Help guide our efforts to modernize
Send us your comments by March 14, 2020. Menu

Safety, Tolerability, and PK of GT0918 (Proxalutamide) in Subjects With Metastatic Castrate Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02826772
Recruitment Status : Active, not recruiting
First Posted : July 11, 2016
Last Update Posted : July 29, 2019
Information provided by (Responsible Party):
Suzhou Kintor Pharmaceutical Inc,

Brief Summary:

This study is an open-label, non-randomized, dose escalation study in subjects with metastatic castrate resistant prostate cancer (mCRPC) who progressed after both hormonal therapy (abiraterone or enzalutamide) and chemotherapy (docetaxel), or cannot tolerate either or both therapies.

Phase 1 (dose escalation stage): Multiple dose escalations of GT0918 (proxalutamide) to establish safety and tolerability.

Condition or disease Intervention/treatment Phase
Metastatic Castrate Resistant Prostate Cancer (mCRPC) Drug: GT0918 Phase 1

Detailed Description:

The starting dose cohort in the dose escalation stage will be 50 mg GT0918 (proxalutamide) PO once daily administered to 3 subjects in a fasted state. The next dose cohort in the dose escalation stage will be 100 mg PO once daily administered to 6 subjects in a fasted state with escalation to the following dose levels, each having a total of at least 6 subjects per cohort: 200 mg, 300 mg, 400 mg, 500 mg and 600 mg. Dose escalation can occur after a minimum of 3 subjects in the 50 mg dose level have completed 28 days of treatment, no DLTs have occurred and the safety review of the cohort has been performed. Dose escalation in the remaining cohorts can occur after a minimum of 6 subjects have completed 28 days of treatment, either no DLTs or ≤1 subject has a DLT, and the safety review of the cohort has been performed.

During the dose escalation stage, all subjects will take GT0918 oral administration once daily on an empty stomach (fasted state) for 28 consecutive days. The first dosing cycle will be followed by at least a 7-day off-treatment period (for PK analysis); however, no off-treatment period will be scheduled between subsequent treatment cycles. If individual subjects on GT0918 show an objective response or stable disease (SD) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria and who is expected to benefit from continued treatment in the opinion of the investigator, they may continue to receive additional cycles of GT0918 in the absence of untoward or serious toxicity; however, no subject is permitted to start a subsequent cycle after each bi-monthly disease evaluation until it is confirmed that disease progression has not occurred. A subject without disease progression may continue GT0918 treatment with the approval of the investigator; treatment can continue until a subject experiences an intolerable adverse event (AE) or disease progression, withdraws consent or until termination of the study by the sponsor. A total of 6 cycles of GT0918 is planned; however, subjects without progressive disease (PD) have the option to continue with their assigned dose in a 6-month Extension Study. At the end of total 6 cycles of GT0918 or additional extension cycles, a post-treatment period of 4 weeks will commence that concludes with an end-of-study visit.

The recommended Phase 2 dose (RP2D) will be based on the safety, tolerability, pharmacodynamic, and/or anti-tumor activities, etc. of GT0918 from the dose escalation stage.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 93 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Multi-Center, Open-Label, Two-Stage Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GT0918 in Subjects With Metastatic Castrate Resistant Prostate Cancer (mCRPC)
Actual Study Start Date : February 2016
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Phase 1 GT0918 level 1
generic name: not applicable dosage form: tablet dosage: oral dosage to be determined dosage frequency: daily dosage duration: 6 months
Drug: GT0918
anti-tumor activity
Other Names:
  • androgen receptor antagonist
  • proxalutamide

Primary Outcome Measures :
  1. dose-limiting toxicities (DLTs) [ Time Frame: 1 month ]
    abnormal laboratory value

  2. maximum tolerated dose (MTD),biological dose or minimal effective dose, (MED), and recommended Phase 2 dose(s) (RP2D). [ Time Frame: 1 month ]
    50 mg, 100 mg, 200 mg, 300 mg, 400 mg or 500 mg of GT0918

Secondary Outcome Measures :
  1. maximum concentration (Cmax) [ Time Frame: 6 months ]

  2. time that maximum concentration is observed (tmax) [ Time Frame: 6 months ]

  3. area under the concentration time-curve from time zero to infinity (AUC0∞) [ Time Frame: 6 months ]

  4. area under the plasma concentration-time curve from time zero hours to time (t hrs), (AUC0-t) [ Time Frame: 6 months ]

  5. area under the plasma concentration-time curve from time zero hours to 24 hours (AUC0-24) [ Time Frame: 6 months ]

