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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- AstraZeneca
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- The number of subjects with dose-limiting toxicity, as defined in the protocol.
Study Overview
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.
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
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to 130 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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 CYP2C
- •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 AZD
- •History of another primary malignancy.
- •Male subjects are excluded from this study.
- •History of hypersensitivity to active or inactive excipients of AZD
- •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
- •Involvement in the planning and conduct of the study.
- •Judgment by the investigator that the patient should not participate in the study.
Arms & Interventions
AZD9833 monotherapy
Dose escalation of AZD9833 monotherapy for patients with ER+ HER2- advanced breast cancer
Intervention: AZD9833 (Drug)
Outcomes
Primary Outcomes
The number of subjects with dose-limiting toxicity, as defined in the protocol.
Time Frame: From the first dose of study treatment up to and including Cycle1 Day28.
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.
The number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.
Time Frame: 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).
Safety data will be assessed as the number of subjects with treatment-related adverse events.
Secondary Outcomes
- Clinical benefit rate at 24 weeks(Up to 24 weeks)
- Progression Free Survival(Up to objective disease progression or death (approximately 1 year).)
- Time to observed Cmax (Tmax) for AZD9833(At predefined intervals throughout the AZD9833 treatment period (approximately 12 weeks ))
- 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).)
- 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).)
- 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).)
- Maximum Observed Plasma Concentration (Cmax) of AZD9833(At predefined intervals throughout the AZD9833 treatment period (approximately 12 weeks ))