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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03414034
Recruitment Status : Recruiting
First Posted : January 29, 2018
Last Update Posted : January 8, 2019
Information provided by (Responsible Party):
Trovagene, Inc.

Brief Summary:
The purpose of the phase 2 study is to determine whether Onvansertib given orally once daily for 5 consecutive days every 21 days is safe and tolerable in adult patients 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.

Condition or disease Intervention/treatment Phase
Metastatic Castration-Resistant Prostate Cancer Drug: Onvansertib Drug: Abiraterone Drug: Prednisone Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 18, 2018
Estimated Primary Completion Date : May 14, 2019
Estimated Study Completion Date : June 11, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Prednisone

Arm Intervention/treatment
Experimental: Onvansertib + abiraterone and prednisone
Onvansertib, 24 mg/m2, administered orally Day 1 through Day 5 every 21 days (1 cycle) in combination with the standard dose of abiraterone (1000 mg orally once daily; four 250 mg tablets or two 500 mg film-coated tablets) and prednisone (5 mg orally once daily).
Drug: Onvansertib
Onvansertib orally

Drug: Abiraterone
Abiraterone orally

Drug: Prednisone
Prednisone orally

Primary Outcome Measures :
  1. Percentage of Participants With Lack of Prostate-specific Antigen (PSA) Progression per Prostate Cancer Working Group 3 (PCWG3) criteria After 12 Weeks [ Time Frame: Week 12 ]

Secondary Outcome Measures :
  1. Percentage Change from Baseline in PSA at 12 Weeks [ Time Frame: Baseline and Week 12 ]
  2. Maximal Percentage Change from Baseline in PSA [ Time Frame: Baseline up to 20 months ]
  3. Absolute Change from Baseline in PSA Response [ Time Frame: Baseline up to 20 months ]
  4. Time to PSA Progression per PCWG3 criteria [ Time Frame: Baseline up to 20 months ]
  5. Time to Radiographic Progression per PCWG3 criteria [ Time Frame: Baseline up to 20 months ]
  6. Radiographic Response per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: Baseline up to 20 months ]
  7. Number of Participants With Dose Limiting Toxicity (DLT) [ Time Frame: Up to 20 months ]
    DLT is defined as a grade 4 hematologic adverse event (AE) or nonhematologic AE of Grade ≥3 considered related to the study drug(s).

  8. Number of Participants With Adverse Events per Common Terminology Criteria for Adverse Events (CTCAE) [ Time Frame: Baseline up to 30 days after last dose of study drug (Up to 20 months) ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No

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. Patients 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. Subject currently receiving abiraterone and prednisone for CRPC.
  7. Subject has been on abiraterone for castration-sensitive prostate cancer (CSPC) or castration-resistant prostate cancer (CRPC). Subjects 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.

    Subjects 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 0.5 ng/mL and one confirmatory value not showing a decline, while on abiraterone therapy.
  9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  10. Subject has adequate bone marrow and organ function as shown by:

    • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
    • Platelets ≥ 100 x 109/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 subjects 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03414034

Contact: Central Contact Lead 858-952-7652

United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact    617-724-4000      
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact    617-632-9281      
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact    617-632-6328      
Sponsors and Collaborators
Trovagene, Inc.

Responsible Party: Trovagene, Inc. Identifier: NCT03414034     History of Changes
Other Study ID Numbers: TROV-053
U1111-1208-1579 ( Registry Identifier: WHO )
First Posted: January 29, 2018    Key Record Dates
Last Update Posted: January 8, 2019
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Trovagene, Inc.:
PLK Inhibitor

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents