Clinical Trials List
Protocol NumberD081DC00007
NCT Number(ClinicalTrials.gov Identfier)NCT02987543
2017-01-01 - 2021-12-31
Phase III
Recruiting5
Terminated4
ICD-10C61
Malignant neoplasm of prostate
ICD-9185
Malignant neoplasm of prostate
A Phase III, Open Label, Randomized Study to Assess the Efficacy and Safety of Olaparib (Lynparza) Versus Enzalutamide or Abiraterone Acetate in Men with Metastatic Castration-Resistant Prostate Cancer Who Have Failed Prior Treatment with a New Hormonal Agent and Have Homologous Recombination Repair Gene Mutations
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Trial Applicant
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Sponsor
AstraZeneca Taiwan Co., Ltd.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- - - 無
- 陳育青 無
- Yu-Chieh Tsai 無
- Ying-Chun Shen 無
- Yeong-Shiau Pu 無
- CHING-CHU LU 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- Tzu-chun Wei 無
- Tzu-Ping Lin 無
- Yen-Hwa Chang Division of Urology
- 朱力行 無
- 沈書慧 無
- Yi-Hsiu Huang 無
- 潘競成 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Cheng-Kuang Yang 無
- 熊小澐 無
- 洪啟峰 無
- Jian-Ri Li 無
- Chuan-Shu Chen 無
- Chia-Yen Lin 無
- Cheng-Che Chen 無
- 裘坤元 無
- 蔡世傳 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Rita cheng 無
- 張英勛 無
- 劉忠一 無
- Yung-Chang Lin 無
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Metastatic Castration-Resistant Prostate Cancer
Objectives
To investigate the effectiveness of olaparib in the treatment of prostate cancer with damaged DNA repair defects [homologous recombination repair (HRR) gene mutations], the results of comparison with enzalutamide or abiraterone, and the possible side effects.
Test Drug
Olaparib
Active Ingredient
Olaparib
Dosage Form
Tablet
Dosage
100
150
150
Endpoints
For mCRPC patients with BRCA1, BRCA2, or ATM mutations (population A), to evaluate the efficacy of olaparib compared to enzalutamide or abiraterone acetate selected by the trial host (use rPFS evaluation)
Inclution Criteria
1. *Provision of informed consent prior to any study-specific procedures.
2. *Male ≥ 18 years of age.
3. *Histologically confirmed diagnosis of prostate cancer.
4. *Candidate for treatment with enzalutamide or abiraterone acetate with documented current evidence of metastatic castration-resistant prostate cancer, where metastatic status is defined as at least one (1) documented metastatic lesion
on either bone scan or CT/MRI scan. Subjects whose disease spread is limited to regional pelvic lymph nodes or local recurrence (e.g. bladder, rectum) are not eligible.
5. Subjects must have progressed on prior NHA (e.g. abiraterone acetate and/or enzalutamide) for the treatment of mCRPC. Determination of progression is done per local investigator.
6. Serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within (≤) 28 days before randomization.
7. *Subjects without prior surgical castration must be currently taking and willing to continue luteinizing hormone-releasing hormone (LHRH) analog (agonist or antagonist) therapy throughout the duration of study treatment.
8. Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy). Determination of progression is done per local investigator.
9. Qualifying HRR mutation in tumor tissue by the Lynparza HRR Assay.
a. Either archival or de novo biopsies are acceptable.
b. If subjects have a mutation in one of the 15 HRR genes based on prior prostate cancer tissue specimen testing by the commercially available FoundationOne ® assay, they must have the mutation confirmed as a qualifying mutation by FMI. Residual DNA (stored at FMI) from the original FoundationOne test will be used for confirmation. Subjects who do not have sufficient residual DNA from their original test will be analysed in-silico for qualifying HRR gene mutations based on their original
FoundationOne test data, but these subjects must supply sufficient formalin fixed, paraffin embedded (FFPE) tumor sample to carry out retrospective central confirmation using the Lynparza HRR Assay.
