AZD9833 China PK Study

Study Overview
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Brief Summary
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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

Detailed Description
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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

Official Title
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A Phase 1 Dose Escalation and Expansion Study of AZD9833 Alone or in Combination With Palbociclib or Everolimus in Chinese Patients With Oestrogen Receptor Positive (ER+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (mBC)

Conditions
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ER+, HER2-, Metastatic Breast Cancer

Intervention / Treatment
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* Drug: AZD9833
* Drug: AZD9833
* Drug: AZD9833 with palbociclib
* Drug: AZD9833 with everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any menopausal status: Pre-menopausal women must have commenced treatment with an LHRH agonist at least 4 weeks prior to the start of study intervention and must be willing to continue to receive LHRH agonist therapy for the duration of the study. Post-menopausal defined according to standard criteria in the protocol. Histological or cytological confirmation of adenocarcinoma of the breast. Documented positive ER status and HER2 negative status of primary or metastatic tumour tissue. ECOG performance status 0 to 1. Metastatic disease and radiological or objective evidence of progression on or after the last systemic therapy prior to the start of study intervention. At least one lesion as per RECIST Version 1.1 that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI, or plain X-ray or clinical examination. Recurrence or progression on at least one line of endocrine therapy in the metastatic disease setting. For Part A and Part B cohort 1, patients should be eligible for SERD monotherapy treatment. For Part B Cohort 2, patients should be eligible for SERD treatment and CDK4/6 inhibitors, and prior treatment with CDK4/6 inhibitors is not permitted. For Part B Cohort 3, patients should be eligible for SERD treatment and mTOR inhibitors, and prior treatment with mTOR inhibitors is not permitted. Exclusion Criteria: Previous treatment with AZD9833. Presence of life-threatening metastatic visceral disease, uncontrolled CNS metastatic disease or life-threatening extensive hepatic involvement. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, or infection requiring intravenous antibiotic therapy, which makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol. Inadequate bone marrow reserve or organ function. Any clinically important and symptomatic heart disease. Any concurrent anti-cancer treatment. 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 (and palbociclib and everolimus). The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD9833 monotherapy dose escalation<br> | Drug: AZD9833<br>* Part A: AZD9833 monotherapy dose escalation.<br>|
| Experimental: AZD9833 monotherapy dose expansion<br> | Drug: AZD9833<br>* Part B: AZD9833 monotherapy dose expansion<br>|
| Experimental: AZD9833 with palbociclib dose expansion<br> | Drug: AZD9833 with palbociclib<br>* Part B: AZD9833 with palbociclib dose expansion<br>|
| Experimental: AZD9833 with everolimus dose expansion<br> | Drug: AZD9833 with everolimus<br>* Part B: AZD9833 with everolimus dose expansion<br>|

What is the study measuring?
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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 of AZD9833 monotherapy. [part A only] | 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. | 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. | At predefined intervals throughout the AZD9833 treatment period (approximately 16 weeks ) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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.. | 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). | 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. | 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) | 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) | 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) | 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) | 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) | From start of treatment to disease progression/latest date of evaluable RECIST assessment (approximate 1 year) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Open-label, Phase 1, Safety, Tolerability, Pharmacokinetics, ER Positive, HER2 Negative, Metastatic Breast Cancer