Clinical Trials List
Protocol NumberD9722C00001
Active
2024-07-31 - 2031-12-31
Phase III
Recruiting7
ICD-10C50.011
Malignant neoplasm of nipple and areola, right female breast
ICD-10C50.012
Malignant neoplasm of nipple and areola, left female breast
ICD-10C50.019
Malignant neoplasm of nipple and areola, unspecified female breast
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9174.0
Malignant neoplasm of female breast, nipple and areola
A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant compared with Physician’s Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients with BRCA1, BRCA2 or PALB2 Mutations and Hormone Receptor-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH non-amplified) Advanced Breast Cancer (EvoPAR-Breast01)
-
Trial Applicant
-
Sponsor
AstraZeneca AB,
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Chen-Teng Wu 無
- Liang-Chih Liu 無
- 黃至豪 無
- 蘇孟夏 無
- Chih-Jung Chen 無
- Yao-Chung Wu 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 黃怡菁 無
- Zhu-Jun Loh 無
- Shang-Hung Chen 無
- Kuo-Ting Lee 無
- Jui-Hung Tsai 無
- Chun-Hui Lee 無
- 楊舜如 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 陳彥蓁 Division of General Surgery
- Ta-Chung Chao Division of Hematology & Oncology
- 賴亦貞 無
- 邱仁輝 Division of General Surgery
- 馮晉榮 無
- 鄭涵方 無
- 林燕淑 無
- Yi-Fang Tsai 無
- 郭懿萱 無
- Chi-Cheng Huang Division of General Surgery
- 陳柏芳 Division of General Surgery
- Chun-Yu Liu 無
- Jiun-I Lai 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 沈士哲 無
- Yung-Chang Lin Division of Hematology & Oncology
- Chan-Keng Yang Division of Hematology & Oncology
- 周旭桓 無
- Chi-Chang Yu Division of General Surgery
- 阮昱翔 Division of Radiology
- Mengting Peng 無
- Wen-Chi Shen Division of Hematology & Oncology
- Wen-Ling Kuo 無
- Chun-Hsiu Liu 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Wei-Hong Cheng
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
BRCA1, BRCA2 or PALB2 Mutations and Hormone Receptor-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH non-amplified) Advanced Breast Cancer (EvoPAR-Breast01)
Objectives
To demonstrate the superiority of saruparib (AZD5305) + camizestrant relative to physician’s choice CDK4/6i + ET, by assessment of PFS.
Test Drug
tablets
tablets
tablets
Active Ingredient
Saruparib (AZD5305), Film-Coated tablets
Camizestran(AZD9833) Film-Coated Tablet
Camizestran(AZD9833) Film-Coated Tablet
Dosage Form
116
116
116
Dosage
MG
Endpoints
PFS is defined as time from randomisation until progression per RECIST v1.1 as assessed by BICR, or death due to any cause.
The analysis will include all randomised participants. All events will be included regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST v1.1 progression.
However, if the participant progresses or dies immediately after two or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the two missed visits.
The measure of interest is the hazard ratio of PFS.
The analysis will include all randomised participants. All events will be included regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy, or clinically progresses prior to RECIST v1.1 progression.
However, if the participant progresses or dies immediately after two or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the two missed visits.
The measure of interest is the hazard ratio of PFS.
Inclution Criteria
1. You must be ≥ 18 years old when signing the participant consent form.
2. Premenopausal/menopausal transitional and/or postmenopausal adult women, and adult men:
(a) Premenopausal/menopausal transitional women (i.e., those who do not meet the following definition of postmenopause) may be included if they are suitable for luteinizing hormone-releasing hormone (LHRH) agonist therapy. You must have started concomitant LHRH agonist therapy before or on day 1 of cycle 1 and must be willing to continue treatment during the trial.
(b) Postmenopausal women are defined as:
(i) aged ≥ 60 years, or
(ii) aged < 60 years, and have discontinued all exogenous hormone therapy/chemotherapy/ovarian suppression/tamoxifen or similar drugs for at least 12 months. Your serum estradiol and follicle-stimulating hormone (FSH) levels should also be confirmed to be within the standard laboratory reference range for postmenopausal women, or
(iii) a history of bilateral oophorectomy.
If you are male, you may be included if you are eligible for luteinizing hormone-releasing hormone (LH) agonist therapy, unless you have a clear history of orchiectomy. You must have started LH agonist concomitant therapy before or on day 1 of cycle 1 and must be willing to continue treatment during the trial.