10. Subjects must have normal organ and bone marrow function measured within (≤) 28 days prior to administration of study treatment as defined below:
a. Hemoglobin ≥ 10.0 g/dL with no blood transfusions in the past 28 days
b. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
c. Platelet count ≥ 100 x 109/L
d. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
e. Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN
f. Subjects must have an estimated creatinine clearance using the Cockcroft- Gault equation for males of ≥ 51 mL/min:
11. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
12. Subjectss must have a life expectancy ≥ 16 weeks
13. Must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male subjects should also use a highly effective form of contraception ([see appendix F for acceptable methods]) if they are of childbearing potential
14. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations at the institution, and completing electronic PRO instruments.
2. *Male ≥ 18 years of age.
3. *Histologically confirmed diagnosis of prostate cancer.
4. *Candidate for treatment with enzalutamide or abiraterone acetate with documented current evidence of metastatic castration-resistant prostate cancer, where metastatic status is defined as at least one (1) documented metastatic lesion
on either bone scan or CT/MRI scan. Subjects whose disease spread is limited to regional pelvic lymph nodes or local recurrence (e.g. bladder, rectum) are not eligible.
5. Subjects must have progressed on prior NHA (e.g. abiraterone acetate and/or enzalutamide) for the treatment of mCRPC. Determination of progression is done per local investigator.
6. Serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within (≤) 28 days before randomization.
7. *Subjects without prior surgical castration must be currently taking and willing to continue luteinizing hormone-releasing hormone (LHRH) analog (agonist or antagonist) therapy throughout the duration of study treatment.
8. Radiographic progression at study entry while on androgen deprivation therapy (or after bilateral orchiectomy). Determination of progression is done per local investigator.
9. Qualifying HRR mutation in tumor tissue by the Lynparza HRR Assay.
a. Either archival or de novo biopsies are acceptable.
b. If subjects have a mutation in one of the 15 HRR genes based on prior prostate cancer tissue specimen testing by the commercially available FoundationOne ® assay, they must have the mutation confirmed as a qualifying mutation by FMI. Residual DNA (stored at FMI) from the original FoundationOne test will be used for confirmation. Subjects who do not have sufficient residual DNA from their original test will be analysed in-silico for qualifying HRR gene mutations based on their original
FoundationOne test data, but these subjects must supply sufficient formalin fixed, paraffin embedded (FFPE) tumor sample to carry out retrospective central confirmation using the Lynparza HRR Assay.
10. Subjects must have normal organ and bone marrow function measured within (≤) 28 days prior to administration of study treatment as defined below:
a. Hemoglobin ≥ 10.0 g/dL with no blood transfusions in the past 28 days
b. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
c. Platelet count ≥ 100 x 109/L
d. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
e. Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN
f. Subjects must have an estimated creatinine clearance using the Cockcroft- Gault equation for males of ≥ 51 mL/min:
11. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
12. Subjectss must have a life expectancy ≥ 16 weeks
13. Must use a condom during treatment and for 3 months after the last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male subjects should also use a highly effective form of contraception ([see appendix F for acceptable methods]) if they are of childbearing potential
14. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations at the institution, and completing electronic PRO instruments.
Exclusion Criteria
1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
2. Previous randomization in the present study
3. Participation in another clinical study with an investigational product during the last 30 days prior to randomization.
4. Any previous treatment with PARP inhibitor, including olaparib
5. Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy. For example, subjects who have received prior mitoxantrone or platinum-based chemotherapy are excluded.
-Prior estramustine is allowed
6. Other malignancy (including MDS and MGUS) within the last 5 years except:
adequately treated non-melanoma skin cancer or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years.
7. Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
8. Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
9. Subjects receiving any systemic anti-cancer therapy (except radiotherapy) within 3 weeks prior to study treatment.
-Agents to maintain castrate status are authorized as detailed in inclusion criterion #7. Agents such as 5-α reductase inhibitors (finasteride, dutasteride), estrogen compounds (including estramustine) and megesterol are considered as anti-cancer agent and prohibited within 3 weeks prior to
study treatment
-Bone-targeted therapy with denosumab or zoledronic acid is allowed. If subjects are being treated with these agents, they should be on a stable regimen when entering the study
10. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
11. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required
washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
12. Persistent toxicities ( > grade 2, per the Common Terminology Criteria for Adverse Event (CTCAE)) caused by previous cancer therapy, excluding alopecia or toxicities related to the use of LHRH agonist or antagonist
13. Subjects with known brain metastases. A scan to confirm the absence of brain metastases is not required.
14. Subjects with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
15. Subjects inevaluable for both bone and soft tissue progression as defined by meeting both of the following criteria:
(a) A bone scan referred to as a superscan showing an intense symmetric activity in the bones
(b) No soft tissue lesion (measurable or non-measurable) that can be assessed by RECIST
16. Major surgery within 2 weeks of starting study treatment and subjects must have recovered from any effects of any major surgery.
17. Subjects considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia,
recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
18. Subjects unable to swallow orally administered medication and subjects with gastrointestinal disorders likely to interfere with absorption of the study medication.
19. Immunocompromised subjects, e.g., subjects who are known to be serologically positive for human immunodeficiency virus (HIV).
20. Subjects with a known hypersensitivity to olaparib or any of the excipients of the product.
21. Subjects with known active hepatitis (i.e. Hepatitis B or C)
-Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible.
-Subjects positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
22. Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
23. Whole blood transfusions in the last 120 days prior to entry into the study (packed red blood cells and platelet transfusions are acceptable).
2. Previous randomization in the present study
3. Participation in another clinical study with an investigational product during the last 30 days prior to randomization.
4. Any previous treatment with PARP inhibitor, including olaparib
5. Subjects who have any previous treatment with DNA-damaging cytotoxic chemotherapy. For example, subjects who have received prior mitoxantrone or platinum-based chemotherapy are excluded.
-Prior estramustine is allowed
6. Other malignancy (including MDS and MGUS) within the last 5 years except:
adequately treated non-melanoma skin cancer or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years.
7. Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
8. Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
9. Subjects receiving any systemic anti-cancer therapy (except radiotherapy) within 3 weeks prior to study treatment.
-Agents to maintain castrate status are authorized as detailed in inclusion criterion #7. Agents such as 5-α reductase inhibitors (finasteride, dutasteride), estrogen compounds (including estramustine) and megesterol are considered as anti-cancer agent and prohibited within 3 weeks prior to
study treatment
-Bone-targeted therapy with denosumab or zoledronic acid is allowed. If subjects are being treated with these agents, they should be on a stable regimen when entering the study
10. Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
11. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort ) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required
washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
12. Persistent toxicities ( > grade 2, per the Common Terminology Criteria for Adverse Event (CTCAE)) caused by previous cancer therapy, excluding alopecia or toxicities related to the use of LHRH agonist or antagonist
13. Subjects with known brain metastases. A scan to confirm the absence of brain metastases is not required.
14. Subjects with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
15. Subjects inevaluable for both bone and soft tissue progression as defined by meeting both of the following criteria:
(a) A bone scan referred to as a superscan showing an intense symmetric activity in the bones
(b) No soft tissue lesion (measurable or non-measurable) that can be assessed by RECIST
16. Major surgery within 2 weeks of starting study treatment and subjects must have recovered from any effects of any major surgery.
17. Subjects considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia,
recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
18. Subjects unable to swallow orally administered medication and subjects with gastrointestinal disorders likely to interfere with absorption of the study medication.
19. Immunocompromised subjects, e.g., subjects who are known to be serologically positive for human immunodeficiency virus (HIV).
20. Subjects with a known hypersensitivity to olaparib or any of the excipients of the product.
21. Subjects with known active hepatitis (i.e. Hepatitis B or C)
-Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible.
-Subjects positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
22. Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
23. Whole blood transfusions in the last 120 days prior to entry into the study (packed red blood cells and platelet transfusions are acceptable).
The Estimated Number of Participants
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Taiwan
12 participants
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Global
5500 participants
