纳入标准病理活检证实为前列腺腺癌2例。至少符合下列条件之一: •常规或PET成像cN1 •5年级组 •4级组，PSA≥10 ng/mL •3级组，PSA≥20 ng/mL •MRI上影像学表现为T3的可能性高，分级组≥2 •分级组3,PSA≥10 ng/mL，活检核≥50%阳性年龄≥18岁Ecog < 1 5。按照规定，有足够的器官和骨髓功能。6.在治疗期间及治疗后至少90天内使用有效避孕措施(如避孕套)。男性还必须同意在参与研究期间以及之后至少90天内不捐献精子。7.国际前列腺症状评分(IPSS)≤20身体状况适合治疗，并同意随访。 Ability to understand and the willingness to sign a written informed consent 10. Tissue available for MiOncoSeq testing to assign DNA repair deficiency status Exclusion Criteria 1. Clinical or radiographic evidence of distant metastatic disease by CT/bone scan 2. Clinical or radiographic evidence of high probability of clinical T4 disease 3. Prostate gland size >80 cc measured by ultrasound or MRI 4. Prominent median lobe assessed by treating physician 5. Lack of tissue from biopsy to be sent for correlative studies 6. Any prior treatment for prostate cancer (incudes TURP, chemotherapy, radiation therapy, or anti-androgen therapy) 7. Prohibited within 30 days prior to administration to study treatment: spironolactone and other investigational drug therapies. 8. Prohibited 3 months before participant registration and during administration of study treatment: non-steroidal anti-androgens (e.g., bicalutamide, flutamide, nilutamide), steroidal antiandrogens (megestrol acetate, cyproterone acetate), oral ketoconazole, chemotherapy, immunotherapy, estrogens, radiopharmaceuticals. 9. History of prior pelvic radiation therapy 10. Concurrent treatment with strong CYP3A4 inducers such as phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital 11. Enrollment concurrently in another investigational drug study within 1 month of registration 12. History of another active malignancy within the previous 3 years except for adequately treated skin cancer or superficial bladder cancer 13. History of or active Crohn's disease or ulcerative colitis 14. Contraindication to or inability to tolerate MRIs 15. Patients with severe depression 16. Uncontrolled diabetes or known HbA1c>10 17. Any gastrointestinal disorder affecting absorption 18. Active pituitary or adrenal dysfunction 19. Patients with significant cardiovascular disease potentially including severe / unstable angina, recent history of myocardial infarction, clinically significant heart failure, cerebrovascular disease, venous thromboembolic events, clinically significant arrhythmias) 20. Uncontrolled hypertension with persistently elevated systolic blood pressure >160 mmgHg or diastolic blood pressure >100 mmHg despite anti-hypertensive agents. 21. Prolonged QTc >450 ms or any ECG changes that interfere with QT interval interpretation 22. Major surgery within 1 month of registration 23. History of myelodysplastic syndrome or leukemia 24. A known hypersensitivity to niraparib, abiraterone acetate, leuprolide, and/or prednisone 25. Active infection or other medical condition that would be a contraindication to prednisone use 26. Patients with known active hepatitis or chronic liver disease including cirrhosis 27. Any condition that in the opinion of the investigator would preclude participation in this study
1.年龄≥18岁。2.适当的分期研究确定患者为AJCC第七版临床分期T1 (a, b，或c)或T2 (a, b，或c)前列腺腺癌。在适当的分期研究后，患者不应有区域或远处转移的直接证据。有关AJCC第7版登台标准的详细信息，请参见附录I。癌症的组织学确认需要在注册后12个月内进行活检。如果直肠指诊延期，可仅通过多参数影像学评估t分期。3.患者的Zubrod表现状态必须为0-2(定义见附录II)。 4. The Gleason summary score should be less than or equal to 7 [Grade group 1 (Gleason 3+3=6), group 2 (Gleason 3+4=7), and group 3 (Gleason 4+3=7) are allowed]. See Appendix III for details on definitions. While a template biopsy is recommended, it is not required in the case of MRI fusion biopsy performed on all dominant MR lesions (defined as PIRADS v2 4-5). 5. Baseline AUA symptom score ≤19 (see Appendix IV for questionnaire) without need for maximum medical therapy (specifically, not on tamsulosin 0.8mg daily). 6. EPIC sexual domain composite score 60-100 (see Appendix V). 7. Multi-parametric MRI evaluation of the prostate is required for this study within 12 months of registration. Gross radiographic disease on MRI (defined as PIRADS v2 score 3-5) must be > 5mm at minimum distance from at least one side's neurovascular bundle, which is typically the closest of the neurovascular elements to the prostate. 8. The serum PSA should be less than or equal to 20 ng/ml within 90 days of registration. -Study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of ADT or anti-androgen therapy; (3) within 30 days after discontinuation of finasteride; (4) within 90 days after discontinuation of dutasteride; (5) within 5 days of a digital rectal examination (which is not a required exam on the protocol). 9. Ultrasound or MRI based volume estimation of prostate gland ≤ 80 grams. Cytoreduction therapy (finasteride or dutasteride only) may be considered for those with >60 gram size. 10. All patients must be willing and capable to provide informed consent to participate in the protocol within the 30 days prior to registration.
