Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06353386
Other study ID # 5684-01A
Secondary ID MK-5684-01A2023-
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date May 20, 2024
Est. completion date March 31, 2028

Study information

Verified date June 2024
Source Merck Sharp & Dohme LLC
Contact Toll Free Number
Phone 1-888-577-8839
Email Trialsites@merck.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Substudy 01A is part of a larger research study that is testing experimental treatments for metastatic castration-resistant prostate cancer (mCRPC). The larger study is the umbrella study (U01). The goal of substudy 01A is to evaluate the safety and efficacy of opevesostat-based treatment combinations, or as a single agent, in participants with mCRPC. This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for the opevesostat-based treatment combinations. There will be no hypothesis testing in this study.


Recruitment information / eligibility

Status Recruiting
Enrollment 220
Est. completion date March 31, 2028
Est. primary completion date March 31, 2028
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: The main inclusion criteria include but are not limited to the following: - Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate without small cell histology. - Prostate cancer progression and received androgen deprivation therapy (ADT) or post bilateral orchiectomy within 6 months before screening. - Evidence of disease progression from either, >4 weeks from last flutamide treatment, or >6 weeks from last bicalutamide or nilutamide treatment, if receiving first generation anti-androgen therapy as last treatment therapy. - Current evidence of metastatic disease. - Prior treatment with 1 to 2 novel hormonal agent(s) (NHA) for non-metastatic, or metastatic, hormone-sensitive prostate cancer or castration-resistant prostate cancer and have disease progression during or after treatment. - Treatment with bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for >4 weeks before randomization. - Participants who experienced adverse events (AEs) due to previous anticancer therapies must have recovered to <Grade 1 or baseline. - Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy. - Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load. - Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable. Exclusion Criteria: The main exclusion criteria include but are not limited to the following: - History of pituitary dysfunction. - Poorly controlled diabetes mellitus. - Active or unstable cardio/cerebro-vascular disease, including thromboembolic events. - History or family history of long corrected QT interval (QTc) syndrome. - Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or features suggestive of MDS/AML. - History or current condition of adrenal insufficiency. - History of (noninfectious) pneumonitis requiring steroids, or current pneumonitis. - HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. - Undergone major surgery, including local prostate intervention (except prostate biopsy) within 28 days before randomization, and has not recovered from the toxicities and/or complications. - Is on an unstable dose of thyroid hormone therapy within 6 months prior to first dose of study intervention. - Received a whole blood transfusion in the last 120 days before randomization (packed red blood cells and platelet transfusions are acceptable if not given within 28 days before randomization). - Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization. - Received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities, requiring corticosteroids. - Received a live or live-attenuated vaccine within 30 days before the first does of study intervention. Administration of killed vaccines is allowed. - Diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy, or any other form of immunosuppressive therapy, within 7 days prior to the first dose of study intervention. - Known additional malignancy that is progressing or has required active treatment within the past 3 years. - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. - Active autoimmune disease that has required systemic treatment in the past 2 years. - Active infection requiring systemic therapy. - Concurrent active HBV and HCV infections.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Opevesostat
Oral Tablet
Olaparib
Oral Tablet
Docetaxel
IV Infusion
Cabazitaxel
IV Infusion
Fludrocortisone acetate
Oral Tablet
Dexamethasone
Oral Tablet
Prednisone
Oral Tablet

Locations

Country Name City State
Australia Gallipoli Medical Research Ltd-GMRF CTU ( Site 0107) Greenslopes Queensland
Australia Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0110) Melbourne Victoria
Israel Rambam Health Care Campus-Oncology Division ( Site 1002) Haifa
Israel Rabin Medical Center ( Site 1001) Petah Tikva
Israel Sheba Medical Center ( Site 1000) Ramat Gan
Korea, Republic of Samsung Medical Center-Division of Hematology/Oncology ( Site 1501) Seoul
Taiwan China Medical University Hospital ( Site 1703) Taichung

Sponsors (2)

Lead Sponsor Collaborator
Merck Sharp & Dohme LLC Orion Corporation, Orion Pharma

