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

NCT ID: NCT03414034

Last Updated: 2024-11-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-14
• Study Completion Date: 2023-10-16

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.

Conditions

Metastatic Castration-Resistant Prostate Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: onvansertib + abiraterone and prednisone

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.

Group Type: EXPERIMENTAL

Onvansertib

Intervention Type: DRUG

Onvansertib orally

Abiraterone

Intervention Type: DRUG

Abiraterone orally

Prednisone

Intervention Type: DRUG

Prednisone orally

Arm B: onvansertib + abiraterone and prednisone

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.

Group Type: EXPERIMENTAL

Onvansertib

Intervention Type: DRUG

Onvansertib orally

Abiraterone

Intervention Type: DRUG

Abiraterone orally

Prednisone

Intervention Type: DRUG

Prednisone orally

Arm C: onvansertib + abiraterone and prednisone

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.

Group Type: EXPERIMENTAL

Onvansertib

Intervention Type: DRUG

Onvansertib orally

Abiraterone

Intervention Type: DRUG

Abiraterone orally

Prednisone

Intervention Type: DRUG

Prednisone orally

Interventions

Onvansertib

Onvansertib orally

Intervention Type: DRUG

Abiraterone

Abiraterone orally

Intervention Type: DRUG

Prednisone

Prednisone orally

Intervention Type: DRUG

Other Intervention Names

PCM-075

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Cardiff Oncology

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34646387 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1208-1579

Identifier Type: REGISTRY

Identifier Source: secondary_id

TROV-053

Identifier Type: -

Identifier Source: org_study_id