Participant Type and Disease Characteristics
3. Based on local laboratory test results, histological or cytological data indicate a diagnosis of hormone receptor-positive, human epidermal growth factor receptor type 2 (HGF-2)-negative breast cancer.
(a) Data from the most recent tumor section evaluation showing >1% estrogen receptor-positive cells, using analytical methods conforming to the American Society of Clinical Oncology Certified Analytics Professional (ASCO CAP 2020) guidelines.
(b) Based on the most recent local examination of tumor sections, data indicate a type 2 human epidermal growth factor receptor (HGF-2) negative tumor: According to the 2018 American Society of Clinical Oncology (ASCO) Certification Analytical Professional Guidelines, an HGF-2 negative tumor is defined as having an immunohistochemistry (IHC) score of 0/1+, or being negative using in situ hybridization methods (fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH), silver in situ hybridization (SISH), or dual color in situ hybridization (DISH)), defined as an HGF-2/CEP17 ratio < 2, or an HGF-2 copy number assessed by a single probe < 4.
4. Advanced breast cancer with locally advanced or metastatic disease that is ineligible for curative treatment. You must have at least one lesion (measurable and/or non-measurable) that can be properly assessed by computed tomography (CT) at baseline (or magnetic resonance imaging (MRI) if CT is not possible) and is suitable for repeat assessment according to the Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1).
5. Your Eastern Cooperative Oncology Group (ECOG) performance status score is 0 or 1, and you have not shown any progression within 2 weeks prior to the screening baseline and before randomization.
6. Your minimum life expectancy is 12 weeks.
7. According to the Central Laboratory Services Manual, your formalin-fixed and paraffin-embedded (FFPE) tumor tissue is required. A written confirmation of available formalin-fixed paraffin-embedded tumor specimens should be provided to meet the randomization requirements of the trial.
8. You must:
(a) have data showing a loss-of-function mutation in the gene for breast cancer susceptibility gene 1, breast cancer susceptibility gene 2, or a partner and localizing protein gene of breast cancer susceptibility gene 2, based on local testing conducted by a Clinical Laboratory Improvement (CLIA)/Certified Analytics Professional (CAP) accredited laboratory (USA), a local accredited laboratory (outside the US), or a qualified laboratory approved by the trial client (China only). You may be randomly assigned to the trial based on your known germline status, or
(b) have a loss-of-function mutation in the gene for breast cancer susceptibility gene 1, breast cancer susceptibility gene 2, or a partner and localizing protein gene of breast cancer susceptibility gene 2, as confirmed by a central organization.
9. Adequate organ and bone marrow function, as described below:
(a) Hemoglobin ≥ 10.0 g/dL without transfusion within 14 days prior to randomization
(b) Absolute neutrophil count ≥ 1.5 × 10⁹/L without growth factor administration within 28 days prior to randomization
(c) Platelet count ≥ 100 × 10⁹/L
(d) Serum albumin ≥ 3.0 g/dL
(e) International normalized ratio (INR) ≤ 1.5. If you are receiving oral anticoagulants, you may be included if your INR is < 2. You should be excluded if you have a clinical cause of an elevated INR, such as bleeding disorders or impaired hepatic synthesis.
(f) Total bilirubin ≤ 1.5 × upper limit of normal (ULN), or ≤ 3 × ULN if there is a documented history of Gilbert's syndrome (unconjugated hyperbilirubinemia).
(g) Alanine aminotransferase/transaminase (ALT) and aspartate aminotransferase/transaminase (AST) ≤ 2.5 × ULN; if you have liver metastases, ALT and AST ≤ 5 × ULN.
(h) Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m² according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
• If your (if you are male) serum creatinine (SCr) is ≤ 0.9 mg/dL (≤ 79.56 μmol/L), please use the following formula: 142 x (serum creatinine/0.9) - 0.302 x 0.9938 age (years)
• If your (if you are male) serum creatinine is > 0.9 mg/dL (> 79.56 μmol/L), please use the following formula: 142 x (serum creatinine/0.9) - 1.200 x 0.9938 age (years)
• If your (if you are female) serum creatinine is < 0.7 mg/dL, please use the following formula:
142 x (serum creatinine/0.7) - 0.241 x 0.9938 Age (years) x 1.012
• If your (if you are female) serum creatinine is > 0.7 mg/dL, please use the following formula:
142 x (serum creatinine/0.7) - 1.200 x 0.9938 Age (years) x 1.012
Reproductive Aspects
10. Women who are not menopausal or have not undergone a hysterectomy must have data showing a negative pregnancy test result within 28 days prior to randomization.
