Clinical Trial - NCT03414034

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

Recruiting

Sponsor: Trovagene, Inc.

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03414034

Protocol Info

Short Description: Phase 2 of PCM-075 plus Abiraterone and Prednisone in Metastatic CRPC Cancer
Long Description: A Phase 2 Study of PCM-075 in Combination with Abiraterone and Prednisone in Subjects with Metastatic Castration-Resistant Prostate Cancer
MGH Status: Open
Sponsor: Trovagene, Inc.
Disease Program: GU

Next Steps


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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.
Condition Title Intervention Phase
Metastatic Castration-Resistant Prostate Cancer Onvansertib Abiraterone Prednisone Phase 2
Study Type Interventional
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

Primary Outcome Measures

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] [Designated as safety issue: ]


Secondary Outcome Measures

Percentage Change from Baseline in PSA at 12 Weeks [Time Frame: Baseline and Week 12] [Designated as safety issue: ]

Maximal Percentage Change from Baseline in PSA [Time Frame: Baseline up to 20 months] [Designated as safety issue: ]

Absolute Change from Baseline in PSA Response [Time Frame: Baseline up to 20 months] [Designated as safety issue: ]

Time to PSA Progression per PCWG3 criteria [Time Frame: Baseline up to 20 months] [Designated as safety issue: ]

Time to Radiographic Progression per PCWG3 criteria [Time Frame: Baseline up to 20 months] [Designated as safety issue: ]

Radiographic Response per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [Time Frame: Baseline up to 20 months] [Designated as safety issue: ]

Number of Participants With Dose Limiting Toxicity (DLT) [Time Frame: Up to 20 months] [Designated as safety issue: ]

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)] [Designated as safety issue: ]

Estimated Enrollment: 64
Study Start Date: June 2018
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: October 2020
Arms Assigned Interventions

Experimental:Onvansertib + abiraterone and prednisone

Onvansertib, 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).
Drug:Prednisone
Prednisone orally

Experimental:Onvansertib, abiraterone and prednisone

PCM-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.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: Male

Accepts Healthly 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03414034

Locations

  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215
    • Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Trovagene, Inc.

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03414034
Other Study ID Numbers: U1111-1208-1579
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Trovagene, Inc.:

PLK1

PLK Inhibitor

Onvansertib

Additional relevant MeSH terms:

Prostatic Neoplasms

Prednisone

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019