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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Proxalutamide

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period is needed after 7-day single dose administration, until disease progression, intolerable toxicities (AEs), or withdrawn consent.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

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
  • Fujian
    • Guangzhou, Fujian, China
      • Sun-Yat-Sen University Cancer Center
  • Hebei
    • Shijiazhuang, Hebei, China
      • The Fourth Hospital of Hebei Medical University
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Ruijin Hospital, Shanghai Jiaotong University School Of Medicine
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Proxalutamide; 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; Stage1:Dose esclation. Stage2:the expansion cohort where one or no DLT takes place in planned study cohort.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Suzhou Kintor Pharmaceutical Inc,
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Sun Yat-sen University; Hunan Cancer Hospital; Peking University Cancer Hospital & Institute; Ruijin Hospital; Tianjin Medical University Cancer Institute and Hospital; Hebei Medical University Fourth Hospital
• Investigators: Study Director: Ke Chen, Suzhou Kintor Pharmaceuticals,inc

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2017
• Primary Completion (Actual): May 22, 2019
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: September 20, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): September 24, 2021
• Last Update Submitted That Met QC Criteria: September 22, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: metastatic breast cancer; Proxalutamide; AR-positive metastatic breast cancer; GT0918
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: GT0918-CN-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No