11. If you are of fertility:
(a) Pregnancy test results must be negative at screening and before each treatment cycle.
(b) If you are having sexual intercourse with an unsterilized male partner, you must use at least one highly effective method of contraception* plus a barrier method (e.g., condoms with spermicide [according to local guidelines]) from the date of signing the participant consent form until approximately 6 months after the last dose of the trial treatment.
* Hormonal contraception is not permitted.
(c) From the screening period until approximately 6 months after the last dose of the trial treatment, you must not breastfeed, and you must not donate or have your eggs collected for your own use.
12. If you are a male participant:
(a) From the screening period until approximately 6 months after receiving the last dose of the trial treatment, you must use condoms (with spermicide [according to local guidelines]) with all sexual partners. If you are a fertile female partner, you should use a highly effective method of contraception throughout this period.
(b) During the trial period and for approximately 6 months after the last dose of the trial treatment, you must avoid impregnating others or donating sperm.
Informed Consent
13. The ability to provide signed participant consent forms, including compliance with the requirements and limitations listed therein.
14. Before collecting specimens for selective genomic studies to support the genomics project, providing signed and dated selective genomics project research information and consent forms.
2. Premenopausal/menopausal transitional and/or postmenopausal adult women, and adult men:
(a) Premenopausal/menopausal transitional women (i.e., those who do not meet the following definition of postmenopause) may be included if they are suitable for luteinizing hormone-releasing hormone (LHRH) agonist therapy. You must have started concomitant LHRH agonist therapy before or on day 1 of cycle 1 and must be willing to continue treatment during the trial.
(b) Postmenopausal women are defined as:
(i) aged ≥ 60 years, or
(ii) aged < 60 years, and have discontinued all exogenous hormone therapy/chemotherapy/ovarian suppression/tamoxifen or similar drugs for at least 12 months. Your serum estradiol and follicle-stimulating hormone (FSH) levels should also be confirmed to be within the standard laboratory reference range for postmenopausal women, or
(iii) a history of bilateral oophorectomy.
If you are male, you may be included if you are eligible for luteinizing hormone-releasing hormone (LH) agonist therapy, unless you have a clear history of orchiectomy. You must have started LH agonist concomitant therapy before or on day 1 of cycle 1 and must be willing to continue treatment during the trial.
Participant Type and Disease Characteristics
3. Based on local laboratory test results, histological or cytological data indicate a diagnosis of hormone receptor-positive, human epidermal growth factor receptor type 2 (HGF-2)-negative breast cancer.
(a) Data from the most recent tumor section evaluation showing >1% estrogen receptor-positive cells, using analytical methods conforming to the American Society of Clinical Oncology Certified Analytics Professional (ASCO CAP 2020) guidelines.
(b) Based on the most recent local examination of tumor sections, data indicate a type 2 human epidermal growth factor receptor (HGF-2) negative tumor: According to the 2018 American Society of Clinical Oncology (ASCO) Certification Analytical Professional Guidelines, an HGF-2 negative tumor is defined as having an immunohistochemistry (IHC) score of 0/1+, or being negative using in situ hybridization methods (fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH), silver in situ hybridization (SISH), or dual color in situ hybridization (DISH)), defined as an HGF-2/CEP17 ratio < 2, or an HGF-2 copy number assessed by a single probe < 4.
4. Advanced breast cancer with locally advanced or metastatic disease that is ineligible for curative treatment. You must have at least one lesion (measurable and/or non-measurable) that can be properly assessed by computed tomography (CT) at baseline (or magnetic resonance imaging (MRI) if CT is not possible) and is suitable for repeat assessment according to the Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1).
5. Your Eastern Cooperative Oncology Group (ECOG) performance status score is 0 or 1, and you have not shown any progression within 2 weeks prior to the screening baseline and before randomization.
6. Your minimum life expectancy is 12 weeks.
7. According to the Central Laboratory Services Manual, your formalin-fixed and paraffin-embedded (FFPE) tumor tissue is required. A written confirmation of available formalin-fixed paraffin-embedded tumor specimens should be provided to meet the randomization requirements of the trial.
