A Study Evaluating Tolerability, Pharmacokinetics, and Preliminary Efficacy of HC-1119 in Patients.

A Phase I Study Evaluating Tolerability, Pharmacokinetics, and Preliminary Efficacy of HC-1119 in Patients With Metastatic Castration-Resistant Prostate Cancer.

This is a phase I study evaluating tolerability, pharmacokinetics, and preliminary efficacy of HC-1119 in patients with metastatic castration-resistant prostate cancer. The study objective is to study the tolerability, safety, and dose-limiting toxicities (DLT) of HC-1119 in patients with mCRPC.

Study Overview

• Status: Completed
• Conditions: Metastatic Castration Resistant Prostate Cancer
• Intervention / Treatment: Drug: HC-1119

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Hinova Pharmaceuticals Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria (those who meet all of the following are eligible):

1. Voluntarily participated in the study, with understanding of relevant study procedures and signed informed consent form;
2. Male , ≥18 years old;
3. With histologically or cytologically confirmed prostate cancer, without neuroendocrine carcinoma or ductal adenocarcinoma;
4. With evidence of metastatic disease (such as bone scan and CT/MRI results);
5. Patients with relapsed, refractory, or progressive disease despite castration (surgery or chemical) or combined androgen deprivation therapy (Progressive disease is defined as 1 or more of the following 3 criteria: Serum PSA progression: A minimum of 3 rising PSA values with an interval of at least 1 week between determinations, resulting in a final value higher than 50% of the minimum, with a starting PSA value > 2 ng/ml; Soft tissue disease progression as defined by RECIST 1.1; Bone disease progression defined by PCWG2 with 2 or more new metastatic lesions on bone scan);
6. Castrate levels of testosterone (< 50 ng/dl) at screening;
7. Bilateral orchiectomy or ongoing androgen deprivation therapy with effective GnRH analogues;
8. Estimated life expectancy > 6 months;
9. ECOG performance status ≤ 1;

10. Laboratory tests must meet the following criteria:

    1. Routine Blood Test: hemoglobin (Hb) ≥ 90 g/L (no blood transfusion within the last 14 days); absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelet count (PLT) ≥ 80 x 109/L;
    2. Blood Biochemistry: creatinine (Cr) ≤ 2 x upper limit of normal (ULN), or Cr > 2 x ULN but the calculated CrCl ≥ 60 mL/min; bilirubin (BIL) ≤ 2 x ULN; alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤ 2.5 x ULN (or ≤ 5.0 x ULN for patients with liver metastases);
    3. Coagulation: INR < 1.5.

Exclusion Criteria (those who meet any one of the following are ineligible):

1. Ongoing toxicity ( ≥ Grade 2 toxicity) from previous treatments;
2. Clinically significant GI dysfunction which may affect the intake, transport, or absorption of drug (such as inability to swallow, chronic diarrhea, and bowel obstruction, etc.), or patients with complete gastrectomy;
3. History of allergies, or known hypersensitivity to components of the investigational drug;
4. Brain metastases;
5. Other malignancies within the last 5 years (except for curatively treated non-melanoma skin cancer);
6. History of organ transplants
7. HIV seropositive;
8. Past medical history of seizures or serious CNS diseases;
9. History of unexplained coma;
10. Family history of seizures;
11. History of traumatic brain injury;
12. History of medication or drug abuse;
13. Patients with severe cardiovascular diseases, including those with myocardial infarction, arterial thrombosis, unstable angina, or clinical symptomatic heart failure within the past 6 months;
14. Uncontrolled hypertension (systolic ≥ 160 mmHg or diastolic ≥ 100 mmHg). Patients with a history of hypertension is eligible if his blood pressure is controlled with antihypertensives;
15. Medications that lower the seizure threshold must be used during the study;
16. Treatment with 5α-reductase inhibitors (finasteride, dutasteride), estrogen, or cyproterone within the past 4 weeks;
17. Treatment with ketoconazole within the past 4 weeks;
18. Previously treated with investigational or approved medications that inhibit testosterone synthesis (such as abiraterone acetate, TAK-683, and TAK-448) or target testosterone receptors (such as enzalutamide, SHR3680, proxalutamide, and ARN509);
19. Participated in other clinical trials within 1 month prior to enrollment;
20. Subjects is determined by the investigator to be unsuitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dose group; Drug name L:HC-1119 Dosage: 40 mg, 80 mg, 160 mg, and 200 mg	Drug: HC-1119; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicities(DLT)	Safety measures	From the first dose of the study to the 12th week after dose
Number of patients with adverse events	Safety measures	From the first dose of the study to the 12th week after dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum drug concentration(Cmax)	Single-dose and repeated-dose	From the first dose of the study to the 12th week after dose
Time of maximum drug concentration(Tmax)	Single-dose and repeated-dose	From the first dose of the study to the 12th week after dose
Area under curve from time 0 to 24h (AUC0-24h)	Single-dose and repeated-dose	From the first dose of the study to the 12th week after dose
Maximal PSA Response Rate	Percentage of patients with > 50% decrease in PSA levels from baseline during the 12-week treatment period	From the first dose of the study to the 12th week after dose
Response rate of prostate specific antigen (PSA)	Percentage of patients with > 50% decrease in PSA levels from baseline at weeks 6, 8, 10, and 12.	From the first dose of the study to the 12th week after dose

Collaborators and Investigators

• Sponsor: Hinova Pharmaceuticals Inc.
• Collaborators: West China Hospital
• Investigators: Principal Investigator: Feng Bi, professor, West China Hospital; Principal Investigator: Li Zheng, professor, West China Hospital

Publications and helpful links

General Publications

• Li X, Cheng K, Li X, Zhou Y, Liu J, Zeng H, Chen Y, Liu X, Zhang Y, Wang Y, Bi F, Zheng L. Phase I clinical trial of HC-1119: A deuterated form of enzalutamide. Int J Cancer. 2021 Oct 1;149(7):1473-1482. doi: 10.1002/ijc.33706. Epub 2021 Jul 7.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2017
• Primary Completion (Actual): September 26, 2018
• Study Completion (Actual): August 28, 2019

Study Registration Dates

• First Submitted: December 11, 2018
• First Submitted That Met QC Criteria: December 11, 2018
• First Posted (Actual): December 12, 2018

Study Record Updates

• Last Update Posted (Actual): November 3, 2020
• Last Update Submitted That Met QC Criteria: October 30, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: HC-1119-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No