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

Metastatic Breast Cancer Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04103853
• Other study ID #: GT0918-CN-2001
• Status: Completed
• Phase: Phase 1
• Start date: September 6, 2017
• Est. completion date: June 30, 2020

Study information

• Verified date: September 2021
• Source: Suzhou Kintor Pharmaceutical Inc,
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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period is needed after 7-day single dose administration, until disease progression, intolerable toxicities (AEs), or withdrawn consent.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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: June 30, 2020
• Est. primary completion date: May 22, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Proxalutamide
Stage1:Dose esclation. Stage2:the expansion cohort where one or no DLT takes place in planned study cohort.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	Sun-Yat-sen University Cancer center	Guangzhou	Fujian
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin

Sponsors (8)

Lead Sponsor	Collaborator
Suzhou Kintor Pharmaceutical Inc,	Beijing Cancer Hospital, Hebei Medical University Fourth Hospital, Hunan Cancer Hospital, Ruijin Hospital, Sun Yat-sen University, The First Affiliated Hospital with Nanjing Medical University, Tianjin Medical University Cancer Institute and Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	maximum tolerated dose (MTD)	100 mg, 200 mg, 300 mg, 400 mg or 500 mg of GT0918	35 days
Primary	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	maximum concentration (Cmax)	Pharmacokinetics	35 days
Secondary	time that maximum concentration is observed (tmax)	Pharmacokinetics	35 days
Secondary	area under the concentration time-curve from time zero to infinity (AUC08)	Pharmacokinetics	35 days
Secondary	terminal elimination half life (t½)	Pharmacokinetics	35 days
Secondary	drug clearance (CL)	Pharmacokinetics	35 days
Secondary	apparent volume of distribution (Vd)	Pharmacokinetics	35 days
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE V4.03	200 mg, 300 mg of GT0918	16 weeks