A Phase 1 Trial of SHR3680 With or Without SHR3162 in Prostate Cancer

Phase 1

Completed

• Conditions: Neoplasm; Prostate Cancer
• Interventions: Drug: SHR3680; SHR3162

• Registration Number: NCT02747342
• Lead Sponsor: Atridia Pty Ltd.

Brief Summary

This is a multicenter, dose-escalation/expansion phase 1 trial to evaluate the safety, tolerability and efficacy of SHR3680 with or without SHR3162 given orally to subjects with metastatic castration-resistant prostate cancer (mCRPC).

Detailed Description

This study consists of 2 Part. In the Part 1 (dose escalation phase), up to 4 dose levels of SHR3680 will be investigated with a sequential "3+3" design (3 or 6 participants in each dose level). There will be a single-dose pharmacokinetic (PK) run-in period (7 days). Following the first dose, participants will enter a 1 week treatment-free period to evaluate safety and single-dose PK. If not dose-limiting toxicities (DLTs) are observed during the 1-week period, SHR3680 administration will resume at the same dose level.

In the Part 2a (expansion phase), up to 9 additional participants will be enrolled at the MTD or recommended phase 2 dose (RP2D). The purpose of the expansion part of the study is to explore the clinical benefits of SHR3680 and to further identify its PK features.

In Part 2b (combination phase), two dose cohorts of SHR3162 combine with SHR3680 at fixed dose will be investigated.

Study Timeline

• Study First Submitted: 2016-04-19
• Study First Submitted QC: 2016-04-20
• Study First Posted: 2016-04-21
• Study Start: 2016-09
• Primary Completion: 2019-06-28
• Study Completion: 2020-06-28
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-20
• Last Update Posted: 2020-07-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 33

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SHR3680; SHR3680+SHR3162	SHR3680; SHR3162	In dose esclation and expansion phase, SHR3680 will be administered orally In combination phase, SHR3680 will be administered together with SHR3162

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD)	4 weeks	MTD is defined as the maximum dose level at which no more than 1 out of 3 participants experience a DLT within the first 4 weeks of multiple dosing
Recommended Phase 2 doses (RP2Ds)	24 months	RP2D will be determined based on the available data for toxicity and PK.

Secondary Outcome Measures

Name	Time	Method
The cMax (peak plasma concentration) of SHR3680 and SHR3162	4 weeks	The cMax (peak plasma concentration) of SHR3680 given as BID 240 mg tablets in combination with SHR3162
PSA reduction	12 weeks	Percentage of participants reaching at least a 50% reduction in prostate specific antigen (PSA) at Week 12 as compared to baseline
The AUC of SHR3680 and SHR3162 (area under the curve)	4 weeks	The AUC of SHR3680 given as BID 240 mg tablets in combination with SHR3162
Number of participants with treatment-emergent adverse events	24 months	The number and proportion of subjects experiencing treatment-emergent AEs (TEAE); drug exposure; clinically significant changes in laboratory parameters, vital signs, physical examinations, weight, ECOG performance status, ECG abnormalities, number and causes of deaths.
PSA progression	24 months	Time to reach the PSA Progression
Radiological progression-free survival (PFS)	24 months	the length of time during and after the treatment
Objective response rate (ORR)	24 months	the proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time periodthe proportion of patients with tumor size reduction of a predefined amount and for a minimum time period

Trial Locations

Locations (6)

Westmead Hospital; 🇦🇺 Sydney, New South Wales, Australia

Border Medical Oncology; 🇦🇺 Albury, New South Wales, Australia

St George Hospital; 🇦🇺 Kogarah, New South Wales, Australia

Chris O'Brien Lifehouse; 🇦🇺 Camperdown, New South Wales, Australia

Icon Cancer Centre; 🇦🇺 South Brisbane, Queensland, Australia

Liverpool Hospital; 🇦🇺 Liverpool, New South Wales, Australia