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

ER+ HER2- Advanced Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04541433
• Other study ID #: D8530C00006
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 29, 2020
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: December 31, 2025
• Est. primary completion date: July 29, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 130 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• ER+ HER2- Advanced Breast Cancer

Intervention

Drug:
• AZD9833
AZD9833 taken orally

Locations

Country	Name	City	State
Japan	Research Site	Chuo-ku
Japan	Research Site	Kashiwa
Japan	Research Site	Koto-ku

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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).
Secondary	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).
Secondary	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
Secondary	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).
Secondary	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).
Secondary	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 )
Secondary	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 )

External Links

•   Redacted CSR synopsis
•   Related Info