The Safety and Tolerability of GT0918 in Subjects With mHSPC and mCRPC
Condition: Metastatic Castrate Resistant Prostate Cancer (mCRPC); Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
MeSH terms: Prostatic Neoplasms
Intervention: GT0918
Intervention description: anti-tumor activity
Intervention MeSH terms: Androgens; Androgen Receptor Antagonists
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 61.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

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.
    

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 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.