A Study to Assess the Safety, Pharmacokinetics, and Anti-Tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer

Metastatic Castration-resistant Prostate Cancer Clinical Trial

Official title:

A Phase 1 Open-Label Study to Assess the Safety, Pharmacokinetics, and Anti-tumor Activity of Oral HP518 in Patients With Metastatic Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05252364
• Other study ID #: HP518-CS-001
• Status: Completed
• Phase: Phase 1
• Start date: December 14, 2021
• Est. completion date: January 22, 2024

Study information

• Verified date: March 2024
• Source: Hinova Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overall objective of this Phase 1 study is to evaluate the safety, PK, and anti-tumor activity of 12 weeks of daily oral dosing with HP518 after selecting the RP2D of HP518 based on assessments of multiple dose escalation in patients with progressive mCRPC.

Description:

This First in Human dose escalation and expansion study of HP518 in patients with mCRPC is being conducted not only to evaluate the safety and tolerability of orally administered HP518, but also to provide necessary information for efficacy analysis in future studies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: January 22, 2024
• Est. primary completion date: January 22, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Has histologically confirmed adenocarcinoma of the prostate.

2. Has metastatic disease at study entry documented by 2 or more bone lesions on bone scan or by soft tissue disease observed by CT/MRI.

3. Has disease progression while receiving any ADT, androgen biosynthesis inhibitors, or second-generation AR inhibitors.

4. Must have recovered from toxicities related to any prior treatments

5. Ongoing ADT with LHRH agonist/antagonist therapy or history of bilateral orchiectomy.

6. ECOG performance status score of 0 to 1.

Exclusion Criteria:

1. Has received more than 1 line of chemotherapy for prostate cancer.

2. Use of enzalutamide, and/or other second-generation AR inhibitors and/or abiraterone as follows:

• Received any agent within 4 weeks prior to the start of study drug.

• Discontinued agent without evidence of radiographic or PSA progression.

3. Has had any anticancer treatments, including immunotherapy, chemotherapy, or radiotherapy (eg, 177Lu-PSMA-617, radium 223, PARP inhibitor) within 4 weeks prior to the first dose of HP518.

4. Has gastrointestinal disorder affecting absorption (e.g., gastrectomy).

5. Has significant cardiovascular disease.

6. Use of an investigational agent, without evidence of radiographic or PSA progression, within 4 weeks prior to the first dose of HP518 or a period required by local regulation, whichever is longer.

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• HP518 - Dose Escalation
Part 1: Dose escalation Daily oral dosage with the prescribed dose level based on Cohort assignment.
• HP518 - Dose expansion
Part 2: Dose expansion Daily oral dosage with the highest dose with acceptable toxicity (RP2D) based on data from Part 1.

Locations

Country	Name	City	State
Australia	Border Medical Oncology	Albury	New South Wales
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Macquarie University	Macquarie Park	New South Wales
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Peter McCallum Cancer Center	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Hinova Pharmaceuticals Aus Pty Ltd

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidences of Protocol-defined DLT during the DLT assessment period , characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug	To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)	28 days
Primary	Incidence of Treatment-Emergent Adverse Events characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness	To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)	Through study completion, an average of 1 year
Primary	Incidence of laboratory abnormalities, characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing	To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)	Through study completion, an average of 1 year
Primary	Incidence of vital signs abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing	To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)	Time Frame: Through study completion, an average of 1 year
Primary	Incidence of ECG (PR, QRS, QT, and QTcF intervals) abnormalities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing	To evaluate the safety and tolerability and determine the MTD and the RP2D of orally administered HP518 (Part 1)	Through study completion, an average of 1 year
Primary	Proportion of patients showing a PSA decline of =50% between baseline and Week 12 of dosing with HP518.		12 weeks
Secondary	Assessment of pharmacokinetic parameters of HP518 : area under the concentration-time curve (AUC)		12 weeks
Secondary	Assessment of pharmacokinetic parameters of HP518: Maximum concentration (Cmax)		12 weeks
Secondary	Assessment of pharmacokinetic parameters of HP518: Time to maximum concentration (Tmax)		12 weeks
Secondary	Assessment of pharmacokinetic parameters of HP518: apparent terminal elimination half-life (T1/2)		12 weeks
Secondary	Assessment of pharmacokinetic parameters of HP518: apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)		12 weeks
Secondary	Assessment of pharmacokinetic parameters of HP518: oral clearance (CL/F)		12 weeks
Secondary	Assessment of PSA50 from baseline to after 4 and 8 weeks of dosing with HP518	To evaluate PSA50 from baseline to after 4 and 8 weeks of dosing with HP518	8 weeks
Secondary	Time to PSA progression using the PCWG3 definition (PSA >25% and >2 ng/mL above nadir, confirmed by progression at 2 time points at least 3 weeks apart)	To evaluate the time to PSA progression	Through study completion, an average of 1 year
Secondary	Time to radiographic progression using the RECIST v1.1 and PCWG3 definition	To evaluate radiographic progression per RECIST v1.1 and PCWG3	Through study completion, an average of 1 year
Secondary	Radiographic response measured by RECIST 1.1 in patients with measurable soft tissue disease at baseline	To assess objective response by RECIST v1.1 (proportion of patients with a PR or CR) in patients with measurable soft tissue disease at baseline	Through study completion, an average of 1 year
Secondary	Change in number of AR N-term-positive CTCs/ml from baseline to week 12		12 weeks
Secondary	Genomic profiling using cfDNA		12 weeks