Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer

Study Overview
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Brief Summary
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This study is a multi-center, open-label, dose-esclation I/Ib clinical study to explore safety, efficacy an pharmacokinetics of proxalutamide in patients with metastatic breast cancer. This study includes two stages, stage I: single- and multiple-dose tolerance and pharmacokinetic study; stage 2: preliminary efficacy and safety study.

Detailed Description
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This study is a multi-center, open-label, dose-esclation study. Subjects will be enrolled to the 100mg, 200mg, 300mg, 400mg and 500mg group in turn. Unless DLT was found, the dose esclation will continue. 28 days of DLT observation period is needed after 7-day single dose administration, until disease progression, intolerable toxicities (AEs), or withdrawn consent. After the completion of stage 1, 2 doses for the stage 2 will be determined. In stage 2, patients with AR-positive metastatic breast cancer will be selected to explore the efficacy and safety of proxalutamide, and biomarkers will be explored.

Official Title
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Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer: an Open-label, Multi-center, Dose-escalating，Phase I/Ib Study.

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Proxalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years female; Stage 1:Histology or cytology confirmed metastatic breast cancer, first-line chemotherapy or targeted therapy failure or intolerance Stage 2: Histological or cytological confirmed metastatic breast cancer patients who failed or intolerant to anti-tumor therapy; have a positive AR test result; At least one measurable lesion based on RECIST version 1.1 ; ECOG performance status: 0-1; Have a predicted life expectancy of greater than 3 months; The functions of the important organs are confirmed with the following requirement: Hemoglobin (HGB) ≥ 90 g/L(no blood transfusion within 14 days ); Absolute neutrophil count (ANC) ≥ 1.5×10^9/L； Platelets (PLT) ≥ 100×10^9/L(If the coagulation function is normal,Platelets (PLT) ≥ 75×10^9/L )； Total bilirubin (TBIL) ≤ 1.5× Upper limit of normal value (ULN) -Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine - Aminotransferase (ALT) ≤2.5× ULN Understand and voluntarily sign the informed consent form； Subject is willing and able to comply with all protocol required visits and assessments； Exclusion Criteria: Pregnant, lactating women, or those who have fertility and are reluctant to take effective contraceptive measures; Prior chemotherapy, radiation, targeted therapy ,androgen receptor inhibitors therapy (abiraterone,enzalutamide,etc )，other endocrine therapy ，and has acceptted traditional chinese herbal medicine treatment less than 4 weeks prior to the start of study medication. Has severe cardiovascular disease The toxicity of the previous treatment plan has not been restored before enrollment, and there is still non-hematologic toxicity of grade 1 or above (except for hair loss) Known gastrointestinal disease or condition that affects the absorption of GT0918; Known or suspected brain metastases, including the central nervous system and spinal cord compression or meningeal metastasis; History of severe central nervous system diseases (including patients with epilepsy); Known hypersensitivity to proxalutmide or its excipients. Participated in clinical trials of other drugs or medical devices within one month prior to screening, or plan to participate in any other clinical trials during the study period; Subjects with any other serious disease considered by the investigator not in the condition to enter into the trial;

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proxalutamide<br>Stage one - Dose climbing: Each dose cohort will assess toxicity within the 35 days following the first dose of GT0918. Stage two- the expansion cohort : 30 patients will be enrolled to the 200mg cohort . 15 patients will be enrolled to the 300mg cohort. | Drug: Proxalutamide<br>* Stage1:Dose esclation. Stage2:the expansion cohort where one or no DLT takes place in planned study cohort.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting Toxicity(DLT) | Each dose cohort will initially include 3 evaluable patients for assessment of toxicity within the 35 days following the first dose of GT0918. | 35 days | 
| maximum tolerated dose (MTD) | 100 mg, 200 mg, 300 mg, 400 mg or 500 mg of GT0918 | 35 days | 
| Disease Control Rate(DCR) | Preliminary evaluation of the DCR of GT0918 tablets in AR positive metastatic breast cancer patients, and determination of the recommended dose of proclamine in clinical trials. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum concentration (Cmax) | Pharmacokinetics | 35 days | 
| time that maximum concentration is observed (tmax) | Pharmacokinetics | 35 days | 
| area under the concentration time-curve from time zero to infinity (AUC0∞) | Pharmacokinetics | 35 days | 
| terminal elimination half life (t½) | Pharmacokinetics | 35 days | 
| drug clearance (CL) | Pharmacokinetics | 35 days | 
| apparent volume of distribution (Vd) | Pharmacokinetics | 35 days | 
| Number of participants with treatment-related adverse events as assessed by CTCAE V4.03 | 200 mg, 300 mg of GT0918 | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AR-positive metastatic breast cancer, Proxalutamide, metastatic breast cancer, GT0918