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Metastatic Castration-Resistant Prostate CancerPhase 2NCT03414034

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

A Phase 2 study testing Onvansertib, Abiraterone and Prednisone in people with Metastatic Castration-Resistant Prostate Cancer, run by Cardiff Oncology at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Onvansertib, Abiraterone and Prednisone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
3 sitesUnited States
Study dates
14 Aug 2018to 16 Oct 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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)

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

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

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.

Being tested
Onvansertib, Abiraterone, Prednisone
Keywords
PLK1, PLK Inhibitor, Onvansertib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OnvansertibDrug

    Also called PCM-075

    Onvansertib orally

  • AbirateroneDrug

    Abiraterone orally

  • PrednisoneDrug

    Prednisone orally

Study groups in NCT03414034
Study groupRoleWhat they receive
Arm A: onvansertib + abiraterone and prednisoneExperimentalOn 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.
Receives: Drug: Onvansertib; Drug: Abiraterone; Drug: Prednisone
Arm B: onvansertib + abiraterone and prednisoneExperimentalOn 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.
Receives: Drug: Onvansertib; Drug: Abiraterone; Drug: Prednisone
Arm C: onvansertib + abiraterone and prednisoneExperimentalOn 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.
Receives: Drug: Onvansertib; Drug: Abiraterone; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Achieving Disease Control at or Before 12 Weeks

    Disease control was defined as lack of prostate-specific antigen (PSA) progression per Prostate Cancer Working Group 3 (PCWG3) criteria: not having an increase in PSA from Baseline or nadir ≥ 25% and ≥ 2 ng/mL during the first 12 weeks of PSA assessments. Participants that do not have 12 weeks of PSA assessments were considered not to have demonstrated PSA progression control in this analysis. If a participant achieved disease control prior to Week 12, but relapsed at, or before Week 12, disease control was still considered achieved. The 90% confidence intervals were calculated using Wilson Confidence Interval.

    Measured: Baseline up to Week 12

Secondary outcomes (10)

  1. Mean Percentage Change From Baseline in PSA at 12 Weeks

    PSA level was measured via blood sample. Mean and standard deviation change is reported.

    Measured: Baseline and Week 12

  2. Mean Absolute Change From Baseline in PSA at 12 Weeks

    PSA level was measured via blood sample. Mean and standard deviation change is reported.

    Measured: Baseline and Week 12

  3. Median Percentage Change From Baseline in PSA at 12 Weeks

    PSA level was measured via blood sample. Median, minimum and maximum change is reported.

    Measured: Baseline and Week 12

  4. Median Absolute Change From Baseline in PSA at 12 Weeks

    PSA level was measured via blood sample. Median, minimum and maximum change is reported.

    Measured: Baseline and Week 12

  5. Time to PSA Progression or Death

    Time to PSA progression in weeks is defined as time from Cycle 1 Day 1 (initiation of treatment) until initiation of any PSA progression per PCWG3 criteria: an increase in PSA from Baseline or nadir ≥ 25% and ≥ 2 ng/mL. If a participant discontinued from the study without confirmed PSA progression or death, then they were censored at the last PSA laboratory date. Kaplan-Meier method was used.

    Measured: Up to approximately 100 weeks

  6. Time to Radiographic Progression or Death

    Time to radiographic progression in weeks is defined as time from Cycle 1 Day 1 (initiation of treatment) until initiation of any radiographic progression per PCWG3 criteria. If a participant discontinued from the study without confirmed radiographic progression or death, then they were censored at the last valid assessment date.

    Measured: Up to approximately 110 weeks

  7. Percentage of Participants Achieving Radiographic Responses at or Before 12 Weeks

    Radiographic response is defined as the best overall response between Cycle 1 Day 1 and 12 weeks post-baseline being stable disease (SD) or better (partial response [PR] or complete response [CR]) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1):

    CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm. All lymph nodes must have been non-pathological in size (< 10mm short axis).

    PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.

    SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).

    PD: at least a 20% increase in the sum of diameters of target lesions. The sum must also demonstrate an increase of at least 5mm. Unequivocal progression of existing non-target lesions.

    Measured: Baseline up to Week 12

  8. Percentage of Participants Who Are Adherent to Study Treatment (PP Analysis) Achieving Disease Control at or Before 12 Weeks

    Disease control was defined as lack of PSA progression per PCWG3 criteria: not having an increase in PSA from Baseline or nadir ≥ 25% and ≥ 2 ng/mL during the first 12 weeks of PSA assessments. Participants that do not have 12 weeks of PSA assessments were considered not to have demonstrated PSA progression control in this analysis. If a participant achieved disease control prior to Week 12, but relapsed at, or before Week 12, disease control was still considered achieved. The 90% confidence intervals were calculated using Wilson Confidence Interval.

    Measured: Baseline up to Week 12

  9. Number of Participants With Treatment Emergent Adverse Events (TEAEs)

    Adverse events (AEs) are defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs are defined as AEs with a start date after Cycle 1 Day 1. AE severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 on a scale from Grade 1 (mild) to Grade 5 (death related to AE).

    Measured: Up to approximately 27 months

  10. Number of Participants With DLTs

    DLTs are defined as a CTCAE Grade 4 hematologic AE or CTCAE Grade ≥ 3 non-hematologic AE that is considered related to the study drug.

    Measured: Arms A and B: up to one 21-day cycle; Arm C: up to two 14-day cycles

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jan 2018
  2. Study start14 Aug 2018
  3. Primary completion16 Oct 2023
  4. Study completion16 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03414034
Sponsor's protocol ID
TROV-053
Other IDs
U1111-1208-1579
Status last verified
Oct 2024
First submitted
22 Jan 2018
Last updated
7 Nov 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 34646387

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Onvansertib, Abiraterone and Prednisone in people with Metastatic Castration-Resistant Prostate Cancer, run by Cardiff Oncology at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Achieving Disease Control at or Before 12 Weeks (time frame: Baseline up to Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03414034, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2024.

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