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

NCT03616587 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: D8530C000011383962023-506890-37-002018-000667-92
• Study Type: interventional
• Target: 396
• Locations: 3 countries
• Sites: 17

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)

Conditions

ER+ HER2- Advanced Breast Cancer

Keywords

Breast Cancer; Phase 1; Safety; Tolerability; Pharmacokinetics; ER Positive; HER2 Negative; Advanced Breast Cancer; Camizestrant

Outcome Measures

Primary Outcomes (2)

• 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.

  Minimum observation period 28 days on treatment.

• 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.

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

Secondary Outcomes (10)

• Objective Response Rate

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

• Duration of Response

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

• Clinical benefit rate at 24 weeks

  Up to 24 weeks

• Percentage Change in Tumour Size

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

• Progression Free Survival

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

Study Arms (14)

AZD9833 monotherapy dose escalation

EXPERIMENTAL

Drug: AZD9833

AZD9833 monotherapy dose expansion

EXPERIMENTAL

Drug: AZD9833

AZD9833 with palbociclib dose escalation

EXPERIMENTAL

Drug: AZD9833 with palbociclib

AZD9833 with palbociclib dose expansion

EXPERIMENTAL

Drug: AZD9833 with palbociclib

AZD9833 with everolimus dose expansion

EXPERIMENTAL

Drug: AZD9833 with everolimus

AZD9833 with everolimus dose escalation

EXPERIMENTAL

Drug: AZD9833 with everolimus

AZD9833 with abemaciclib (± anastrozole) dose escalation

EXPERIMENTAL

Drug: AZD9833 with abemaciclib

AZD9833 with abemaciclib (± anastrozole)dose expansion

EXPERIMENTAL

Drug: AZD9833 with abemaciclib

AZD9833 with capivasertib dose escalation

EXPERIMENTAL

Drug: AZD9833 with capivasertib

AZD9833 with capivasertib dose expansion

EXPERIMENTAL

Drug: AZD9833 with capivasertib

AZD9833 with ribociclib (± anastrozole) dose escalation

EXPERIMENTAL

Drug: AZD9833 with ribociclib

AZD9833 with ribociclib (± anastrozole) dose expansion

EXPERIMENTAL

Drug: AZD9833 with ribociclib

AZD9833 with anastrozole dose escalation

EXPERIMENTAL

Drug: AZD9833 with anastrozole

AZD9833 with anastrozole dose expansion

EXPERIMENTAL

Drug: AZD9833 with anastrozole

Interventions

AZD9833 DRUG

Part A: AZD9833 monotherapy dose escalation.

AZD9833 monotherapy dose escalation

AZD9833 with palbociclib DRUG

Part C: AZD9833 in combination with palbociclib dose escalation

AZD9833 with palbociclib dose escalation

AZD9833 with everolimus DRUG

Part E: AZD9833 in combination with everolimus dose escalation

AZD9833 with everolimus dose escalation

AZD9833 with abemaciclib DRUG

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

AZD9833 with abemaciclib (± anastrozole) dose escalation

AZD9833 with capivasertib DRUG

Part I: AZD9833 in combination with capivasertib dose escalation

AZD9833 with capivasertib dose escalation

AZD9833 with ribociclib DRUG

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

AZD9833 with ribociclib (± anastrozole) dose escalation

AZD9833 with anastrozole DRUG

Part M: AZD9833 in combination with anastrozole dose escalation

AZD9833 with anastrozole dose escalation

Eligibility Criteria

• Age: 18 Years - 130 Years
• Gender Eligibility Details: Pre-menopausal or Post-menopausal women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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
• (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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (17)

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

Sarasota, Florida, 34232, United States

Location

Research Site

Philadelphia, Pennsylvania, 19111, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Salt Lake City, Utah, 84112, United States

Location

Research Site

Barcelona, 08035, Spain

Location

Research Site

Barcelona, 8036, Spain

Location

Research Site

Madrid, 28041, Spain

Location

Research Site

Madrid, 28050, Spain

Location

Research Site

Seville, 41013, Spain

Location

Research Site

Valencia, 46010, Spain

Location

Research Site

Cambridge, CB2 0QQ, United Kingdom

Location

Research Site

Leeds, LS9 7TF, United Kingdom

Location

Research Site

London, SW2 6JJ, United Kingdom

Location

Research Site

Manchester, M20 4GJ, United Kingdom

Location

Research Site

Sutton, SM1 2DL, United Kingdom

Location

Research Site

Sutton, SM2 5PT, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms

Interventions

AZD9833; palbociclib; Everolimus; abemaciclib; capivasertib; ribociclib; Anastrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Richard Baird, MD PhD FRCP

  Breast Cancer Research Unit, University of Cambridge

  PRINCIPAL INVESTIGATOR

• Justin Lindemann, MBChB MBA

  AstraZeneca

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 6, 2018
• First Posted: August 6, 2018
• Study Start: October 11, 2018
• Primary Completion: September 16, 2024
• Study Completion (Estimated): June 24, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

US (5); GB (6); ES (6)