Abemaciclib, Capivasertib, Ribociclib or Anastrozole at a series of timepoints to derive AUC

    Measured: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )

  9. Renal clearance (CLR) for AZD9833

    Urine samples will be collected to assess urine concentrations of AZD9833 at a series of timepoints to derive renal clearance

    Measured: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )

  10. Assessment of biomarker changes

    Tumour samples will be collected to assess biomarker changes of estrogen receptor (ER), progesterone receptor (PgR) and Ki67 protein at a series of timepoints to derive AZD9833 activity in tumour cells.

    Measured: At pre-defined time intervals throughout the AZD9833 treatment period and at discontinuation. (approximately 1 year)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Aug 2018
  2. Study start11 Oct 2018
  3. Primary completion16 Sep 2024
  4. Study completion24 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Dose escalation and expansion, first-in-human study to evaluate safety and tolerability of AZD9833 alone (Parts A and B) or in combination with palbociclib (Parts C and D) or with everolimus (Parts E and F) or with abemaciclib (±anastrozole) (Parts G and H) or with capivasertib (Parts I and J) or with ribociclib (±anastrozole) (Parts K and L) or with anastrozole (Parts M and N) in women with endocrine-resistant ER+ HER2- breast cancer not amenable to curative treatment. Parts A, C, E, G, I, K, and M allow for dose escalation and/or de-escalation of AZD9833 alone or in combination with palbociclib, everolimus, abemaciclib (± anastrozole), capivasertib, ribociclib (± anastrozole) or anastrozole. Based on the findings in dose escalation, the expansions (Parts B, D, F, H, J, L, N) will further investigate selected doses of AZD9833, alone or in combination with palbociclib, everolimus ,abemaciclib (±anastrozole), capivasertib ,ribociclib(±anastrozole) and anastrozole.
Masking
None (open label)
Enrolment
396 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03616587
Sponsor's protocol ID
D8530C00001
Other IDs
138396, 2023-506890-37-00, 2018-000667-92, 2018, 2023
Acronym
SERENA-1
Status last verified
Aug 2026
First submitted
6 Jul 2018
Last updated
18 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD9833, AZD9833 with palbociclib and AZD9833 with everolimus in people with ER+ HER2- Advanced Breast Cancer, run by AstraZeneca at 17 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Spain, United Kingdom, United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The number of subjects with dose-limiting toxicity, as defined in the protocol. (time frame: Minimum observation period 28 days on treatment.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03616587.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.

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