8. You must:
(a) have data showing a loss-of-function mutation in the gene for breast cancer susceptibility gene 1, breast cancer susceptibility gene 2, or a partner and localizing protein gene of breast cancer susceptibility gene 2, based on local testing conducted by a Clinical Laboratory Improvement (CLIA)/Certified Analytics Professional (CAP) accredited laboratory (USA), a local accredited laboratory (outside the US), or a qualified laboratory approved by the trial client (China only). You may be randomly assigned to the trial based on your known germline status, or
(b) have a loss-of-function mutation in the gene for breast cancer susceptibility gene 1, breast cancer susceptibility gene 2, or a partner and localizing protein gene of breast cancer susceptibility gene 2, as confirmed by a central organization.
9. Adequate organ and bone marrow function, as described below:
(a) Hemoglobin ≥ 10.0 g/dL without transfusion within 14 days prior to randomization
(b) Absolute neutrophil count ≥ 1.5 × 10⁹/L without growth factor administration within 28 days prior to randomization
(c) Platelet count ≥ 100 × 10⁹/L
(d) Serum albumin ≥ 3.0 g/dL
(e) International normalized ratio (INR) ≤ 1.5. If you are receiving oral anticoagulants, you may be included if your INR is < 2. You should be excluded if you have a clinical cause of an elevated INR, such as bleeding disorders or impaired hepatic synthesis.
(f) Total bilirubin ≤ 1.5 × upper limit of normal (ULN), or ≤ 3 × ULN if there is a documented history of Gilbert's syndrome (unconjugated hyperbilirubinemia).
(g) Alanine aminotransferase/transaminase (ALT) and aspartate aminotransferase/transaminase (AST) ≤ 2.5 × ULN; if you have liver metastases, ALT and AST ≤ 5 × ULN.
(h) Estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m² according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
• If your (if you are male) serum creatinine (SCr) is ≤ 0.9 mg/dL (≤ 79.56 μmol/L), please use the following formula: 142 x (serum creatinine/0.9) - 0.302 x 0.9938 age (years)
• If your (if you are male) serum creatinine is > 0.9 mg/dL (> 79.56 μmol/L), please use the following formula: 142 x (serum creatinine/0.9) - 1.200 x 0.9938 age (years)
• If your (if you are female) serum creatinine is < 0.7 mg/dL, please use the following formula:
142 x (serum creatinine/0.7) - 0.241 x 0.9938 Age (years) x 1.012
• If your (if you are female) serum creatinine is > 0.7 mg/dL, please use the following formula:
142 x (serum creatinine/0.7) - 1.200 x 0.9938 Age (years) x 1.012
Reproductive Aspects
10. Women who are not menopausal or have not undergone a hysterectomy must have data showing a negative pregnancy test result within 28 days prior to randomization.
11. If you are of fertility:
(a) Pregnancy test results must be negative at screening and before each treatment cycle.
(b) If you are having sexual intercourse with an unsterilized male partner, you must use at least one highly effective method of contraception* plus a barrier method (e.g., condoms with spermicide [according to local guidelines]) from the date of signing the participant consent form until approximately 6 months after the last dose of the trial treatment.
* Hormonal contraception is not permitted.
(c) From the screening period until approximately 6 months after the last dose of the trial treatment, you must not breastfeed, and you must not donate or have your eggs collected for your own use.
12. If you are a male participant:
(a) From the screening period until approximately 6 months after receiving the last dose of the trial treatment, you must use condoms (with spermicide [according to local guidelines]) with all sexual partners. If you are a fertile female partner, you should use a highly effective method of contraception throughout this period.
(b) During the trial period and for approximately 6 months after the last dose of the trial treatment, you must avoid impregnating others or donating sperm.
Informed Consent
13. The ability to provide signed participant consent forms, including compliance with the requirements and limitations listed therein.
14. Before collecting specimens for selective genomic studies to support the genomics project, providing signed and dated selective genomics project research information and consent forms.
Exclusion Criteria
You are ineligible to participate in the trial if you meet any of the following criteria: Medical Conditions
1. A history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), or features consistent with MDS/AML (based on prior diagnostic studies). Specific screening for MDS/AML is not required.
2. Any known bleeding tendency (e.g., active peptic ulcer, recent hemorrhagic stroke within the last 6 months, proliferative diabetic retinopathy).