Countries where clinical trial is conducted

Australia,  Israel,  Korea, Republic of,  Taiwan, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of participants who experience one or more dose-limiting toxicities (DLTs) The following events, if considered drug related by the investigator, will be considered a DLT: Grade 4 nonhematologic toxicity (not laboratory value); Grade 4 hematologic toxicity lasting >7 days, except thrombocytopenia (Grade 4 thrombocytopenia of any duration, Grade 3 thrombocytopenia associated with clinically significant bleeding); Any nonhematologic adverse event (AE) >Grade 3 in severity should be considered a DLT (with exceptions); Any Grade 3 or Grade 4 nonhematologic laboratory value (if certain criteria are met); Febrile neutropenia Grade 3 or Grade 4; Prolonged delay (>2 weeks) in initiating treatment after the first 28 days due to study intervention-related toxicity; Missing >25% of study intervention doses as a result of drug-related AE(s) during the first 28 days; Grade 5 toxicity. Up to approximately 28 days
Primary Number of participants who experience one or more adverse events (AEs) An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Up to approximately 46 months
Primary Number of participants who discontinue study intervention due to an AE An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Up to approximately 46 months
Primary Prostate-specific antigen (PSA) response rate The Prostate-specific Antigen (PSA) response rate is the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by =50%. The reduction in PSA level will be confirmed by an additional PSA evaluation performed =3 weeks from the original response per Prostate Cancer Working Group (PCWG) criteria. Up to approximately 46 months
Secondary Objective response rate (ORR) The ORR is defined as the percentage of participants with complete response (CR: disappearance of all target lesions per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1); and no evidence of disease (NED) on base scan per Prostate Cancer Working Group (PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG). ORR will be assessed by Blinded Independent Central Review (BICR). Up to approximately 46 months
Secondary Radiographic progression-free survival (rPFS) rPFS is defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 is =20% increase in the sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria is the appearance of =2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and are persistent for =6 weeks. rPFS will be assessed by BICR. Up to approximately 46 months
Secondary Overall survival (OS) OS is defined as the time from randomization to death due to any cause. Up to approximately 46 months
Secondary Duration of response (DOR) DOR is defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of a least 5 mm. PD per PCWG is the appearance of >2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and are persistent for >6 weeks. DOR will be assessed by BICR. Up to approximately 46 months
Secondary Time to first subsequent anticancer therapy (TFST) TFST is defined as the time from randomization to initiation of the first subsequent anticancer therapy or death, whichever occurs first. Up to approximately 46 months
Secondary Time to pain progression (TTPP) TTPP is defined as the time from randomization to pain progression based on the Brief Pain Inventory-Short Form (BPI-SF) Item 3 "worst pain in 24 hours" and by opiate analgesic use. Up to approximately 46 months
See also
  Status Clinical Trial Phase
Recruiting NCT04104776 - A Study of CPI-0209 in Patients With Advanced Solid Tumors and Lymphomas Phase 1/Phase 2
Withdrawn NCT03325127 - Outcomes of mCRPC Patients Treated With Ra-223 Concomitant With Abiraterone or Enzalutamide- A Chart Review Study
Withdrawn NCT02906605 - A Study of the Clinical Activity and Safety of JNJ-64041809, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Combination With Apalutamide Versus Apalutamide in Subjects With Metastatic Castration-resistant Prostate Cancer Phase 2
Recruiting NCT05743621 - Study of TVB-2640 in Men With Metastatic Castration-Resistant Prostate Cancer Phase 1
Completed NCT02204072 - BI836845 Plus Enzalutamide in Castrate Resistant Prostate Cancer (CRPC) Phase 1
Recruiting NCT05393791 - Phase II Randomised Controlled Trial of Patient-specific Adaptive vs. Continuous Abiraterone or eNZalutamide in mCRPC Phase 2
Completed NCT03927391 - Effect of a Reduced Dose Enzalutamide in Frail (m)CRPC Patients on Cognitive Side Effects Phase 4
Completed NCT02450812 - Non-interventional Study With Ra-223 Dichloride Assessing Overall Survival and Effectiveness Predictors for mCRPC Patients in a Real Life Setting in Germany
Active, not recruiting NCT03431350 - A Study of Niraparib Combination Therapies for the Treatment of Metastatic Castration-Resistant Prostate Cancer Phase 1/Phase 2
Active, not recruiting NCT03822845 - Evaluating the Clinical Accuracy of Gallium-68 PSMA PET/CT Imaging in Patients With Biochemical Recurrence of Prostate Cancer Phase 2/Phase 3
Completed NCT02162836 - A Safety Study of JNJ-56021927 in Participants With Metastatic Castration-Resistant Prostate Cancer Phase 1
Completed NCT02899104 - Navigant Study- Treatment Patterns in mCRPC (Metastatic Castrate Resistant Prostate Cancer )
Active, not recruiting NCT04381832 - Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer Phase 1/Phase 2
Completed NCT03563014 - A Local Retrospective Observational Study to Evaluate the Treatment Patterns of mCRPC Patients in Belgium Treated With Radium-223
Active, not recruiting NCT05968599 - A Study to Learn About the Study Medicines Called Enzalutamide and Abiraterone in People With Metastatic Castration-resistant Prostate Cancer
Active, not recruiting NCT02803437 - Drug Use Investigation of Xofigo, Castration Resistant Prostate Cancer With Bone Metastases
Recruiting NCT05944237 - HTL0039732 in Participants With Advanced Solid Tumours Phase 1/Phase 2
Withdrawn NCT03173859 - Efficacy of Rotations Between Abiraterone Acetate and Apalutamide in mCRPC Patients Phase 2
Terminated NCT02057666 - Study Of Tasquinimod In Asian Chemo-Naïve Patients With Metastatic Castrate-Resistant Prostate Cancer Phase 3
Active, not recruiting NCT04717154 - Ipilimumab With Nivolumab for Molecular-selected Patients With Castration-resistant Prostate Cancer Phase 2