Clinical Trials List
Protocol NumberD933IC00003
NCT Number(ClinicalTrials.gov Identfier)NCT03459846
Completed
2018-02-05 - 2022-12-31
Phase II
Terminated8
Study ended1
ICD-10C67
Malignant neoplasm of bladder
ICD-9233.9
Carcinoma in situ of other and unspecified urinary organs
A Phase II, Randomized, Multi-Center, Double-Blind, Comparative Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Olaparib for First-Line Treatment in Cisplatin-Ineligible Patients With Unresectable Stage IV Urothelial Cancer
-
Trial Applicant
-
Sponsor
AstraZeneca Taiwan Co., Ltd.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Shian-Shiang Wang 無
- 王樹吉 無
- Chuan-Shu Chen 無
- 洪晟鈞 Division of General Surgery
- Cheng-Che Chen 無
- Cheng-Kuang Yang 無
- 盧嘉文 無
- 裘坤元 無
- Chia-Yen Lin 無
- 熊小澐 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Wei-Pang Chung Division of Hematology & Oncology
- Yuh-Shyan Tsai Division of Urology
- Shang-Yin Wu Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
- Wu-Chou Su Division of Hematology & Oncology
- Jiann-Hui Ou Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- 陳彥仰 Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- Shau-Hsuan Li Division of Hematology & Oncology
- 吳佳哲 Division of Hematology & Oncology
- Tai-Jan Chiu Division of Hematology & Oncology
- Meng-Jer Hsieh Division of Hematology & Oncology
- 饒坤銘 Division of Hematology & Oncology
- 劉建廷 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Che-Hung Lin Division of Hematology & Oncology
- Chao-Hsiang Chang Division of Urology
- Ming-Hung Tsai Division of Hematology & Oncology
- Chi-Ping Huang Division of Urology
- Chi-Ching Chen Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
- Wei-Ching Lin Division of Radiology
- Chi-Rei Yang Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- CHUNG-HSIN CHEN Division of Urology
- JHE-CYUAN GUO Division of Hematology & Oncology
- Yeong-Shiau Pu Division of Urology
- YU-CHUAN LU Division of Urology
- Ying-Chun Shen Division of Hematology & Oncology
- - - Division of Urology
- 洪士鈞 Division of Urology
- - - Division of Urology
- Chia-Chi Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Hsiao-Jen Chung Division of Urology
- Chueh-Chuan Yen Division of Hematology & Oncology
- Mu-Hsin Chang Division of Hematology & Oncology
- 沈書慧 Division of Radiology
- Yen-Hwa Chang Division of Urology
- Tzu-Hao Huang Division of Urology
- 潘競成 Division of Others
- Tzeon-jye Chiou Division of Hematology & Oncology
- Tzu-Ping Lin Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Principal Investigator
Co-Principal Investigator
- Su-Peng Yeh 未分科
Audit
None
Co-Principal Investigator
- Kai-Jie Yu Division of Hematology & Oncology
- I-hung Shao Division of Hematology & Oncology
- 張英勛 Division of Hematology & Oncology
- Po-Jung Su Division of Hematology & Oncology
- Hong-Cheng Gan Division of Hematology & Oncology
- Rita cheng Division of Hematology & Oncology
- Yung-Chia Kao Division of Hematology & Oncology
- 劉忠一 Division of Hematology & Oncology
- Cheng-Lung Hsu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
3 Stop recruiting
Audit
None
Co-Principal Investigator
- Shu-Pin Huang Division of Urology
- Hsin-Chih Yeh Division of Urology
- Sheng-Chen Wen Division of Urology
- Ching-Chia Li Division of Urology
- Hsiang Ying Lee Division of Urology
- Hung-Lung Ke Division of Urology
- Yung-Chin Lee Division of Urology
- 黃俊農 Division of Urology
- Wei-Ming Li Division of Urology
- Tsung-Yi Huang Division of Urology
The Actual Total Number of Participants Enrolled
2 Study ended
Condition/Disease
urothelial cancer
Objectives
To evaluate the efficacy and safety of durvalumab combined with olaparib as the first-line therapy, compared with durvalumab combined with placebo (durvalumab monotherapy), in the treatment of patients with unresectable stage 4 urothelial cancer who are not suitable for platinum-containing drug therapy Sex
Test Drug
Durvalumab(MEDI4736)
Olaparib
Olaparib
Active Ingredient
Humanized anti-PD-L1 mAb
Olaparib
Olaparib
Dosage Form
Injection
Tablet
Tablet
Dosage
50
100
150
100
150
Endpoints
Primary objective:
PFS as determined by Investigator assessment according to RECIST 1.1
Secondary objectives:
OS
Additional secondary objectives:
DoR, ORR, and PFS6 according to RECIST 1.1 using Investigator assessment
OS18
PFS, DoR, ORR, and PFS6 according to RECIST 1.1 using Investigator assessment
Concentration of durvalumab and olaparib
Presence of ADAs for durvalumab
EORTC QLQ-C30: Global health status/QoL,
functioning (physical), and multi-term symptoms (fatigue and pain)
Safety objective
AEs/SAEs, physical examinations, laboratory findings (including clinical chemistry, hematology and urinalysis), WHO/ECOG performance status, and vital signs
Exploratory objectives
PGIC
EQ-5D-5L will be used to derive health state utility based on patient-reported data
