Clinical Trials /

the Safety and Tolerability of Proxalutamide (GT0918) in Subjects With Metastatic Castrate Resistant Prostate Cancer

NCT03899467

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
GT0918proxalutamide, androgen receptor antagonistArm 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      empty stomach until disease progression, intolerable toxicities (AEs), or withdrawn consent.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

NameTypeDescriptionInterventions
Arm 1: biological dose groupExperimental400mg/day of proxalutamide Group 1: Post enzalutamide failure Group 2: Post abiraterone failure
  • GT0918
Arm 2: MTD dose groupExperimental500mg/day of proxalutamide Group 1: Post enzalutamide failure Group 2: Post abiraterone failure
  • GT0918

Eligibility Criteria

        Inclusion Criteria:

          1. Written 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. 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 > 5 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.

          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.

         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.

         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

September 12, 2019