A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination in Chinese patients with ER Positive, HER2 Negative, Metastatic Breast Cancer
This study is designed to investigate and characterize the safety, tolerability and PK of AZD9833 monotherapy (Part A, Part B-cohort 1) or in combination with palbociclib (optional Part B cohort 2) or everolimus (optional Part B cohort 3) and to explore the preliminary anti-tumour activity in Chinese patients
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Research Site
Beijing, China
Research Site
Chengdu, China
Research Site
Shanghai, China
Research Site
Wuhan, China
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 of AZD9833 monotherapy. \[part A only\]
Time frame: Minimum observation period 28 days on treatment.
The number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.
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 v5.0 of AZD9833 monotherapy.
Time frame: 6 months after the last patient recruited starts study intervention or 28 days after the final patient discontinues study intervention
Plasma AZD9833 concentrations and derived PK parameters.
To characterise the single- and multiple-dose PK of AZD9833 monotherapy.
Time frame: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )
The number of subjects with treatment-related adverse events as assessed by CTCAE v5.0.
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 v5.0 of AZD9833 administered in combination with palbociclib or everolimus..
Time frame: 6 months after the last patient recruited starts study intervention or 28 days after the final patient discontinues study intervention
Plasma AZD9833 concentrations and derived PK parameters (for optional expansion cohorts Part B Cohorts 2 and 3 only). Everolimus (whole blood) concentrations and derived PK parameters (for optional expansion cohort Part B Cohort 3 only).
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Part B: AZD9833 with everolimus dose expansion
To characterise the single- and/or multiple-dose PK of AZD9833 administered in combination with palbociclib, and single- and/or multiple-dose PK of both AZD9833 and everolimus in combination.
Time frame: At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks )
Objective Response Rate
Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Time frame: Week 8 and week 16 and week 24 and then every 12 weeks (week 36, 48, 60) 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)
Time frame: Week 8 and week 16 and week 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
Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Time frame: Up to 24 weeks
Percentage Change in Tumour Size
Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Time frame: Week 8 and week 16 and week 24 and then every 12 weeks (weeks 36, 48 and 60) 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)
Time frame: From start of treatment to disease progression/latest date of evaluable RECIST assessment (approximate 1 year)