3. A history of severe cytopenia lasting >2 weeks for any cause (e.g., absolute neutrophil count (ANC) < 0.5 × 10⁹/L or platelet count < 50 × 10⁹/L). 4. Based on the investigator's judgment, you have any evidence of severe or uncontrolled systemic disease or active uncontrolled infection, including but not limited to uncontrolled major epilepsy and active bleeding disorders, unstable spinal cord compression, superior vena cava syndrome, high-resolution computed tomography (HRCT) showing extensive interstitial bilateral lung disease, or a history of allogeneic organ transplantation, which the investigator deems unsuitable for participation in this trial or will affect your adherence to the trial protocol.
5. Refractory nausea and vomiting, chronic gastrointestinal (GI) disease, inability to swallow formulated medications, or a previous extensive bowel resection that may impair the absorption, distribution, metabolism, or elimination of the investigational drug.
6. A history of another primary malignancy. Exceptions include:
(a) Fully excised non-melanoma skin cancer
(b) In situ disease already treated with curative therapy
(c) Malignant tumors that have received curative therapy ≥ 2 years prior to the first dose of trial treatment and have no known active disease during treatment
7. Persistent toxicity from prior anticancer therapy (Common Terminology Criteria for Adverse Events (CTCAE) ≥ Grade 2), excluding hair loss. If you have toxicity that the trial administrator deems reasonably not likely to affect your safety during the trial treatment (e.g., hormone therapy-related side effects), you may be included with the consent of the trial clinical supervisor.
8. Spinal cord compression, brain metastases, carcinomatous meningitis, or leptomeningeal disease, unless clearly treated with local therapy, asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to starting trial treatment. There must be at least a 2-week interval between the completion of brain radiation therapy and trial inclusion.
Medical Condition – Infection
9. Evidence of active and uncontrolled hepatitis B and/or hepatitis C. Hepatitis B and hepatitis C screening is not required. If you have been previously exposed to hepatitis B or hepatitis C, you are eligible if you meet one of the following criteria:
(a) Negative results for hepatitis B surface antigen (HBsAg) and anti-chronic hepatitis B antibody (anti-HBc), or
(b) Positive for hepatitis B surface antigen and anti-chronic hepatitis B core antibody, and meeting criteria i through iii:
(i) Hepatitis B virus (HBV) viral load < 2000 IU/L.
(ii) Normal transaminase levels, or, if liver metastases are present, abnormal transaminase levels not caused by hepatitis B virus infection (i.e., aspartate transaminase/alanine transaminase < 3 × upper limit of normal).
(iii) Initiation of antiviral therapy at least 2 weeks prior to the first dose of trial treatment and maintenance of antiviral therapy throughout the treatment period.
(c) Positive anti-chronic hepatitis B antibody, negative hepatitis B surface antigen, and hepatitis B virus deoxyribonucleic acid (HCV) < 2000 IU/L.
(d) If your hepatitis C virus (HCV) antibody test result is positive, eligibility is only possible if the polymerase chain reaction (PCR) test result for hepatitis C virus ribonucleic acid (RNA) is negative.
Note: We should carefully consider your inclusion if you have unavailable hepatology services and/or currently require antiviral therapy.
10. Evidence of active and uncontrolled human immunodeficiency virus (HIV) infection. If you have a controlled HIV infection, you must meet the following criteria:
(a) Undetectable viral RNA levels (less than 400 copies/mL) within 4 weeks prior to the first dose of trial treatment;
(b) Cluster of differentiation 4 receptor (CD4+) count ≥ 350 cells/μL;
(c) No history of opportunistic infection with acquired immunodeficiency syndrome (AIDS) within the past 12 months; and
(d) Stable use of the same anti-HIV medication for at least 6 months.
HIV screening is not required.
11. Open tuberculosis infection (clinical evaluation may include clinical history, physical examination, and radiographic abnormalities, or tuberculosis testing consistent with local practice). Medical Conditions - Cardiac Aspects
12. During screening, the QT interval corrected using Fridericia’s formula (QTcF) could not be confirmed on the electrocardiogram (ECG) (i.e., it was unreadable or uninterpretable).
13. The average resting-corrected QT interval (Fridericia-corrected QT interval) of three ECGs recorded at 5-minute intervals during screening is >470 ms, unless you are planned to be assigned to receive ribociclib. In this case, a Fridericia-corrected QT interval >450 ms is an exclusion criterion (using Fridericia formula correction).
