A Multi-Center Phase II Study Testing the Activity of Olaparib and AZD6738 (ATR Inhibitor) in Metastatic Castration-Resistant Prostate Cancer

University of Michigan Rogel Cancer Center3 个研究点分布在 1 个国家目标入组 49 人2019年10月31日

适应症Prostate Cancer

干预措施Olaparib AZD6738

概览

阶段: 2 期
干预措施: Olaparib
疾病 / 适应症: Prostate Cancer
发起方: University of Michigan Rogel Cancer Center
入组人数: 49
试验地点: 3
主要终点: Rate of Response (Complete Response [CR] or Partial Response [PR]) in DNA Repair Proficient (DRPro) Patients
状态: 进行中（未招募）
最后更新: 上个月

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

The purpose of this study is to test the effectiveness (how well the drugs work), safety, and tolerability of the investigational drug combination of olaparib and AZD6738 for all patients with metastatic castration-resistant prostate cancer.

注册库

clinicaltrials.gov

开始日期

2019年10月31日

结束日期

2028年8月1日

最后更新

上个月

研究类型

Interventional

研究设计

Single Group

性别

Male

研究者

发起方

University of Michigan Rogel Cancer Center

责任方

Sponsor

入排标准

入选标准

•Provision of informed consent prior to any study specific procedures
•Male ages 18 years and older at time of signing the informed consent form
•Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 within 42 days prior to registration
•Histologic or cytologic proof of prostate adenocarcinoma (excluding small-cell or neuroendocrine pathologies)
•Metastatic prostate cancer on CT, MRI or Bone scan
•Must have disease progression (while testosterone level is under 50 ng/dl) on prior therapy prior to study entry defined as one (or more) of the following:
•PSA progression defined as continuously rising PSA values measured a minimum of 1 week apart with a minimal starting value of 1.0 ng/mL
•Progression of bidimensionally measurable soft tissue or nodal metastasis by CT or MRI based on RECIST, v1.1
•Prior treatment with at least one of the following:
•One line of therapy in mCRPC

排除标准

•A diagnosis of ataxia telangiectasia
•Prior treatment with a PARP inhibitor (e.g. olaparib, veliparib, niraparib, rucaparib), AZD6738 or other DNA-damage response agents (e.g. cisplatin or carboplatin)
•Cytotoxic chemotherapy, first- or second-generation antiandrogen or CYP17 inhibitors are not permitted within 21 days or 5 half-lives of registration (whichever is longest) of planned treatment start. For clarity, enzalutamide requires 5 weeks washout.
•Major surgery \< 2 weeks prior to enrolment; patients must have recovered from any effects of major surgery
•Persistent toxicities (≥CTCAE Grade 2) caused by previous cancer therapy, besides Grade 2 alopecia and Grade 2 neuropathy (these are allowed).
•Patients with current or prior MDS/AML or with features suggestive of MDS/AML
•Any other malignancy which has been active or treated within the past 3 years, with the exception of non-melanomatous skin cancer, or Ta bladder cancer
•Patients with active brain metastases are excluded because of unknown penetration into the CNS. A confirmatory scan for asymptomatic patients is not required. Patients with a history of treated central nervous system (CNS) metastases are eligible provided they meet all of the following criteria: disease outside the CNS is present, no clinical evidence of progression since completion of CNS-directed therapy, minimum 3 weeks between completion of radiotherapy and registration and recovery from significant (Grade ≥ 3) acute toxicity with no ongoing requirement for \>10 mg of prednisone per day or an equivalent dose of other corticosteroid. If a patient must remain on steroids, they must have started the steady dose at least 28 days prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days prior to study treatment.
•Any of the following cardiac disease currently or within the last 6 months:
•Unstable angina pectoris

研究组 & 干预措施

Cohort 1 (DRPro)

Patients with metastatic castration-resistant prostate cancer (mCRPC) who are DNA repair proficient (DRPro).

干预措施: Olaparib

Cohort 1 (DRPro)

Patients with metastatic castration-resistant prostate cancer (mCRPC) who are DNA repair proficient (DRPro).

干预措施: AZD6738

Cohort 2 (DRDef)

Patients with metastatic castration-resistant prostate cancer (mCRPC) who are DNA repair deficient (DRDef).

干预措施: Olaparib

Cohort 2 (DRDef)

Patients with metastatic castration-resistant prostate cancer (mCRPC) who are DNA repair deficient (DRDef).

干预措施: AZD6738

结局指标

主要结局

Rate of Response (Complete Response [CR] or Partial Response [PR]) in DNA Repair Proficient (DRPro) Patients

时间窗: Up to 30 days after study completion (an average of 1 year)

Evaluated per radiographic response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or by Prostate Specific Antigen (PSA) (≥50% decline).

次要结局

Radiographic Response Rate in DRPro Patients(Up to 30 days after study completion (an average of 1 year for study completion))
Rate of Response (Complete Response [CR] or Partial Response [PR]) in DNA Repair Deficient (DRDef) Patients(Up to 30 days after study completion (an average of 1 year for study completion))
Progression-free Survival (PFS) in DRDef Patients(Up to 30 days after study completion (an average of 1 year for study completion))
Radiographic Response Rate in DRDef Patients(Up to 30 days after study completion (an average of 1 year for study completion))
PSA Progression-free Survival in DRDef Patients(Up to 30 days after study completion (an average of 1 year for study completion))
Duration of Combined Radiographic and PSA Response in DRPro Patients(Up to 30 days after study completion (an average of 1 year for study completion))
Progression-free Survival (PFS) in DRPro Patients(Up to 30 days after study completion (an average of 1 year for study completion))
PSA Progression-free Survival in DRPro Patients(Up to 30 days after study completion (an average of 1 year for study completion))
PSA Response Rate in DRPro Patients(Up to 30 days after study completion (an average of 1 year for study completion))
PSA Response Rate in DRDef Patients(Up to 30 days after study completion (an average of 1 year for study completion))
Duration of Combined Radiographic and PSA Response in DRDef Patients(Up to 30 days after study completion (an average of 1 year for study completion))
Adverse Events(Up to 30 days after study completion (an average of 1 year for study completion))
Incidence of Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML) and New Primary Malignancy(Up to 5 years after study completion (an average of 1 year for study completion))