排除标准:
1.临床(指直肠检查)显示前列腺外延伸(T3a)或精囊受累(T3b)的受试者。MRI证据不明确/潜在但不确定的前列腺外伸展是允许的，只要它是单侧的，而不是在腺的一侧，建议保留神经血管元件。在MRI显示可能的囊外延伸的模棱两可的病例中，酌情决定权留给治疗的医生。2.总体疾病(定义为PIRADS v2评分为3-5个病变)的MRI证据≤5mm的两个神经血管束，这是本方案中计划保留的最接近的神经血管束元素。3.所有三个中间危险因素(PSA >10和≤20,Gleason 7，临床分期T2b-T2c)均阳性且模板活检核数≥50%的患者不符合条件。4.不能进行多参数MRI检查。 5. Evidence of metastatic disease. Note bone scan is not required for this study given the low-intermediate NCCN risk cohort to be enrolled. 6. Evidence of clinical nodal involvement of the pelvis. Biopsy is required for lymph nodes over ≥1.5cm in short-axis measured size. 7. No currently active ADT or anti-androgen therapy at time of registration is allowed. Further, no more than 3 cumulative months of prior ADT or anti-androgen therapy is allowed. If either has been used by the patient, there must be a demonstration of testosterone recovery (>50ng/dL serum blood level), EPIC sexual domain score ≥60, and at least 1 month between demonstration of testosterone recovery and study registration (any one measurement of testosterone recovery suffices). 8. Testosterone ≤ 50 ng/dL (any one measurement >50 ng/dL suffices for inclusion) within 90 days of study entry. 9. Subjects who have had previous pelvic radiotherapy or have had chemotherapy or surgery for prostate cancer. 10. Subjects who have plans to receive other concomitant or post treatment adjuvant antineoplastic therapy while on this protocol including surgery, cryotherapy, conventionally fractionated radiotherapy, hormonal therapy, or chemotherapy given as part of the treatment of prostate cancer. 11. Subjects who have undergone previous transurethral resection of the prostate (TURP) within 1 year of enrollment or ablative procedures to the prostate for benign prostatic hyperplasia or other conditions (i.e. cryotherapy, HIFU). 12. Subjects who have baseline severe urinary symptoms, as defined by AUA symptom score >19 (alpha-blocker medication allowed except if taking tamsulosin 0.8mg daily at baseline which indicates compensated severe symptoms and also can affect sexual function). 13. Subjects who have a history of significant psychiatric illness that would confound informed consent. 14. Severe, active co-morbidity, defined as follows: 1. Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months 2. Myocardial infarction within the last 6 months 3. Acute bacterial or fungal infection requiring intravenous antibiotics at time of registration 4. Patients with active inflammatory colitis (including Crohn's Disease and ulcerative colitis) currently requiring systemic steroids and/or systemic immunosuppression are not eligible. 15. Subjects with a known allergy to polyethylene glycol hydrogel (rectal spacer material) or contraindication to spacer products (SpaceOAR). 16. Subjects with uncontrolled coagulation disorder which cannot be controlled with anticoagulants. 17. Men active with partners of reproductive potential who do not agree that they will use an effective contraceptive method during treatment and 6 months after treatment. 18. Men who require erectile function medication or aid to achieve an erection sufficient for intercourse. Ability to achieve erection sufficient for intercourse without medication or aid at least once time in the month prior to registration is sufficient for inclusion. 19. Men who have clinically significant penile malformation (i.e. Peyronie's disease) or history of penile implantation are excluded. 20. If DRE is performed, patient may not have palpable disease on side of gland to be planned for neurovascular sparing. Given the poor accuracy of DRE, such a finding should be confirmed by MRI and/or biopsy to harbor actual disease before excluding a patient on this basis.
