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

A Phase 1, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti- Tumor Activity of AZD9833 in Japanese Women With ER Positive, HER2 Negative Advanced Breast Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: ER+ HER2- Advanced Breast Cancer
• Intervention / Treatment: Drug: AZD9833

Detailed Description

Objectives:

Primary objective:

To investigate the safety and tolerability of AZD9833 in Japanese women with ER+ HER2- advanced breast cancer

Secondary objective:

To assess the anti-tumor activity and efficacy of AZD9833

Exploratory objectives:

To investigate AZD9833 activity in tumor cells

Overall design:

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. Eligible patients will receive AZD9833. In cohort 1 (for tolerability evaluation), a minimum of 3 to maximum 6 evaluable patients will be enrolled.

For cohort 2, if paired biopsy after administration of the study drug becomes inoperable during administration of the study drug, additional subjects can be added to obtain an evaluable biopsy sample.

In cohort 2 (for exploratory research), eligible patients will receive AZD9833 once daily and at least 6 to maximum 12 patients will be enrolled. In cohort 2, paired biopsy sample will be collected from at least 6 and maximum 12 patients. If paired biopsy after administration of the study drug becomes inoperable during administration of the study drug, additional subjects can be added to obtain an evaluable biopsy sample.

Number of Subjects:

Maximum 18 evaluable subjects will be enrolled in this study.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chuo-ku, Japan, 104-0045
    • Research Site
  • Kashiwa, Japan, 277-8577
    • Research Site
  • Koto-ku, Japan, 135-8550
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Major Inclusion Criteria:

1. Signed written informed consent.
2. >= 20 years.

3. Any menopausal status:

   Pre and Post menopausal defined according to standard criteria in the protocol.

4. Histological or cytological confirmation of adenocarcinoma of the breast.
5. Documented positive estrogen receptor status of primary or metastatic tumor tissue, according to the local laboratory parameters. HER-2 negative.
6. Metastatic or locoregionally recurrent disease and radiological or objective evidence of progression on or after the last systemic therapy prior to starting IMP.

7. Prior chemotherapy, endocrine therapy and other therapy in the advanced setting is restricted 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.
8. 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.
9. Eastern Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status 0 to 1

Major Exclusion Criteria:

1. Intervention with any of the following:

   1. 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.
   2. 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.
   3. Drugs that are known to prolong QT and have a known risk of Torsades de Pointes.
   4. 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.
   5. Major surgical procedure or significant traumatic injury.
2. Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting IMP.
3. Presence of life-threatening metastatic visceral disease.
4. Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses.
5. 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.
6. History of another primary malignancy.
7. Male subjects are excluded from this study.
8. History of hypersensitivity to active or inactive excipients of AZD9833.
9. 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%.
10. Inadequate bone marrow reserve or organ function
11. Involvement in the planning and conduct of the study.
12. Judgment by the investigator that the patient should not participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD9833 monotherapy; Dose escalation of AZD9833 monotherapy for patients with ER+ HER2- advanced breast cancer	Drug: AZD9833; AZD9833 taken orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical benefit rate at 24 weeks	Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)	Up to 24 weeks
Objective Response Rate	Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)	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	Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)	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).
Percentage Change in Tumour Size	Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)	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	Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)	Up to objective disease progression or death (approximately 1 year).
Maximum Observed Plasma Concentration (Cmax) of AZD9833	Blood samples will be collected to assess plasma concentrations of AZD9833 at a series of timepoints to derive Cmax	At predefined intervals throughout the AZD9833 treatment period (approximately 12 weeks )
Time to observed Cmax (Tmax) for AZD9833	Blood samples will be collected to assess plasma concentrations of AZD9833 at a series of timepoints to derive Tmax	At predefined intervals throughout the AZD9833 treatment period (approximately 12 weeks )

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Related Info
• Redacted CSR synopsis

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2020
• Primary Completion (Actual): July 29, 2022
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 20, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Breast Cancer; Advanced Breast Cancer; Pharmacokinetics; Phase 1; Tolerability; HER2 Negative; ER Positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: D8530C00006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing 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.
• IPD Sharing 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No