Clinical trial NCT04103853: Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer
Official title: Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer: an Open-label, Multi-center, Dose-escalating，Phase I/Ib Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Breast Cancer
Keywords: AR-positive metastatic breast cancer
Proxalutamide
metastatic breast cancer
GT0918
Lead sponsor: Suzhou Kintor Pharmaceutical Inc,
Sponsor class: INDUSTRY
Collaborators: name: Peking University Cancer Hospital & Institute
name: Tianjin Medical University Cancer Institute and Hospital
name: Sun Yat-sen University
name: Ruijin Hospital
name: The First Affiliated Hospital with Nanjing Medical University
name: Hebei Medical University Fourth Hospital
name: Hunan Cancer Hospital
First posted: 2019-09-26
Enrollment: 63
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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period is needed after 7-day single dose administration, until disease progression, intolerable toxicities (AEs), or withdrawn consent.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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years female;
2. 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;
3. At least one measurable lesion based on RECIST version 1.1 ;
4. ECOG performance status: 0-1;
5. Have a predicted life expectancy of greater than 3 months;
6. 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
7. Understand and voluntarily sign the informed consent form；
8. Subject is willing and able to comply with all protocol required visits and assessments；

Exclusion Criteria:

1. Pregnant, lactating women, or those who have fertility and are reluctant to take effective contraceptive measures;
2. 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.
3. Has severe cardiovascular disease
4. 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)
5. Known gastrointestinal disease or condition that affects the absorption of GT0918;
6. Known or suspected brain metastases, including the central nervous system and spinal cord compression or meningeal metastasis;
7. History of severe central nervous system diseases (including patients with epilepsy);
8. Known hypersensitivity to proxalutmide or its excipients.
9. 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;
10. Subjects with any other serious disease considered by the investigator not in the condition to enter into the trial;

Primary outcomes:
measure: Dose-limiting Toxicity(DLT)
timeFrame: 35 days
measure: maximum tolerated dose (MTD)
timeFrame: 35 days
measure: Disease Control Rate(DCR)
timeFrame: 16 weeks
Secondary outcomes:
measure: maximum concentration (Cmax)
timeFrame: 35 days
measure: time that maximum concentration is observed (tmax)
timeFrame: 35 days
measure: area under the concentration time-curve from time zero to infinity (AUC0∞)
timeFrame: 35 days
measure: terminal elimination half life (t½)
timeFrame: 35 days
measure: drug clearance (CL)
timeFrame: 35 days
measure: apparent volume of distribution (Vd)
timeFrame: 35 days
measure: Number of participants with treatment-related adverse events as assessed by CTCAE V4.03
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun-Yat-sen University Cancer center
state: Fujian
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
Study officials:
affiliation: Suzhou Kintor Pharmaceuticals,inc
name: Ke Chen
role: STUDY_DIRECTOR
References:
citation: Jiang H, Ouyang Q, Yin Y, Tong Z, Shen K, Yuan Z, Geng C, Liu Y, Song G, Ran R, Li W, Qu Q, Wang M, Meng L, Tong Y, Li H. Proxalutamide in patients with AR-positive metastatic breast cancer: Results from an open-label multicentre phase Ib study and biomarker analysis. Eur J Cancer. 2022 Nov;176:1-12. doi: 10.1016/j.ejca.2022.08.025. Epub 2022 Sep 28.
citation: Li H, Song G, Zhou Q, Ran R, Jiang H, Zhang R, Liu Y, Zhang J, Meng L, Ma L, Sun Y, Wang M, Zhou Q, Yan H, Zhou Q, Dong X, Tong Y. Activity of preclinical and phase I clinical trial of a novel androgen receptor antagonist GT0918 in metastatic breast cancer. Breast Cancer Res Treat. 2021 Oct;189(3):725-736. doi: 10.1007/s10549-021-06345-x. Epub 2021 Aug 14.