Description:
This study is an open-label, randomized, expanded/phase II study in subjects with metastatic
castrate resistant prostate cancer (mCRPC) who progressed after either abiraterone or
enzalutamide.
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.
Title
- Brief Title: the Safety and Tolerability of Proxalutamide (GT0918) in Subjects With Metastatic Castrate Resistant Prostate Cancer
- Official Title: An Extended/Phase 2, Multi-Center, Randomized, Open-Label Study to Evaluate the Safety and Tolerability of GT0918 in Subjects With Metastatic Castrate Resistant Prostate Cancer (mCRPC) Who Failed Either Abiraterone or Enzalutamide
Clinical Trial IDs
- ORG STUDY ID:
GT0918-US-1002
- NCT ID:
NCT03899467
Conditions
- Metastatic Castrate Resistant Prostate Cancer (mCRPC)
Interventions
Drug | Synonyms | Arms |
---|
GT0918 | proxalutamide, androgen receptor antagonist | Arm 1: biological dose group |
Purpose
This study is an open-label, randomized, expanded/phase II study in subjects with metastatic
castrate resistant prostate cancer (mCRPC) who progressed after either abiraterone or
enzalutamide.
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.
Detailed Description
This study is an open-label, randomized, expanded/phase II study in subjects with metastatic
castrate resistant prostate cancer (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empty stomach until disease progression, intolerable toxicities (AEs), or withdrawn consent.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.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm 1: biological dose group | Experimental | 400mg/day of proxalutamide
Group 1: Post enzalutamide failure
Group 2: Post abiraterone failure | |
Arm 2: MTD dose group | Experimental | 500mg/day of proxalutamide
Group 1: Post enzalutamide failure
Group 2: Post abiraterone failure | |
Eligibility Criteria
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 metastatic castrate resistant prostate cancer
(mCRPC) who progressed after abiraterone or enzalutamide.
4. Ongoing androgen deprivation therapy with a luteinizing hormone-releasing hormone
(LHRH) "super-agonist" or antagonist, or bilateral orchiectomy and serum testosterone
level < 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, radiation, sipuleucel-T or other experimental immunotherapy less
than 3 weeks prior to the start of study medication
3. Prior chemotherapies more than 1 line.
4. Ongoing acute treatment-related toxicity associated with a previous therapy greater
than grade 1 except for grade 2 alopecia or neuropathy.
5. History of impaired adrenal gland function (e.g., Addison's disease, Cushing's
syndrome).
6. Known gastrointestinal disease or condition that affects the absorption of
proxalutamide.
7. History of congestive heart failure New York Heart Association (NYHA) class III or IV
or uncontrolled hypertension at screening.
8. History or family history of long QT syndrome, or ECG corrected QT interval equal to
and over 500 ms (CTCAE grade 2) at baseline.
9. History of other malignancy within the previous 3 years, except basal cell or squamous
cell carcinoma, or non-muscle invasive bladder cancer.
10. Use of systemic glucocorticoid (e.g., prednisone, dexamethasone) within 14 days prior
to the start of study medication. Inhaled or topical steroids are allowed.
11. Co-administration of CYP3A4 ligands that serve as substrates or induce or inhibit the
enzyme (See Appendix 4 for the list of medications).
12. 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.
13. Major surgery within 30 days prior to the start of study medication.
14. Blood transfusion (including blood products) within 1 week of screening.
15. Serious persistent infection within 14 days prior to the start of study medication.
16. Serious concurrent medical condition including CNS disorders.
17. Previous history of difficulty swallowing capsules.
18. Known hypersensitivity to GT0918 or its excipients (See Appendix 5 for drug details).
19. Any condition that, in the opinion of the investigator, would impair the subject's
ability to comply with study procedures.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Male |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | recommended Phase 2 dose (RP2D) |
Time Frame: | 6 month |
Safety Issue: | |
Description: | determine the RP2D for Ph III and/or other confirming studies |
Secondary Outcome Measures
Measure: | >50% PSA suppression |
Time Frame: | 12 weeks |
Safety Issue: | |
Description: | To evaluate proportion of subjects with a > 50% PSA suppression at 12 weeks |
Measure: | percentage of radiographic disease progression |
Time Frame: | 6 and 12 months |
Safety Issue: | |
Description: | To evaluate percentage of radiographic disease progression at 6 and 12 months |
Measure: | radiographic and bone progression time |
Time Frame: | 6 month |
Safety Issue: | |
Description: | To evaluate time to radiographic and bone progression |
Measure: | the time to PSA progression |
Time Frame: | 6 month |
Safety Issue: | |
Description: | To evaluate the time to PSA progression |
Measure: | exploratory biomarkers: cell free circulating tumor DNA (ct-DNA)/RNA (ct-RNA) |
Time Frame: | 6 month |
Safety Issue: | |
Description: | To identify exploratory biomarkers to characterize androgen receptor (AR) inhibition and/or down-regulation by proxalutamide |
Measure: | exploratory biomarkers: Circulating tumor cells (CTC) |
Time Frame: | 6 months |
Safety Issue: | |
Description: | anti-tumor activities |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Suzhou Kintor Pharmaceutical Inc, |
Last Updated
July 23, 2021