14. Resting heart rate <55 bpm if you are using concomitant medications to reduce your heart rate; or have a history of stroke, uncontrolled coronary heart disease, or arrhythmia. Repeated measurements are allowed during screening.
15. Any factors that increase the risk of QT interval prolongation (QTc) or arrhythmic events, such as symptomatic heart failure, congenital long QT syndrome, a family history of long QT syndrome, a history of unexplained sudden cardiac death before age 40, or use of any concomitant medications known to prolong the QT interval, hypertrophic cardiomyopathy, clinically significant stenotic valvular disease, clinically significant hypokalemia, hyperkalemia, hypomagnesemia and hypermagnesemia, hypocalcemia and hypercalcemia. Electrolyte abnormalities may be corrected to normal during screening.
16. Any clinically significant abnormalities in the rhythm, conduction, or morphology of the resting electrocardiogram, such as third-degree heart block.
17. Left ventricular ejection fraction < 50% as measured by echocardiography or multigated acquisition (MUGA) at screening (or based on an assessment performed within 4 months prior to randomization), and New York Heart Association (NYHA) grade 2 or higher congestive heart failure.
18. Uncontrolled hypertension. Having hypertension may qualify you, but your blood pressure must be adequately controlled at baseline. You may be subject to rescreening regarding blood pressure requirements.
19. An episode of acute coronary syndrome/acute myocardial infarction, unstable angina, coronary intervention procedures (percutaneous coronary intervention or coronary artery bypass surgery), angioplasty, or stenting within the past 6 months.
Pre- or concomitant therapies not permitted.
20. Patients receiving exogenous reproductive hormone therapy (e.g., birth control pills, hormone replacement therapy, Mirena intrauterine devices, or megestrol acetate) or non-local hormone therapy to treat a non-cancer-related condition (e.g., hormone replacement therapy).
21. Patients who have undergone major surgical procedures (excluding vascular access placement) or experienced significant trauma within 4 weeks prior to the first dose of trial treatment, or who are expected to undergo major surgery during the trial. You should have fully recovered from any clinically significant adverse events.
22. Patients who have received palliative radiation therapy with a limited field of radiation within 2 weeks prior to the first dose of trial treatment, or palliative radiation therapy with a wide field of radiation or more than 30% of the bone marrow within 4 weeks prior to the first dose of trial treatment. You should have fully recovered from any clinically significant adverse events.
23. Patients who have received systemic anticancer therapy for locally recurrent or metastatic disease are not permitted, except for endocrine therapy (ET) treatment within a maximum of 28 days prior to randomization.
24. Received blood product support or growth factor support within 28 days.
25. Concurrent use of any systemic anticancer therapy.
26. Concurrent use of the following types of drugs or herbal supplements within 21 days prior to randomization or for at least 5 half-lives (whichever is longer):
(a) Potent and intermediate inducers/inhibitors of cytochrome P450 3A4 (CYP3A4)
(b) Sensitive cytochrome P450 2B6 (CYP2B6) receptors
(c) Treatment-index narrowed cytochrome P450 2C9 (CYP2C9) and/or cytochrome P450 2C19 (CYP2C19) receptors, such as warfarin (and other coumarin-derived vitamin K antagonist anticoagulants) and phenytoin.
The above includes, but is not limited to:
27. Use of medications known to prolong the QT interval and with a known risk of multiform ventricular arrhythmias (torsades de pointes, TdP).
28. Systemic use of atropine.
29. The following exclusion criteria apply to the treatment of early-stage breast cancer:
(a) Disease progression within ≤ 84 days after the last dose of pre-adjuvant or adjuvant chemotherapy
(b) Disease progression within ≤ 1 year (365 days) after treatment with a poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi) and/or platinum-based drugs for early-stage breast cancer
(c) Disease progression within ≤ 1 year (365 days) after the last dose of a cyclin-dependent kinase inhibitor 4/6 (CDK4/6i) under adjuvant therapy conditions
(d) Disease progression within ≤ 1 year (365 days) after the last dose of an oral selective estrogen receptor degrader (including camizestrant).
Other exclusion criteria:
30. Concurrent enrollment in another clinical trial (unless that trial is non-invasive, or you are in the follow-up period of an invasive trial).
31. You are known to have a hypersensitivity to saruparib (AZD5305), any investigational drug in the trial, or any excipients of these drugs.
