Metastatic castration-resistant prostate cancer
Conditions
Interventions
Study drug:Olaparil tablets 300mg orally twice daily
Sponsors
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Informed consent has been provided prior to the commencement of any study procedure; 2. Male and >=18 years of age; 3. ECOG's physical status is 0-2; 4. Histologically confirmed adenocarcinoma of the prostate; 5. Subjects must have previously received NHA (e.g. Abiraterone acetate and/or enzyluamine) for mHSPC or nmCRPC and develop disease progression to mCRPC. Disease progression was determined by local investigators based on the diagnostic criteria for mCRPC (DIAGNOSTIC criteria for CRPC: testosterone maintained at castrated levels (testosterone levels below 50 ng/dL or 1.7 nmol/L) and at least one of the following criteria: (1) Biochemical progress: PSA was increased for three consecutive times, and the interval between the two tests was at least one week, which was more than 50% higher than the lowest value, and PSA was > 2 ng/mL; (2) Imaging progression: New lesions: Bone scan reveals two or more new bone lesions or one soft tissue lesion that meets the RECIST criteria. Symptom progression alone is not enough to diagnose CRPC. Radiographic evidence of metastatic lesions was confirmed based on CRPC to confirm mCRPC); 6. The serum testosterone level of subjects before enrollment was =10mm as measured by CT or MRI at baseline, or a shorter diameter of >=15mm if the lesion is lymph node, and the lesion is suitable for repeated measurement); 9. Subjects must undergo NGS testing to confirm the presence of at least one HRR gene mutation in tumor tissue and/or plasma CT-DNA: (1) Archived or freshly punctured biopsies are acceptable; (2) Qualified HRR gene mutations are BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD 51C, RAD51D and RAD54L mutations confirmed by the laboratory of the research Center; 10. Subjects' baseline organ and bone marrow function measurements must be normal, as defined below: (1) Hemoglobin >= 10.0g /dL in the absence of prior transfusion within 28 days; (2) Neutrophil absolute count >=1.5*10^9/L; (3) Platelet count >=100*10^9/L; (4) Total bilirubin =51 mL/min (estimated creatinine clearance =[140- age (years)]× body weight (kg)/serum creatinine (mg/dL) / 72); 11. Male subjects were surgically sterilized or used an acceptable method of contraception (defined as barrier contraception containing spermicide) to prevent their partner from becoming pregnant during the duration of the study and for 12 weeks after the last olaparil administration; 12. The expected survival of the subject must be >=12 weeks; 13. During the duration of the study, the subjects were willing and able to comply with the protocol, including receiving treatment, planning visits, and hospital visits.
Exclusion criteria
Exclusion criteria: 1. Participate in the design and/or implementation of the study (applicable to researchers and/or center staff); 2. Previous studies have been included in this study; 3. Participated in another drug clinical study or planned to participate in other interventional clinical study within 30 days prior to enrollment; 4. Prior treatment with any PARP inhibitor, including olaparil; 5. Prior chemotherapy with any DNA-damaging cytotoxic drug, except for non-prostate cancer, and last administration at least 5 years prior to enrollment in this study. For example, patients who had previously received mitoxantrone or platinum-containing chemotherapy for prostate cancer were excluded; 6. Other malignant tumors in the past 5 years. 7. Resting ecg shows uncontrolled or underlying cardiac conditions (e.g., but not limited to: unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, prolonged QT interval > 500 ms with Fridericia correction, congenital long QT syndrome); 8. Subjects received any systemic anticancer therapy (except radiotherapy) within 3 weeks prior to study treatment. (1) Drugs used to maintain the castration state are permitted as described in inclusion criteria #7. 5-a reductase inhibitors (finasteride, dutaride), estrogen compounds, and megestrol are anticancer agents and are prohibited for 3 weeks prior to study treatment; (2) Allows the treatment of bone metastases with desomumab or bisphosphonates such as zoledronic acid; 9. The combination of a known potent CYP3A inhibitor (e.g., itraconazole, telithromycin, clarithromycin, ritonavir or cobitate-enhanced protease inhibitor, indenavir, saquinavir, nefinavir, popavir, tiralavir) or a moderate CYP3A inhibitor (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil), A 2 week washout period is required before Olapalil treatment begins; 10. Combination of strong CYP3A inducers (e.g., phenobarbital, entzaluramide, phenytoin, rifampicin, rifambutin, rifapentin, carbamazepine, nevirapine, and Hypericum perforatum) or medium CYP3A inducers (e.g., bosentan, efavirenz, modafinil). When combined with phenobarbital, a 5-week washout period is required before the start of olaparil treatment and a 3-week washout period is required when combined with other agents; 11. Long-term toxicity (CTCAE > level 2) due to previous cancer treatment, excluding hair loss or toxicity due to use of LHRH agonists or antagonists; 12. Subjects known to have BMS (scan confirmation of absence of BMS is not required); 13. Subjects with myelodysplastic syndrome/acute myeloid leukemia or characteristics suggestive of MDS/AML; 14. Subjects who are unable to swallow oral medications and/or have gastrointestinal disorders that may interfere with absorption of study medications; 15. Subjects known to be allergic to olaparil or any excipients of this product; 16. Immunocompromised subjects, such as those who test serologically positive for human immunodeficiency virus (HIV); 17. Subjects known to have active hepatitis, such as hepatitis B or C; 18. The subject has a serious, uncontrollable medical disease or non-malignant systemic disease, or an uncontrollable active infection. (E.g., but not limited to uncontrolled ventricular arrhythmias, myocardial infarction within 12 weeks, uncontrollable seizures, extensive interstitial lung disease in both lungs, or mental illness that prevents the signing of informed consent.)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comprehensive response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Time of no progression on imaging;Disease control rate (DCR);Adverse events;Time to PSA progression (TTPP); | — |
Countries
China
Contacts
Public ContactJian Huang
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Outcome results
None listed