Clinical trial NCT03414034: Onvansertib in Combination With Abiraterone and Prednisone in Adult Patients With Metastatic Castration-Resistant Prostate Cancer
Official title: A Phase 2 Study of PCM-075 (Onvansertib) in Combination With Abiraterone and Prednisone in Adult Patients With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Castration-Resistant Prostate Cancer
Keywords: PLK1
PLK Inhibitor
Onvansertib
Lead sponsor: Cardiff Oncology
Sponsor class: INDUSTRY
First posted: 2018-01-29
Enrollment: 72
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Males ≥ 18 years of age on the day of consenting to the study.
2. Ability to swallow the study drug as a whole tablet.
3. 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.
4. Asymptomatic or minimally symptomatic disease.
5. Metastatic disease by bone scan or other nodal or visceral lesions on CT or MRI at any time (past or present).
6. Participant currently receiving abiraterone and prednisone for CRPC.
7. 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.
8. 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.
9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
10. 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:

1. Major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery.
2. Rapidly progressive symptoms of mCRPC.
3. Acute neurological dysfunction as a result of bone metastasis.
4. Previously treated with enzalutamide or experimental therapies directed against androgen receptor (ie, apalutamide).
5. 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.
6. 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.
7. Treatment with any of the drugs listed in Section 8.4.5 at the time of study treatment initiation.
8. 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.
9. New York Heart Association (NYHA) Class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition, or hypertensive or metabolic condition.
10. Myocardial infarction in the previous 12 weeks (from the start of treatment)
11. 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.
12. Planned concomitant use of medications known to prolong the QT/QTc interval
13. Presence of risk factors for torsade de pointes, including family history of Long QT Syndrome or uncorrected hypokalemia.

Primary outcomes:
measure: Percentage of Participants Achieving Disease Control at or Before 12 Weeks
timeFrame: Baseline up to Week 12
Secondary outcomes:
measure: Mean Percentage Change From Baseline in PSA at 12 Weeks
timeFrame: Baseline and Week 12
measure: Mean Absolute Change From Baseline in PSA at 12 Weeks
timeFrame: Baseline and Week 12
measure: Median Percentage Change From Baseline in PSA at 12 Weeks
timeFrame: Baseline and Week 12
measure: Median Absolute Change From Baseline in PSA at 12 Weeks
timeFrame: Baseline and Week 12
measure: Time to PSA Progression or Death
timeFrame: Up to approximately 100 weeks
measure: Time to Radiographic Progression or Death
timeFrame: Up to approximately 110 weeks
measure: Percentage of Participants Achieving Radiographic Responses at or Before 12 Weeks
timeFrame: Baseline up to Week 12
measure: Percentage of Participants Who Are Adherent to Study Treatment (PP Analysis) Achieving Disease Control at or Before 12 Weeks
timeFrame: Baseline up to Week 12
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 27 months
measure: Number of Participants With DLTs
timeFrame: Arms A and B: up to one 21-day cycle; Arm C: up to two 14-day cycles
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
References:
citation: Hagege A, Ambrosetti D, Boyer J, Bozec A, Doyen J, Chamorey E, He X, Bourget I, Rousset J, Saada E, Rastoin O, Parola J, Luciano F, Cao Y, Pages G, Dufies M. The Polo-like kinase 1 inhibitor onvansertib represents a relevant treatment for head and neck squamous cell carcinoma resistant to cisplatin and radiotherapy. Theranostics. 2021 Sep 21;11(19):9571-9586. doi: 10.7150/thno.61711. eCollection 2021.