Onvansertib in Combination With Abiraterone and Prednisone in Adult Patients With Metastatic Castration-Resistant Prostate Cancer

Study Overview
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Brief Summary
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The purpose of the phase 2 study is to determine whether Onvansertib is safe and tolerable in adult participants with Metastatic Castration-Resistant Prostate Cancer who have disease progression while receiving abiraterone acetate (abiraterone) and prednisone therapy, and to observe the effects of Onvansertib in combination with abiraterone and prednisone on disease control.

Official Title
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A Phase 2 Study of PCM-075 (Onvansertib) in Combination With Abiraterone and Prednisone in Adult Patients With Metastatic Castration-Resistant Prostate Cancer

Conditions
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Metastatic Castration-Resistant Prostate Cancer

Intervention / Treatment
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* Drug: Onvansertib
* Drug: Abiraterone
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males ≥ 18 years of age on the day of consenting to the study. Ability to swallow the study drug as a whole tablet. Histologically confirmed prostate adenocarcinoma without significant small- cell/neuroendocrine or other variant histologies, with rising PSA and/or radiographic progression in the setting of castration-level testosterone (< 50 ng/dL) indicating mCRPC. Participants must have either undergone surgical castration or continue on GnRH agonist/antagonist on the appropriate schedule throughout the study period. Asymptomatic or minimally symptomatic disease. Metastatic disease by bone scan or other nodal or visceral lesions on CT or MRI at any time (past or present). Participant currently receiving abiraterone and prednisone for CRPC. Participant has been on abiraterone for castration-sensitive prostate cancer (CSPC) or castration-resistant prostate cancer (CRPC). Participants who have received abiraterone for CSPC must have had a response to hormonal therapy, as defined by any decline in PSA, radiographic response and/or clinical benefit after starting hormonal therapy. Participants who have received abiraterone for CRPC must have responded to abiraterone, defined by any decline in PSA, radiographic response, and/or clinical benefit after starting abiraterone. Two rising PSA values separated by at least 1 week, one showing a rise of at least 0.3 ng/mL and one confirmatory value not showing a decline, while on abiraterone therapy. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Participant has adequate bone marrow and organ function as shown by: Absolute neutrophil count (ANC) ≥ 1.0 x 109/L Platelets ≥ 100 x 10^9/L Hemoglobin (Hgb) ≥ 9.0 g/dL Serum creatinine ≤ 2 x the upper limit of normal (ULN) Total serum bilirubin ≤ 1.5 x ULN (in participants with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x ULN (or ≤ 5.0 x ULN if hepatic metastases are present) Exclusion Criteria: Major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery. Rapidly progressive symptoms of mCRPC. Acute neurological dysfunction as a result of bone metastasis. Previously treated with enzalutamide or experimental therapies directed against androgen receptor (ie, apalutamide). Use of any chemotherapy, investigational agents, immunotherapy, or hormonal therapy other than GnRH agonists within 28 days of the start of treatment on protocol. Use of bone targeted agents including bisphosphonates and RANK ligand inhibitors is allowed if on stable dose; Xgeva or Zometa cannot be started within 28 days of initiating study therapy. Systemic corticosteroids except as part of on label treatment prostate cancer regimens. Note: Topical applications (eg, rash), inhaled sprays (eg, obstructive airways diseases), eye drops or local injections (eg, intra-articular) are allowed. Treatment with any of the drugs listed in Section 8.4.5 at the time of study treatment initiation. Has received wide field radiotherapy (including therapeutic radioisotopes such as radium 223) ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study drug or has not recovered from side effects of such therapy. New York Heart Association (NYHA) Class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition, or hypertensive or metabolic condition. Myocardial infarction in the previous 12 weeks (from the start of treatment) QT interval with Fridericia's correction [QTcF] >470 milliseconds. The QTcF should be calculated as the arithmetic mean of the QTcF on triplicate ECGs. In the case of potentially correctible causes of QT prolongation (e.g., medications, hypokalemia), the triplicate ECG may be repeated once during screening and that result may be used to determine eligibility. Planned concomitant use of medications known to prolong the QT/QTc interval Presence of risk factors for torsade de pointes, including family history of Long QT Syndrome or uncorrected hypokalemia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: onvansertib + abiraterone and prednisone<br>On Day 1 of each cycle, onvansertib will be administered orally (PO) once daily (QD) at a dose of 24 mg/m^2 for 5 days (Day 1 through Day 5) out of a 21-day cycle. Beginning on Day 1 and continuing uninterrupted throughout each cycle, participants will also receive abiraterone and prednisone. This arm was discontinued. | Drug: Onvansertib<br>* Onvansertib orally<br>* Other names: PCM-075;Drug: Abiraterone<br>* Abiraterone orally<br>Drug: Prednisone<br>* Prednisone orally<br>|
| Experimental: Arm B: onvansertib + abiraterone and prednisone<br>On Day 1 of each cycle, onvansertib will be administered orally (PO) once daily (QD) at a dose of 24 mg/m^2 for 5 days (Day 1 through Day 5) out of a 14-day cycle. Beginning on Day 1 and continuing uninterrupted throughout each cycle, participants will also receive abiraterone and prednisone. | Drug: Onvansertib<br>* Onvansertib orally<br>* Other names: PCM-075;Drug: Abiraterone<br>* Abiraterone orally<br>Drug: Prednisone<br>* Prednisone orally<br>|
| Experimental: Arm C: onvansertib + abiraterone and prednisone<br>On Day 1 of each cycle, onvansertib will be administered orally (PO) once daily (QD) at a dose of 12 mg/m^2 for 14 days (Day 1 through Day 14) out of a 21-day cycle. Beginning on Day 1 and continuing uninterrupted throughout each cycle, participants will also receive abiraterone and prednisone. | Drug: Onvansertib<br>* Onvansertib orally<br>* Other names: PCM-075;Drug: Abiraterone<br>* Abiraterone orally<br>Drug: Prednisone<br>* Prednisone orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Lack of Prostate-specific Antigen (PSA) Progression per Prostate Cancer Working Group 3 (PCWG3) Criteria After 12 Weeks |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change from Baseline in PSA at 12 Weeks |  | Baseline and Week 12 | 
| Maximal Percentage Change from Baseline in PSA |  | Baseline up to 20 months | 
| Absolute Change from Baseline in PSA Response |  | Baseline up to 20 months | 
| Time to PSA Progression per PCWG3 criteria |  | Baseline up to 20 months | 
| Time to Radiographic Progression per PCWG3 criteria |  | Baseline up to 20 months | 
| Radiographic Response per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) |  | Baseline up to 20 months | 
| Percentage of Participants Who are Adherent to Study Treatment (Per-Protocol Analysis) With Lack of Prostate-specific Antigen (PSA) Progression per Prostate Cancer Working Group 3 (PCWG3) Criteria After 12 Weeks |  | Week 12 | 
| Number of Participants With Adverse Events per Common Terminology Criteria for Adverse Events (CTCAE) |  | Baseline up to 30 days after last dose of study drug (Up to 20 months) | 
| Number of Participants With Dose Limiting Toxicity (DLT) | DLT is defined as a hematologic adverse event (AE) of Grade ≥ 3 or nonhematologic AE of Grade ≥ 3 considered related to the study drug(s). | Up to 20 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PLK1, PLK Inhibitor, Onvansertib