Biomarkers (eg, DNA or ctDNA alterations, protein expression detected by IHC, change in ctDNA levels, and mRNA expression) correlating with clinical response
PFS as determined by Investigator assessment according to RECIST 1.1
Secondary objectives:
OS
Additional secondary objectives:
DoR, ORR, and PFS6 according to RECIST 1.1 using Investigator assessment
OS18
PFS, DoR, ORR, and PFS6 according to RECIST 1.1 using Investigator assessment
Concentration of durvalumab and olaparib
Presence of ADAs for durvalumab
EORTC QLQ-C30: Global health status/QoL,
functioning (physical), and multi-term symptoms (fatigue and pain)
Safety objective
AEs/SAEs, physical examinations, laboratory findings (including clinical chemistry, hematology and urinalysis), WHO/ECOG performance status, and vital signs
Exploratory objectives
PGIC
EQ-5D-5L will be used to derive health state utility based on patient-reported data
Biomarkers (eg, DNA or ctDNA alterations, protein expression detected by IHC, change in ctDNA levels, and mRNA expression) correlating with clinical response
Inclution Criteria
1. Capable of giving a signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, Health
Insurance Portability and Accountability Act in the US and EU Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
2. Provision of signed and dated, written ICF prior to any mandatory study-specific procedures, sampling, and analyses.
3. Provision of signed and dated, written genetic informed consent (optional) prior to collection of sample for genetic analysis.
The ICF process is described in Appendix A3.
4. 18 years or older, at the time of signing the ICF. For subjects aged <20 years and enrolled in Japan, a written ICF should be obtained from the subject and his or her legally acceptable representative.
Type of patient and disease characteristics
5. Histologically or cytologically documented TCC/UC (transitional cell and mixed transitional/non-transitional cell histologies; pure variant histologies are not eligible) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) at
screening also meeting the following:
a. Unresectable, Stage IV disease (ie, T4b, any N; or any T, N2-N3 [Note: The Investigators will use their discretion to confirm the cause of N2 disease (reactive or inflammatory)]; or M1)
b. No prior systemic therapy for unresectable, Stage IV disease. Patients who have received a prior platinum-based regimen as definitive chemoradiation or adjuvant or neoadjuvant treatment administered with curative intent are eligible, provided
that disease relapse has occurred >12 months from completion of last therapy (for chemoradiation and adjuvant treatment) or >12 months from last oncologic surgery (for neoadjuvant treatment).
6. Ineligible for platinum-based chemotherapy defined as (i) in the opinion of the Investigator, unfit for carboplatin-based chemotherapy and (ii) meeting one of the following criteria:
a. CrCl <60 mL/min calculated by Cockcroft-Gault equation (using actual body weight) or by measured 24-hour urine collection. (In cases where both are performed, measured 24-hour urine collection will be used to determine eligibility.)
b. Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 audiometric hearing loss (25 dB in 2 consecutive wave ranges)
c. CTCAE Grade ≥2 peripheral neuropathy
d. New York Heart Association Class III heart failure (Criteria Committee NYHA 1964)
e. ECOG 2 (Oken et al 1982)
7. Known tumor HRR mutation status prior to randomization. Either de novo biopsies collected as part of routine clinical practice or archival tumor samples (taken ≤3 years prior to screening) are acceptable. Formalin-fixed, paraffin-embedded (FFPE) tumor
sample from the primary cancer must be available for central testing and should be of sufficient quantity to allow HRR mutation status, PD-L1 status, and other exploratory biomarker analyses.
8. World Health Organization (WHO)/ECOG performance status of 0, 1, or 2 at enrollment and randomization.
9. Patients with at least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to
randomization.
10. Life expectancy ≥12 weeks at randomization.
11. Adequate organ and marrow function as defined below:
a. Hemoglobin ≥10.0 g/dL
b. Absolute neutrophil count ≥1.5×109 /L
c. Platelet count ≥100×109 /L
d. Total bilirubin (TBL) ≤1.5× the upper limit of normal (ULN), unless due to Gilbert’s syndrome, who will be allowed in consultation with their physician and AstraZeneca.
e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN; for patients with hepatic metastases, ALT and AST ≤5× ULN Measured CrCl ≥31 mL/min by 24-hour urine collection or CrCl ≥31 mL/min calculated by Cockcroft-Gault equation (using actual body weight)
12. Ability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening, or otherwise altering the product formulation. Patients should not have GI illnesses that would preclude the absorption of olaparib, which is an oral agent.