  6. terminal elimination rate constant (λz) [ Time Frame: 6 months ]

  7. terminal elimination half life (t½) [ Time Frame: 6 months ]

  8. volume of distribution (Vz) [ Time Frame: 6 months ]

  9. volume of plasma cleared of the drug per unit time (C) [ Time Frame: 6 months ]

  10. circulating tumor deoxyribonucleic acid (ctDNA) [ Time Frame: 6 months ]
    antitumor activities

  11. circulating messenger ribonucleic acid (mRNA) [ Time Frame: 6 months ]
    antitumor activities

  12. circulating tumor cells (CTC) [ Time Frame: 6 months ]
    antitumor activities

  13. prostate-specific antigen (PSA) [ Time Frame: 6 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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. Histologically confirmed metastatic castrate resistant cancer (mCRPC) who progressed after both hormonal therapy (abiraterone or enzalutamide) and chemotherapy (docetaxel, for example); or cannot tolerate either or both of these classes of therapies.
  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 ongoing androgen deprivation or chemotherapy. Progressive disease is defined by 1 or more of the following criteria:

    • Subjects with a rising 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.
    • Subjects with measurable disease, progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
    • Subjects with metastatic bone disease, progression defined by 2 or more new lesions in a radionuclide bone scan.
  7. ECOG performance status of 0-2 (dose escalation phase); ECOG performance status of 0-1 (expansion phase).
  8. Screening blood counts of the following:

    • Absolute neutrophil count ≥ 1500/μL
    • Platelets ≥ 100,000/μL
    • Hemoglobin > 9 g/dL
  9. Screening chemistry values of the following:

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

Exclusion Criteria:

  1. Subjects with life expectancy less than 3 months.
  2. Discontinuation of bicalutamide or nilutamide less than 6 weeks, and other antiandrogens less than 4 weeks, abiraterone less than 3 weeks, prior to the start of study medication.
  3. Prior chemotherapy, radiation, sipuleucel-T or other experimental immunotherapy less than 4 weeks prior to the start of study medication.
  4. Prior chemotherapies more than 2 lines (Phase II part only) .
  5. Ongoing acute treatment-related toxicity associated with a previous therapy greater than grade 1 except for grade 2 alopecia or neuropathy.
  6. History of impaired adrenal gland function (eg, Addison's disease, Cushing's syndrome).
  7. Known gastrointestinal disease or condition that affects the absorption of GT0918.
  8. History of congestive heart failure New York Heart Association (NYHA) class III or IV or uncontrolled hypertension at screening.
  9. History or family history of long QT syndrome.
  10. History of other malignancy within the previous 3 years, except basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer.
  11. Use of systemic glucocorticoid (eg, prednisone, dexamethasone) within 14 days prior to the start of study medication.
  12. Co-administration of CYP3A4 ligands that serve as substrates or induce or inhibit the enzyme.
  13. Prior use of any herbal products known to decrease PSA levels (eg, PC-SPES or saw palmetto) within 30 days prior to the start of study medication.
  14. Major surgery within 30 days prior to the start of study medication.
  15. Blood transfusion (including blood products) within 1 week of screening.
  16. Serious persistent infection within 14 days prior to the start of study medication.
  17. Serious concurrent medical condition including CNS disorders.
  18. Previous history of difficulty swallowing capsules.
  19. Known hypersensitivity to GT0918 or its excipients.
  20. Any condition that, in the opinion of the investigator, would impair the subject's ability to comply with study procedures.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02826772

Layout table for location information
United States, Maryland
Chesapeake Urology Research Associates
Towson, Maryland, United States, 21204
United States, Nebraska
G U Research Network
Omaha, Nebraska, United States, 68130
United States, Nevada
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States, 89169
United States, New Jersey
Rutgers University
New Brunswick, New Jersey, United States, 08901
United States, New York
North Shore Hematology Oncology Associates
East Setauket, New York, United States, 11733
United States, Ohio
Gabrail Cancer Center Research
Canton, Ohio, United States, 44718
Sponsors and Collaborators
Suzhou Kintor Pharmaceutical Inc,
Layout table for investigator information
Study Director: Phoebe Zhang, PhD Suzhou Kintor Pharmaceuticals, Inc.

Layout table for additonal information
Responsible Party: Suzhou Kintor Pharmaceutical Inc, Identifier: NCT02826772    
Other Study ID Numbers: GT0918-US-1001
First Posted: July 11, 2016    Key Record Dates
Last Update Posted: July 29, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Androgen Receptor Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Androgen Antagonists
Hormone Antagonists