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

NCT02826772 | Completed Phase 1

• 1 other identifier: GT0918-US-1001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 6

Brief Summary

This was a Phase 1, multicenter, open-label, clinical trial in adult subjects with metastatic castrate resistant prostate cancer who progressed after both hormonal therapy (abiraterone or enzalutamide) and chemotherapy (docetaxel), or cannot tolerate either or both therapies. The study involved a Phase 1 dose escalation of oral GT0918 to evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics.

Conditions

Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Outcome Measures

Primary Outcomes (2)

• dose-limiting toxicities (DLTs)

  abnormal laboratory value

  1 month

• maximum tolerated dose (MTD),biological dose or minimal effective dose, (MED), and recommended Phase 2 dose(s) (RP2D).

  50 mg, 100 mg, 200 mg, 300 mg, 400 mg or 500 mg of GT0918

  1 month

Secondary Outcomes (13)

• maximum concentration (Cmax)

  6 months

• time that maximum concentration is observed (tmax)

  6 months

• area under the concentration time-curve from time zero to infinity (AUC0∞)

  6 months

• area under the plasma concentration-time curve from time zero hours to time (t hrs), (AUC0-t)

  6 months

• area under the plasma concentration-time curve from time zero hours to 24 hours (AUC0-24)

  6 months

Study Arms (1)

Phase 1 GT0918 level 1

EXPERIMENTAL

generic name: not applicable dosage form: tablet dosage: oral dosage to be determined dosage frequency: daily dosage duration: 6 months

Drug: GT0918

Interventions

GT0918 DRUG

anti-tumor activity

Also known as: androgen receptor antagonist, proxalutamide

Phase 1 GT0918 level 1

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained prior to any study-related procedure being performed.
• Subjects at least 18 years of age or older at the time of consent.
• 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.
• 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.
• Metastatic disease documented by computed tomography (CT)/magnetic resonance imaging (MRI) or bone scan.
• 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.
• ECOG performance status of 0-2 (dose escalation phase); ECOG performance status of 0-1 (expansion phase).
• Screening blood counts of the following:
• Absolute neutrophil count ≥ 1500/μL
• Platelets ≥ 100,000/μL
• Hemoglobin \> 9 g/dL
• Screening chemistry values of the following:

You may not qualify if:

• Subjects with life expectancy less than 3 months.
• 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.
• Prior chemotherapy, radiation, sipuleucel-T or other experimental immunotherapy less than 4 weeks prior to the start of study medication.
• Prior chemotherapies more than 2 lines (Phase II part only) .
• Ongoing acute treatment-related toxicity associated with a previous therapy greater than grade 1 except for grade 2 alopecia or neuropathy.
• History of impaired adrenal gland function (eg, Addison's disease, Cushing's syndrome).
• Known gastrointestinal disease or condition that affects the absorption of GT0918.
• History of congestive heart failure New York Heart Association (NYHA) class III or IV or uncontrolled hypertension at screening.
• History or family history of long QT syndrome.
• History of other malignancy within the previous 3 years, except basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer.
• Use of systemic glucocorticoid (eg, prednisone, dexamethasone) within 14 days prior to the start of study medication.
• Co-administration of CYP3A4 ligands that serve as substrates or induce or inhibit the enzyme.
• 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.
• Major surgery within 30 days prior to the start of study medication.
• Blood transfusion (including blood products) within 1 week of screening.

Sponsors & Collaborators

• Suzhou Kintor Pharmaceutical Inc,: lead

Study Sites (6)

Chesapeake Urology Research Associates

Towson, Maryland, 21204, United States

Location

G U Research Network

Omaha, Nebraska, 68130, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Rutgers University

New Brunswick, New Jersey, 08901, United States

Location

North Shore Hematology Oncology Associates

East Setauket, New York, 11733, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

Related Publications (1)

• Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.

  PMID: 32203306 DERIVED

MeSH Terms

Interventions

proxalutamide; Androgen Receptor Antagonists

Intervention Hierarchy (Ancestors)

Androgen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Phoebe Zhang, PhD

  Suzhou Kintor Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2016
• First Posted: July 11, 2016
• Study Start: February 10, 2016
• Primary Completion: May 15, 2019
• Study Completion: February 15, 2020
• Last Updated: March 17, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)