13. Body weight >30 kg at enrollment and randomization.
14. Male or female.
15. Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
16. Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year
ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
Insurance Portability and Accountability Act in the US and EU Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
2. Provision of signed and dated, written ICF prior to any mandatory study-specific procedures, sampling, and analyses.
3. Provision of signed and dated, written genetic informed consent (optional) prior to collection of sample for genetic analysis.
The ICF process is described in Appendix A3.
4. 18 years or older, at the time of signing the ICF. For subjects aged <20 years and enrolled in Japan, a written ICF should be obtained from the subject and his or her legally acceptable representative.
Type of patient and disease characteristics
5. Histologically or cytologically documented TCC/UC (transitional cell and mixed transitional/non-transitional cell histologies; pure variant histologies are not eligible) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) at
screening also meeting the following:
a. Unresectable, Stage IV disease (ie, T4b, any N; or any T, N2-N3 [Note: The Investigators will use their discretion to confirm the cause of N2 disease (reactive or inflammatory)]; or M1)
b. No prior systemic therapy for unresectable, Stage IV disease. Patients who have received a prior platinum-based regimen as definitive chemoradiation or adjuvant or neoadjuvant treatment administered with curative intent are eligible, provided
that disease relapse has occurred >12 months from completion of last therapy (for chemoradiation and adjuvant treatment) or >12 months from last oncologic surgery (for neoadjuvant treatment).
6. Ineligible for platinum-based chemotherapy defined as (i) in the opinion of the Investigator, unfit for carboplatin-based chemotherapy and (ii) meeting one of the following criteria:
a. CrCl <60 mL/min calculated by Cockcroft-Gault equation (using actual body weight) or by measured 24-hour urine collection. (In cases where both are performed, measured 24-hour urine collection will be used to determine eligibility.)
b. Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 audiometric hearing loss (25 dB in 2 consecutive wave ranges)
c. CTCAE Grade ≥2 peripheral neuropathy
d. New York Heart Association Class III heart failure (Criteria Committee NYHA 1964)
e. ECOG 2 (Oken et al 1982)
7. Known tumor HRR mutation status prior to randomization. Either de novo biopsies collected as part of routine clinical practice or archival tumor samples (taken ≤3 years prior to screening) are acceptable. Formalin-fixed, paraffin-embedded (FFPE) tumor
sample from the primary cancer must be available for central testing and should be of sufficient quantity to allow HRR mutation status, PD-L1 status, and other exploratory biomarker analyses.
8. World Health Organization (WHO)/ECOG performance status of 0, 1, or 2 at enrollment and randomization.
9. Patients with at least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to
randomization.
10. Life expectancy ≥12 weeks at randomization.
11. Adequate organ and marrow function as defined below:
a. Hemoglobin ≥10.0 g/dL
b. Absolute neutrophil count ≥1.5×109 /L
c. Platelet count ≥100×109 /L
d. Total bilirubin (TBL) ≤1.5× the upper limit of normal (ULN), unless due to Gilbert’s syndrome, who will be allowed in consultation with their physician and AstraZeneca.
e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN; for patients with hepatic metastases, ALT and AST ≤5× ULN Measured CrCl ≥31 mL/min by 24-hour urine collection or CrCl ≥31 mL/min calculated by Cockcroft-Gault equation (using actual body weight)
12. Ability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening, or otherwise altering the product formulation. Patients should not have GI illnesses that would preclude the absorption of olaparib, which is an oral agent.
13. Body weight >30 kg at enrollment and randomization.
14. Male or female.
15. Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone
levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
16. Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year
ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
Exclusion Criteria
1. Active or prior documented autoimmune or inflammatory disorders (including but not limited to inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis
syndrome, Wegener syndrome [granulomatosis with polyangiitis], Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc.). The following are exceptions to this criterion:
a. Patients with vitiligo or alopecia.
b. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
c. Any chronic skin condition that does not require systemic therapy.
d. Patients without active disease in the last 3 years may be included but only after consultation with AstraZeneca.
e. Patients with celiac disease controlled by diet alone may be included but only after consultation with AstraZeneca.
2. Other invasive malignancy within 5 years before the first dose of the IP, except for the following pending a discussion with AstraZeneca:
a. Patients with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression and who in the opinion of the Investigator are not deemed to require active intervention
b. Patients who have been adequately treated for a malignancy with a low potential risk for recurrence (eg, cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or ductal carcinoma in situ of the breast that has been surgically cured).
3. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of the IP. Local surgery of isolated lesions for palliative intent is acceptable.
