The Safety and Tolerability of GT0918 in Subjects With mHSPC and mCRPC

An Multi-Center, Randomized, Open-Label Study to Evaluate the Safety and Tolerability of GT0918 in Subjects With mHSPC and mCRPC Who Failed Either Abiraterone or Enzalutamide

This was a multiple-center, open-label, randomized, daily dose, two-sequence, expanded/phase II study in subjects with mHSPC or mCRPC who progressed after either abiraterone or enzalutamide treatment.

The objective of the study is to evaluate the safety and tolerability of proxalutamide and determine the RP2D for Ph III and/or other confirming studies.

Subjects will be randomized into the 2 treatment arms.

Study Overview

• Status: Completed
• Conditions: Metastatic Hormone-Sensitive Prostate Cancer (mHSPC); Metastatic Castrate Resistant Prostate Cancer (mCRPC)
• Intervention / Treatment: Drug: GT0918

Detailed Description

This study is an open-label, randomized, expanded/phase II study in subjects with mHSPC or mCRPC who progressed after either abiraterone or enzalutamide. All subjects will be randomized to take 400 mg or 500 mg of GT0918 by oral administration once daily on an empty stomach (2-3 hours after a meal) for initial treatment of 6 months. Randomization of subjects will be stratified by prior therapy (abiraterone or enzalutamide).

Subjects will continue treatment with GT0918 (proxalutamide) at their assigned dose on an empty stomach until disease progression, intolerable toxicities (AEs), or withdrawn consent. A post-treatment period of 4 weeks will commence that concludes with an end-of-study visit.

Disease progression will be assessed by three methods over the duration of the study. Subjects will be assessed for biochemical (PSA) progression measured monthly, as well as radiographic progression by CT scan or/and bone progression by radionuclide bone scan every 12-weeks. Progressive disease will be considered on the occurrence of the first assessed progression event. Subjects with PSA progression only may continue the study until radiographic or bone progression at the discretion of the Investigator and with agreement by the sponsor or their authorized medical monitor.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Phoebe Zhang, PhD; Phone Number: +1-984-208-1255; Email: pzhang@kintor.com.cn

Study Locations

• United States
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Maryland
    • Towson, Maryland, United States, 21204
      • Chesapeake Urology Research Associates
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • G U Research Network
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New York
    • Bronx, New York, United States, 10469
      • New York Cancer & Blood Specialists
    • East Setauket, New York, United States, 11733
      • New York Cancer & Blood Specialists
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Signed informed consent obtained prior to any study-related procedure being performed.
2. Subjects at least 18 years of age or older at the time of consent.
3. Subjects with histologically confirmed mHSPC or mCRPC who received abiraterone or enzalutamide for the hormonal treatment of 6 months or longer.
4. Subjects with mHSPC are required to have no prior ADT (androgen deprivation therapy) or orchiectomy. For mCRPC, ongoing androgen deprivation therapy with a luteinizing hormonereleasing hormone (LHRH) "super-agonist" or antagonist, or bilateral orchiectomy. Serum testosterone level is < 50 ng/dL (< 0.5 ng/mL, < 1.7 nmol/L) at screening.
5. Metastatic disease documented by computed tomography (CT)/magnetic resonance imaging (MRI) or bone scan.

6. Progressive disease despite hormonal treatment with abiraterone or enzalutamide, but not both. However, if either of these 2 drugs was used less than 3 months due to toxicity, the patient is eligible. One line of chemotherapy is eligible. Progressive disease is defined by 1 or more of the following criteria:

   1. Subjects with a rising prostate specific antigen (PSA) value > 2 ng/mL in at least 2 measurements, at least 1 week apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for the rising PSA is required to document progression.
   2. Subjects with measurable disease, progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
   3. Subjects with metastatic bone disease, progression defined by 2 or more new lesions in a radionuclide bone scan.
7. ECOG performance status of 0-1

8. Screening blood counts of the following:

   1. Absolute neutrophil count ≥ 1500/μL
   2. Platelets ≥ 100,000/μL
   3. Hemoglobin > 9 g/dL (if asymptomatic).

9. Screening chemistry values of the following:

   1. Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 × upper limit of the normal reference range (ULN)
   2. Total bilirubin ≤ 2 × ULN
   3. Creatinine ≤ 1.5 × ULN
   4. Albumin > 2.8 g/dL.
10. At screening, life expectancy of at least 6 months.
11. Subjects whose partners are women of childbearing potential (WOCBP) must use an adequate method of birth control while on study drug and for at least 3 months after discontinuation of study drug.
12. Subject is willing and able to comply with all protocol required visits and assessments.