符合本研究纳入条件的患者必须满足以下所有标准:自愿提供知情同意。2.男女患者年龄≥18岁(或根据当地法律法规已达到成年年龄，如果年龄为> 18岁)。3.晚期实体瘤患者，之前至少有一种系统治疗失败，或标准治疗不存在，且符合以下条件，可进入本研究的相应部分:患者必须在组织学或细胞学上确诊为晚期复发性或转移性实体瘤。2.根据RECIST 1.1至少有一个可测量的病变。(卵巢癌参与者必须根据RECIST 1.1标准有可测量的疾病，或根据CA125 GCIG标准有可评估的癌症; Prostate cancer participants must have measurable disease by RECIST 1.1 criteria or evaluable cancer via PSA response). 3. Population eligibility: •符合第1部分剂量增加条件的患者:具有任何DDR基因1)或PIK3CA 2)突变的晚期实体瘤，且已失败或不能耐受标准治疗或目前没有标准治疗。 •符合第2部分剂量扩大条件的患者: •队列1:伴有DDR3基因突变的晚期实体瘤 •队列2:PIK3CA热点突变的晚期实体瘤 •队列3:获得性PARP抑制剂耐药的晚期高级别浆液性卵巢癌、输卵管癌或原发性腹膜癌患者4) •队列4:伴有DDR3基因突变并获得性PARP抑制剂耐药的晚期实体瘤4)。 •队列5:耐铂/难治性复发高级别浆液性卵巢癌、输卵管癌或原发性腹膜癌。4.肿瘤组织样本(新鲜肿瘤活检或档案肿瘤组织样本)或血液样本的可用性。5.东部肿瘤合作集团(ECOG)绩效状态≤1。关键
排除标准:
符合本研究条件的患者必须不符合以下任何一个标准:患者在接受第一剂研究治疗前28天内或5次半衰期(以较短者为准)内接受过任何抗癌治疗(包括化疗、靶向治疗、激素治疗、生物治疗、免疫治疗或其他研究药物)，或未从此类治疗副作用中恢复的患者。2.有奥拉帕尼治疗禁忌症或以前不耐受奥拉帕尼的患者。3.既往接受过PARP抑制剂、PI3Kα抑制剂、AKT抑制剂或mTOR抑制剂治疗的患者(第2部分剂量扩展队列1和2)。4.在第一剂试验产品前4周内接受根治性放疗(包括超过25%的骨髓放疗)或在2周内接受骨转移的局部姑息性放疗。5.在研究治疗开始前，既往治疗未恢复到基线或≤CTCAE 1级的任何毒性反应(脱发除外)。 6. Patients with an established diagnosis of diabetes mellitus including steroid-induced diabetes mellitus. 7. Major surgery or had significant traumatic injury within 28 days prior to the first dose of the investigational product or has not recovered from major side effects.