A Phase 1 Study of AZD9833 in Japanese Women With ER Positive, HER2 Negative Advanced Breast Cancer

NCT04541433 | Completed Phase 1

• 1 other identifier: D8530C00006
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1, open-label study designed to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity of AZD9833 in Japanese women with endocrineresistant ER+ HER2- breast cancer that is not amenable to treatment with curative intent. This study consists of 2 cohorts, Cohort1 and Cohort2. In cohort 1 (for tolerability evaluation), a minimum of 3, or up to 6, evaluable Japanese patients with ER+ HER2- breast cancer will be enrolled. In cohort 2 (for exploratory research), at least 6 to maximum 12 evaluable Japanese patients with ER+ HER2- breast cancer will be enrolled.

Conditions

ER+ HER2- Advanced Breast Cancer

Keywords

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

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.

  From the first dose of study treatment up to and including Cycle1 Day28.

• The number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.

  Safety data will be assessed as the number of subjects with treatment-related adverse events.

  Minimum observation period 28 days on treatment or 28 days with at least 75% of the required dose and will continue until the subject is off the study (approximately 1 year).

Secondary Outcomes (7)

• Objective Response Rate

  At Cycle3 Day1, Cycle5 Day1, Cycle7 Day1 (each cycle is 28 days) and every 12 weeks until the end of the study (approximately 1 year).

• Duration of Response

  At Cycle3 Day1, Cycle5 Day1, Cycle7 Day1 (each cycle is 28 days) and every 12 weeks until the end of the study (approximately 1 year).

• Clinical benefit rate at 24 weeks

  Up to 24 weeks

• Percentage Change in Tumour Size

  At Cycle3 Day1, Cycle5 Day1, Cycle7 Day1 (each cycle is 28 days) and every 12 weeks until the end of the study (approximately 1 year).

• Progression Free Survival

  Up to objective disease progression or death (approximately 1 year).

Study Arms (1)

AZD9833 monotherapy

EXPERIMENTAL

Dose escalation of AZD9833 monotherapy for patients with ER+ HER2- advanced breast cancer

Drug: AZD9833

Interventions

AZD9833 DRUG

AZD9833 taken orally

AZD9833 monotherapy

Eligibility Criteria

• Age: 20 Years - 130 Years
• Gender Eligibility Details: Post-menopausal women In cohort 2, pre-menopausal women can also be enrolled.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent.
• \>= 20 years.
• Any menopausal status:
• Pre and Post menopausal defined according to standard criteria in the protocol.
• Histological or cytological confirmation of adenocarcinoma of the breast.
• Documented positive estrogen receptor status of primary or metastatic tumor tissue, according to the local laboratory parameters. HER-2 negative.
• 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 in the advanced setting is restricted 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.
• 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 computed tomography (CT), magnetic resonance imaging (MRI), or plain X-ray; or clinical examination.
• Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1

You may not qualify if:

• Intervention with any of the following:
• Any cytotoxic chemotherapy, investigational agents, or 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 study treatment.
• Medications or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 (CYP) 3A4/5 sensitive CYP2B6 substrates and drugs which are substrates of CYP2C9 and/or CYP2C19.
• Drugs that are known to prolong QT and have a known risk of Torsades de Pointes.
• Radiotherapy with a limited field of radiation for palliation within one week of the first dose of IMP, radiotherapy to more than 30% of the bone marrow or a wide field of radiation within 4 weeks of the first dose of IMP.
• Major surgical procedure or significant traumatic injury.
• Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting IMP.
• Presence of life-threatening metastatic visceral disease.
• Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses.
• Refractory nausea and vomiting, uncontrolled chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9833.
• History of another primary malignancy.
• Male subjects are excluded from this study.
• History of hypersensitivity to active or inactive excipients of AZD9833.
• The following cardiovascular criteria: QTcF \>470 ms, resting heart rate \<45 bpm, clinically significant abnormalities of resting electrocardiogram, uncontrolled hypertension, symptomatic hypotension, factors that increase the risk for QTc prolongation, left ventricular ejection fraction \<50%.
• Inadequate bone marrow reserve or organ function

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (3)

Research Site

Chūōku, 104-0045, Japan

Location

Research Site

Kashiwa, 277-8577, Japan

Location

Research Site

Kōtoku, 135-8550, Japan

Location

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms

Interventions

AZD9833

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: September 9, 2020
• Study Start: September 29, 2020
• Primary Completion: July 29, 2022
• Study Completion: June 23, 2025
• Last Updated: August 7, 2025

Record last verified: 2025-08

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 deidentified 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

JP (3)