Clinical Trials /

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

NCT03414034

Description:

The purpose of the phase 2 study is to determine whether Onvansertib given orally once daily for 5 consecutive days every 14 or 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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: TROV-053
  • SECONDARY ID: U1111-1208-1579
  • NCT ID: NCT03414034

Conditions

  • Metastatic Castration-Resistant Prostate Cancer

Interventions

DrugSynonymsArms
OnvansertibPCM-075Onvansertib + abiraterone and prednisone
AbirateroneOnvansertib + abiraterone and prednisone
PrednisoneOnvansertib + abiraterone and prednisone

Purpose

The purpose of the phase 2 study is to determine whether Onvansertib given orally once daily for 5 consecutive days every 14 or 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.

Trial Arms

NameTypeDescriptionInterventions
Onvansertib + abiraterone and prednisoneExperimentalOnvansertib, 24 mg/m^2, 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).
  • Onvansertib
  • Abiraterone
  • Prednisone
Onvansertib, abiraterone and prednisoneExperimentalPCM-075 administered orally once daily at a dose of 24 mg/m^2 for five days (Day 1 through Day 5) out of a 14-day cycle. Beginning on Day 1 and continuing uninteruupted throughout each cycle, patients will also receive abiraterone and prednisone. Dosing of PCM-075 can be administered at the same time the patient is administered their dose of abiraterone.
  • Onvansertib
  • Abiraterone
  • Prednisone

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. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Trovagene, Inc.

Trial Keywords

  • PLK1
  • PLK Inhibitor
  • Onvansertib

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