A Study of ZEN003694 in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02711956|
Recruitment Status : Completed
First Posted : March 17, 2016
Results First Posted : August 10, 2021
Last Update Posted : November 30, 2021
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Castration-Resistant Prostate Cancer||Drug: ZEN003694 Drug: Enzalutamide||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||75 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b/2a Safety and Tolerability Study of ZEN003694 in Combination With Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer|
|Actual Study Start Date :||December 2016|
|Actual Primary Completion Date :||November 2019|
|Actual Study Completion Date :||November 2019|
Experimental: DE and DC - ZEN003694 in Combination with Enzalutamide
Dose Escalation (DE) and Dose Confirmation (DC): ZEN003694 will be administered orally once daily with enzalutamide in 28-day cycles, enrolling mCRPC patients.
Two patient populations will be enrolled in DE and DC. Cohort A: Patients with prior progression on enzalutamide or apalutamide by PCWG2 criteria who were receiving a stable dose of enzalutamide at the time of study entry. Cohort B: Patients who were enzalutamide-naïve with prior progression on abiraterone by Prostate Cancer Working Group 2 (PCWG2) criteria.
- For Dose Escalation: Incidence of Dose-limiting Toxicities (DLT) to Determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of ZEN003694 in Combination With Enzalutamide. [ Time Frame: Cycle 1 (Day 1 thru Day 28) ]Determination of DLT was made during the first 28 days of treatment in the dose escalation phase. A DLT is defined as a clinically significant AE or laboratory abnormality that is considered possibly, probably, or definitely related to study drug. The MTD reflects the highest dose of ZEN003694 in combination with enzalutamide that did not cause a DLT in more than 1 of 6 patients. The RP2D is the recommended dose of ZEN003694 in combination with enzalutamide as determined in the dose confirmation phase of the study.
- For Dose Escalation and Dose Confirmation: Incidence of Treatment-emergent Adverse Events (TEAE) and Treatment-related Serious Adverse Events (SAE) [ Time Frame: Cycle 1 Day 1 to 30 days post last dose ]Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity of AEs was graded based on the National Cancer Institute's Common Terminology for Adverse Events (V4.03). A serious adverse event (SAE) was any AE that was: fatal; life-threatening; required in-patient hospitalization or prolonged an existing hospitalization; disabling or incapacitating; a congenital anomaly or birth defect; or any other important medical event.
- Evaluate Prostate-specific Antigen (PSA) Response Rate by PCWG2 Criteria [ Time Frame: Screening up to 35 months ]The PSA response rate will be evaluated using PCWG2 criteria and defined as the proportion of patients with a PSA decline of at least 50%. Any change from baseline is confirmed by a second measurement at least 3 weeks later. PSA Response Rate will be evaluated using PCWG2 criteria and defined as following: Percentage change from baseline in PSA to 12 weeks post ZEN003694 dose. Only evaluate for patients with at least 12 weeks of treatment, the PSA assessment at 12 weeks (84 days +/-3 days) will be used; Maximum percent decrease in PSA from baseline that occurs at any point after treatment. Evaluable for all patients with post-baseline PSA. Arms will be combined to analyze efficacy in Cohort A and Cohort B.
- Evaluate Radiographic Response Rate (Overall Response Rate) by PCWG2 Criteria [ Time Frame: Screening up to 35 months ]Tumor response will be evaluated using the PCWG2 criteria. Patients with measurable disease will be evaluated for clinical benefit as determined by tumor response using RECIST v1.1. Patients with non-measurable bone disease will be evaluated for progression based on the presence of any new lesions by bone scans. Radiographic tumor evaluation will be performed at screening and every 3 cycles or more frequently as determined by the investigator. Using the tumor response that is determined by the investigator, best overall response will be determined using RECIST v1.1. Best overall response is defined as the best response recorded from the start of treatment until disease progression or study exit. Arms will be combined to analyze efficacy in Cohort A and Cohort B.
- Evaluate Overall Median Progression-free Survival by PCWG2 Criteria [ Time Frame: Screening up to 35 months ]Overall progression free survival (PFS) is determined using the PCWG2 criteria. Overall PFS is measured from screening until the time that disease progression (radiographic progressive disease or clinical deterioration) or death is documented, whichever occurs first. Arms will be combined to analyze efficacy in Cohort A and Cohort B.
- Evaluate Median Radiographic Progression-Free Survival by PCWG2 Criteria [ Time Frame: Screening up to 35 months ]Radiographic progression-free survival (rPFS) is determined using the PCWG2 criteria to assess both soft-tissue and bone assessments. The rPFS is measured from screening until the time the first radiographic scan shows disease progression, or until the time of death, whichever occurs first. If radiographic disease progression is identified at the first on-treatment radiographic assessment at Cycle 3 Day 1 (8 weeks), radiographic progression must be confirmed by a second assessment 6 or more weeks later. Patients who do not progress radiographically or did not die prior to study exit are censored on the date of their last dose of ZEN003694. Arms will be combined to analyze efficacy in Cohort A and Cohort B.
- Measure the Pharmacokinetic (PK) Parameter: AUC(0-24h) of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide. [ Time Frame: Cycle 1 Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 1 Day 2: pre-dose; Cycle 1 Day 15: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose ]AUC(0-24h) is defined as the area under the curve (plasma concentration of drug over a 24-hour time period).
- Measure the Pharmacokinetic (PK) Parameter: Cmax of ZEN003694 and ZEN003791 (Active Metabolite) Administered in Combination With Enzalutamide [ Time Frame: Cycle 1 Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose; Cycle 1 Day 2: pre-dose; Cycle 1 Day 15: pre-dose, 0.25, 0.5, 1, 2, 4, 6 and 8 hours post-dose ]Cmax is defined as the maximum or peak plasma concentration of drug.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02711956
|United States, California|
|University of California Los Angeles Medical Center|
|Los Angeles, California, United States|
|University of California San Francisco Medical Center|
|San Francisco, California, United States|
|United States, Michigan|
|Karmanos Cancer Institute|
|Detroit, Michigan, United States|
|Karmanos Cancer Institute|
|Farmington Hills, Michigan, United States|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States|
|Weill Cornell Medicine - New York Presbyterian|
|New York, New York, United States|
|United States, Oregon|
|Oregon Health & Science University|
|Portland, Oregon, United States|
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States|