A Phase 2 Study of PCM-075 (Onvansertib) in Combination With Abiraterone and Prednisone in Adult Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 3
- 主要终点
- Percentage of Participants Achieving Disease Control at or Before 12 Weeks
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
- •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)
排除标准
- •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.
- •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.
研究组 & 干预措施
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.
干预措施: Abiraterone (Drug)
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.
干预措施: Onvansertib (Drug)
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.
干预措施: Abiraterone (Drug)
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.
干预措施: Prednisone (Drug)
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.
干预措施: Onvansertib (Drug)
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.
干预措施: Abiraterone (Drug)
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.
干预措施: Prednisone (Drug)
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.
干预措施: Onvansertib (Drug)
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.
干预措施: Prednisone (Drug)
结局指标
主要结局
Percentage of Participants Achieving Disease Control at or Before 12 Weeks
时间窗: Baseline up to Week 12
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.
次要结局
- Mean Percentage Change From Baseline in PSA at 12 Weeks(Baseline and Week 12)
- Mean Absolute Change From Baseline in PSA at 12 Weeks(Baseline and Week 12)
- Median Percentage Change From Baseline in PSA at 12 Weeks(Baseline and Week 12)
- Median Absolute Change From Baseline in PSA at 12 Weeks(Baseline and Week 12)
- Time to PSA Progression or Death(Up to approximately 100 weeks)
- Time to Radiographic Progression or Death(Up to approximately 110 weeks)
- Percentage of Participants Achieving Radiographic Responses at or Before 12 Weeks(Baseline up to Week 12)
- Percentage of Participants Who Are Adherent to Study Treatment (PP Analysis) Achieving Disease Control at or Before 12 Weeks(Baseline up to Week 12)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Up to approximately 27 months)
- Number of Participants With DLTs(Arms A and B: up to one 21-day cycle; Arm C: up to two 14-day cycles)