Exclusion criteria:

1. Discontinuation of enzalutamide or abiraterone less than 3 weeks prior to the start of study medication.
2. Prior chemotherapy and experimental therapy (Poly (ADP-ribose) polymerase (PARP) or checkpoint inhibitor)
3. Ongoing acute treatment-related toxicity associated with a previous therapy greater than grade 1 except for grade 2 alopecia or neuropathy.
4. History of impaired adrenal gland function (e.g., Addison's disease, Cushing's syndrome).
5. Known gastrointestinal disease or condition that affects the absorption of proxalutamide.
6. History of congestive heart failure New York Heart Association (NYHA) class III or IV or uncontrolled hypertension at screening.
7. History or family history of long QT syndrome, or ECG corrected QT interval equal to and over 500 ms (CTCAE grade 2) at baseline.
8. History of other malignancy within the previous 3 years, except basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer.
9. Use of systemic glucocorticoid (e.g., prednisone, dexamethasone) within 14 days prior to the start of study medication. Inhaled or topical steroids are allowed.
10. Co-administration of CYP3A4 ligands that serve as substrates or induce or inhibit the enzyme.
11. Prior use of any herbal products known to decrease PSA levels (e.g., PC-SPES or saw palmetto) within 30 days prior to the start of study medication.
12. Major surgery within 30 days prior to the start of study medication.
13. Blood transfusion (including blood products) within 1 week of screening.
14. Serious persistent infection within 14 days prior to the start of study medication.
15. Serious concurrent medical condition including CNS disorders.
16. Previous history of difficulty swallowing capsules.
17. Known hypersensitivity to GT0918 or its excipients.
18. Any condition that, in the opinion of the investigator, would impair the subject's ability to comply with study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: 400 mg /day of GT0918; Group 1: Post enzalutamide failure Group 2: Post abiraterone failure	Drug: GT0918; anti-tumor activity; Other Names: proxalutamide; androgen receptor antagonist
Experimental: Arm 2: 500 mg/day of GT0918; Group 1: Post enzalutamide failure Group 2: Post abiraterone failure	Drug: GT0918; anti-tumor activity; Other Names: proxalutamide; androgen receptor antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Safety and Tolerability of GT0918 and Select the RP2D for Future Clinical Trial Study.	To evaluate the safety and tolerability of GT0918 assessed by AEs, SAEs between 400 mg arm vs. 500 mg arm with mHSPC or mCRPC who failed either abiraterone or enzalutamide treatment The percetage of AE and SAE would be evaluated in subjects with mHSPC and to determine the recommended Phase II dose (RP2D) over 6 months or longer treatment	Average of 24 weeks, up to a maximum of 30 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Subjects Achieving a ≥50% Reduction in PSA at 12 Weeks and 24 Weeks	The percentage of subjects achieving a ≥50% reduction in PSA at 3 months (12 weeks) as compared to baseline (study entry) was determined.	24 weeks
Time to PSA Progression	Time to PSA Progression in 400mg group and 500mg group	24 weeks
PSA Maximum Change at 12 Weeks	The percentage of change of PSA from baseline at Week 12 was calculated. Maximum percentage change of PSA from baseline at any time was calculated.	24 weeks

Collaborators and Investigators

• Sponsor: Suzhou Kintor Pharmaceutical Inc,
• Investigators: Study Director: Phoebe Zhang, PhD, Suzhou Kintor Pharmaceuticals Inc

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2019
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): September 19, 2022

Study Registration Dates

• First Submitted: March 27, 2019
• First Submitted That Met QC Criteria: April 1, 2019
• First Posted (Actual): April 2, 2019

Study Record Updates

• Last Update Posted (Actual): February 12, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Androgen Antagonists; Androgens; Androgen Receptor Antagonists
• Other Study ID Numbers: GT0918-US-1002

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