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

NCT ID: NCT03774056

Last Updated: 2020-11-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-10
• Study Completion Date: 2019-08-28

Brief Summary

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.

Conditions

Metastatic Castration Resistant Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

dose group

Drug name L:HC-1119 Dosage: 40 mg, 80 mg, 160 mg, and 200 mg

Group Type: EXPERIMENTAL

HC-1119

Intervention Type: DRUG

oral

Interventions

HC-1119

oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

West China Hospital

OTHER

Sponsor Role: collaborator

Hinova Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Feng Bi, professor

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Li Zheng, professor

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

Hinova Pharmaceuticals Inc.

Chengdu, Sichuan, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 34109624 (View on PubMed)

Other Identifiers

HC-1119-01

Identifier Type: -

Identifier Source: org_study_id