In this phase Ib/II study, participants with metastatic castration-resistant prostate cancer (mCRPC) who failed prior novel hormone therapy will be treated with XNW5004 in combination with enzalutamide.
This is a multicenter, phase Ib/II clinical trial, divided into three parts: The part1 is the dose escalation study of XNW5004 combined with Enzalutamide (Dose escalation in phase Ib) . The part2 is the dose expansion study of XNW5004 combined with Enzalutamide (Dose expansion in phase IIa). The phase Ib and IIa will evaluate the safety, tolerability and preliminary anti-tumor activity of XNW5004 in combination with enzalutamide to determine the recommended phase II dose (RP2D). The part3 is an open label, randomized phase 2 study (Phase IIb). The patients with mCRPC will be enrolled to assess the efficacy of XNW5004 at the RP2D in combination with Enzalutamide in comparison with Enzalutamide alone.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
307
Oral continuous
enzalutamide 160 mg (four 40 mg capsules) orally once daily
Cancer Hosipital of Shandong First Medical University,440 Jiyan Road, Jinan City, Shandong Province
Jinan, Shandong, China
RECRUITING270 Dongan Road, Shanghai
Shanghai, Shanghai Municipality, China
RECRUITINGPh Ib/IIa: Overall safety profile including adverse events
Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version \[5.0\])
Time frame: Baseline up to approximately 2 years
Ph Ib/IIa: Recommended phase 2 doses (RP2D) of XNW5004 in combination with enzalutamide
RP2D of XNW5004 as administered orally twice daily (BID), continuously in 28-day cycles, in combination with enzalutamide in subjects with mCRPC by safety data, pharmacokinetic data, pharmacodynamic data and efficacy data
Time frame: Approximately 6 months
Preliminary efficacy determination as evaluated by disease specific response criteria
Radiographic Progression-free survival(rPFS)was defined as the time from the date of first administration of the study drug to the date of radiographic progression base on the investigator assessment per PCWG3 criteria or death due to any cause (whichever comes first) in Phase IIa/IIb.
Time frame: Baseline until disease progression or death or through study completion (approximately 2 years)
Ph Ib/IIa: Pharmacokinetic Parameters
The area under the plasma concentration-time curve (AUC)
Time frame: The first 28-day cycle of therapy
Ph Ib/IIa: Pharmacokinetic Parameters
Maximum plasma concentration (Cmax)
Time frame: The first 28-day cycle of therapy
Ph Ib/IIa: Pharmacokinetic Parameters
Elimination half-life (t1/2)
Time frame: The first 28-day cycle of therapy
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Ph Ib/IIa: Pharmacokinetic Parameters
Time to maximum plasma concentration (Tmax)
Time frame: The first 28-day cycle of therapy
Ph Ib: Pharmacodynamic Parameters
The relative change from baseline in H3K27me3 (trimethylation at lysine 27 of histone H3)/ total histone H3.
Time frame: The first 28-day cycle of therapy
Overall Response Rate (ORR)
ORR was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). ORR was based on RECIST 1.1 response for patients with measurable disease at baseline reviewed by the investigator.
Time frame: Baseline up to approximately 2 years
Disease Control Rate (DCR)
DCR was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) according to RECIST v1.1 reviewed by the investigator.
Time frame: Baseline up to approximately 2 years
Evaluate overall survival
Overall Survival (OS) was defined as the time from the date of first administration to the date of death due to any cause.
Time frame: Baseline up to approximately 2 years
Proportion of patients with a PSA response at week 12
Proportion of patients with a PSA response (a decrease of PSA ≥ 50% compared to baseline) after 12 weeks of treatment, which need to be confirmed more than one time consecutively by PSA test with a minimum of 3 weeks time interval.
Time frame: Baseline up to approximately 2 years
Prostate-specific Antigen 50 (PSA50) Response
Proportion of patients with a PSA response greater than or equal to 50% throughout the entire treatment course.
Time frame: Baseline up to approximately 2 years
Time to first symptomatic skeletal event (SSE)
The time from the date of the first dose of study drug to the first occurrence of a SSE, including the use of external radiation therapy (EBRT) to prevent or alleviate bone symptoms, the occurrence of new symptomatic pathological fractures (vertebrae or non vertebrae), the occurrence of spinal cord compression, and tumor related orthopaedic surgical intervention, whichever comes first.
Time frame: Baseline up to approximately 2 years
Ph IIb:Overall safety profile including adverse events
Adverse Events will be graded by National Cancer Institute Common Terminology ACriteria for Adverse Events (NCI CTCAE version \[5.0\])
Time frame: Baseline up to approximately 2 years