Metastatic Castrate Resistant Prostate Cancer (mCRPC), Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Conditions
Brief summary
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.
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(proxalutamide) at their assigned dose on an empty stomach until disease progression, intolerable toxicities (AEs), or withdrawn consent.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.
Interventions
DRUGGT0918
anti-tumor activity
Sponsors
Suzhou Kintor Pharmaceutical Inc,
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Safety and Tolerability of GT0918 and Select the RP2D for Future Clinical Trial Study. | Average of 24 weeks, up to a maximum of 30 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Subjects Achieving a ≥50% Reduction in PSA at 12 Weeks and 24 Weeks | 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. |
| Time to PSA Progression | 24 weeks | Time to PSA Progression in 400mg group and 500mg group |
| PSA Maximum Change at 12 Weeks | 24 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. |
Countries
United States
Participant flow
Recruitment details
The anticipated 60 subjects would be enrolled per protocol; Actually, total 61 subjects were randomized to take 400 mg or 500 mg of GT0918.
Pre-assignment details
The anticipated 60 subjects would be enrolled per protocol; Actually, total 61 subjects were randomized to take 400 mg or 500 mg of GT0918; 31patients were enrolled in 400mg arm and 30 patiens were enrolled in 500mg arm respectively. Randomization of subjects were stratified by prior therapy (abiraterone or enzalutamide).The post enzalutamide and post abiraterone groups were not pre-specified to be analyzed and as separate Arms/Groups.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: 400 mg /Day of GT0918 Group 1: Post enzalutamide failure
Group 2: Post abiraterone failure
GT0918: anti-tumor activity | 31 |
| Arm 2: 500 mg/Day of GT0918 Group 1: Post enzalutamide failure
Group 2: Post abiraterone failure
GT0918: anti-tumor activity | 30 |
| Total | 61 |
Baseline characteristics
| Characteristic | Arm 1: 400 mg /Day of GT0918 | Arm 2: 500 mg/Day of GT0918 | Total |
|---|---|---|---|
| Age, Continuous | 72.8 years STANDARD_DEVIATION 8.71 | 74.3 years STANDARD_DEVIATION 7.39 | 73.5 years STANDARD_DEVIATION 8.06 |
| BMI | 29.4 Kg/mg^2 | 29.1 Kg/mg^2 | 29.3 Kg/mg^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 29 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 27 Participants | 22 Participants | 49 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 31 Participants | 30 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 30 |
| other Total, other adverse events | 28 / 31 | 26 / 30 |
| serious Total, serious adverse events | 6 / 31 | 12 / 30 |
Outcome results
Primary
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
Time frame: Average of 24 weeks, up to a maximum of 30 weeks
Population: The Safety Analysis Set (SS) included all 61 subjects who have taken at least one dose of study medication;31 subjects and 30 subjects were incuded in 400mg daily arm and 500mg daily arm,respevtively
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: 400 mg /Day of GT0918 | Evaluate the Safety and Tolerability of GT0918 and Select the RP2D for Future Clinical Trial Study. | TEAE | 28 Participants |
| Arm 1: 400 mg /Day of GT0918 | Evaluate the Safety and Tolerability of GT0918 and Select the RP2D for Future Clinical Trial Study. | SAE | 6 Participants |
| Arm 2: 500 mg/Day of GT0918 | Evaluate the Safety and Tolerability of GT0918 and Select the RP2D for Future Clinical Trial Study. | TEAE | 29 Participants |
| Arm 2: 500 mg/Day of GT0918 | Evaluate the Safety and Tolerability of GT0918 and Select the RP2D for Future Clinical Trial Study. | SAE | 12 Participants |
Secondary
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.
Time frame: 24 weeks
Population: The percentage change of PSA from baseline at any visit was calculated for the FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: 400 mg /Day of GT0918 | PSA Maximum Change at 12 Weeks | -5.58 percent change |
| Arm 2: 500 mg/Day of GT0918 | PSA Maximum Change at 12 Weeks | 45.61 percent change |
Secondary
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.
Time frame: 24 weeks
Population: The Full Analysis Set (FAS) will include subjects who have post-baseline PSA assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1: 400 mg /Day of GT0918 | The Percentage of Subjects Achieving a ≥50% Reduction in PSA at 12 Weeks and 24 Weeks | PSA ≥50% reduction at Week 12 | 2 Participants |
| Arm 1: 400 mg /Day of GT0918 | The Percentage of Subjects Achieving a ≥50% Reduction in PSA at 12 Weeks and 24 Weeks | PSA ≥50% reduction at Week 24 | 1 Participants |
| Arm 2: 500 mg/Day of GT0918 | The Percentage of Subjects Achieving a ≥50% Reduction in PSA at 12 Weeks and 24 Weeks | PSA ≥50% reduction at Week 24 | 1 Participants |
| Arm 2: 500 mg/Day of GT0918 | The Percentage of Subjects Achieving a ≥50% Reduction in PSA at 12 Weeks and 24 Weeks | PSA ≥50% reduction at Week 12 | 1 Participants |
Secondary
Time to PSA Progression
Time to PSA Progression in 400mg group and 500mg group
Time frame: 24 weeks
Population: The Full Analysis Set (FAS) will include subjects who have at least one post-treatment tumor assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1: 400 mg /Day of GT0918 | Time to PSA Progression | 85 day |
| Arm 2: 500 mg/Day of GT0918 | Time to PSA Progression | 83.5 day |