4. Brain metastases or spinal cord compression unless the patient’s condition is stable (asymptomatic; no evidence of new or emerging brain metastases) and off steroid for at least 14 days prior to the start of the IP. Following radiotherapy and/or surgery,
patients with brain metastases must wait 4 weeks after the intervention and must confirm stable condition using imaging before randomization.
5. History of active primary immunodeficiency.
6. Active infection including tuberculosis (TB) (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen [HBsAg] result),
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
7. History of allogenic organ transplantation.
8. Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic GI
conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
9. Prior exposure to a PARP inhibitor or immune-mediated therapy (with exclusion of Bacillus Calmette Guerin [BCG]), including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer
vaccines. Prior local intravesical chemotherapy or BCG is allowed if completed at least 28 days prior to the initiation of study treatment.
10. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
11. Current or prior use of immunosuppressive medication within 14 days before the first dose of the IP. The following are exceptions to this criterion:
a. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
12. Concomitant use of known strong cytochrome P450 (CYP) 3A (CYP3A) inhibitors (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, and telaprevir) or moderate CYP3A inhibitors (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, and verapamil). The required washout period prior to starting study treatment is 2 weeks.
13. 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, and modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
14. No radiation therapy is allowed, unless it is (1) definitive radiation that had been administered at least 12 months prior; (2) palliative radiation to the brain, with associated criteria for stability or lack of symptoms; or (3) palliative radiation to
painful bony lesions (this must comprise less than 30% of the bone marrow) or symptomatic pelvic soft tissue mass(es).
15. Receipt of live attenuated vaccine within 30 days prior to the first dose of the IP. Note: Patients, if enrolled, should not receive live vaccine while receiving the IP and up to 30 days after the last dose of the IP.
16. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
17. Previous IP assignment in the present study or previous exclusion at randomization.
18. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
19. Patients with a known hypersensitivity to durvalumab, olaparib, or any of the excipients of the products.
20. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
21. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab.
syndrome, Wegener syndrome [granulomatosis with polyangiitis], Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc.). The following are exceptions to this criterion:
a. Patients with vitiligo or alopecia.
b. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement.
c. Any chronic skin condition that does not require systemic therapy.
d. Patients without active disease in the last 3 years may be included but only after consultation with AstraZeneca.
e. Patients with celiac disease controlled by diet alone may be included but only after consultation with AstraZeneca.
2. Other invasive malignancy within 5 years before the first dose of the IP, except for the following pending a discussion with AstraZeneca:
a. Patients with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression and who in the opinion of the Investigator are not deemed to require active intervention
b. Patients who have been adequately treated for a malignancy with a low potential risk for recurrence (eg, cervical carcinoma in situ, non-melanomatous carcinoma of the skin, or ductal carcinoma in situ of the breast that has been surgically cured).
3. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of the IP. Local surgery of isolated lesions for palliative intent is acceptable.
4. Brain metastases or spinal cord compression unless the patient’s condition is stable (asymptomatic; no evidence of new or emerging brain metastases) and off steroid for at least 14 days prior to the start of the IP. Following radiotherapy and/or surgery,
patients with brain metastases must wait 4 weeks after the intervention and must confirm stable condition using imaging before randomization.
5. History of active primary immunodeficiency.
6. Active infection including tuberculosis (TB) (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen [HBsAg] result),
hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
7. History of allogenic organ transplantation.
8. Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic GI
conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
9. Prior exposure to a PARP inhibitor or immune-mediated therapy (with exclusion of Bacillus Calmette Guerin [BCG]), including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer
vaccines. Prior local intravesical chemotherapy or BCG is allowed if completed at least 28 days prior to the initiation of study treatment.
10. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
11. Current or prior use of immunosuppressive medication within 14 days before the first dose of the IP. The following are exceptions to this criterion:
a. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
12. Concomitant use of known strong cytochrome P450 (CYP) 3A (CYP3A) inhibitors (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, and telaprevir) or moderate CYP3A inhibitors (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, and verapamil). The required washout period prior to starting study treatment is 2 weeks.
13. 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, and modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
14. No radiation therapy is allowed, unless it is (1) definitive radiation that had been administered at least 12 months prior; (2) palliative radiation to the brain, with associated criteria for stability or lack of symptoms; or (3) palliative radiation to
painful bony lesions (this must comprise less than 30% of the bone marrow) or symptomatic pelvic soft tissue mass(es).
15. Receipt of live attenuated vaccine within 30 days prior to the first dose of the IP. Note: Patients, if enrolled, should not receive live vaccine while receiving the IP and up to 30 days after the last dose of the IP.
16. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
17. Previous IP assignment in the present study or previous exclusion at randomization.
18. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study.
19. Patients with a known hypersensitivity to durvalumab, olaparib, or any of the excipients of the products.
20. Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
21. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab.
The Estimated Number of Participants
-
Taiwan
125 participants
-
Global
375 participants