32. Participation in the planning and/or execution of this trial (applicable to AstraZeneca employees and/or trial center personnel).
33. You should not participate in the trial if the trial administrator determines that you are unlikely to comply with the trial procedures, limitations, and requirements.
34. You have previously been randomly assigned to this trial.
35. Applicable only to women who are currently pregnant (confirmed by a positive pregnancy test) or breastfeeding, or planning to conceive.
Note: If your hepatitis B virus, hepatitis C virus, human immunodeficiency virus, or tuberculosis (TB) test results are positive (including false positives), the hospital will report to the relevant authorities in accordance with the law.
1. A history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), or features consistent with MDS/AML (based on prior diagnostic studies). Specific screening for MDS/AML is not required.
2. Any known bleeding tendency (e.g., active peptic ulcer, recent hemorrhagic stroke within the last 6 months, proliferative diabetic retinopathy).
3. A history of severe cytopenia lasting >2 weeks for any cause (e.g., absolute neutrophil count (ANC) < 0.5 × 10⁹/L or platelet count < 50 × 10⁹/L). 4. Based on the investigator's judgment, you have any evidence of severe or uncontrolled systemic disease or active uncontrolled infection, including but not limited to uncontrolled major epilepsy and active bleeding disorders, unstable spinal cord compression, superior vena cava syndrome, high-resolution computed tomography (HRCT) showing extensive interstitial bilateral lung disease, or a history of allogeneic organ transplantation, which the investigator deems unsuitable for participation in this trial or will affect your adherence to the trial protocol.
5. Refractory nausea and vomiting, chronic gastrointestinal (GI) disease, inability to swallow formulated medications, or a previous extensive bowel resection that may impair the absorption, distribution, metabolism, or elimination of the investigational drug.
6. A history of another primary malignancy. Exceptions include:
(a) Fully excised non-melanoma skin cancer
(b) In situ disease already treated with curative therapy
(c) Malignant tumors that have received curative therapy ≥ 2 years prior to the first dose of trial treatment and have no known active disease during treatment
7. Persistent toxicity from prior anticancer therapy (Common Terminology Criteria for Adverse Events (CTCAE) ≥ Grade 2), excluding hair loss. If you have toxicity that the trial administrator deems reasonably not likely to affect your safety during the trial treatment (e.g., hormone therapy-related side effects), you may be included with the consent of the trial clinical supervisor.
8. Spinal cord compression, brain metastases, carcinomatous meningitis, or leptomeningeal disease, unless clearly treated with local therapy, asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to starting trial treatment. There must be at least a 2-week interval between the completion of brain radiation therapy and trial inclusion.
Medical Condition – Infection
9. Evidence of active and uncontrolled hepatitis B and/or hepatitis C. Hepatitis B and hepatitis C screening is not required. If you have been previously exposed to hepatitis B or hepatitis C, you are eligible if you meet one of the following criteria:
(a) Negative results for hepatitis B surface antigen (HBsAg) and anti-chronic hepatitis B antibody (anti-HBc), or
(b) Positive for hepatitis B surface antigen and anti-chronic hepatitis B core antibody, and meeting criteria i through iii:
(i) Hepatitis B virus (HBV) viral load < 2000 IU/L.
(ii) Normal transaminase levels, or, if liver metastases are present, abnormal transaminase levels not caused by hepatitis B virus infection (i.e., aspartate transaminase/alanine transaminase < 3 × upper limit of normal).
(iii) Initiation of antiviral therapy at least 2 weeks prior to the first dose of trial treatment and maintenance of antiviral therapy throughout the treatment period.
(c) Positive anti-chronic hepatitis B antibody, negative hepatitis B surface antigen, and hepatitis B virus deoxyribonucleic acid (HCV) < 2000 IU/L.
(d) If your hepatitis C virus (HCV) antibody test result is positive, eligibility is only possible if the polymerase chain reaction (PCR) test result for hepatitis C virus ribonucleic acid (RNA) is negative.
Note: We should carefully consider your inclusion if you have unavailable hepatology services and/or currently require antiviral therapy.
10. Evidence of active and uncontrolled human immunodeficiency virus (HIV) infection. If you have a controlled HIV infection, you must meet the following criteria:
(a) Undetectable viral RNA levels (less than 400 copies/mL) within 4 weeks prior to the first dose of trial treatment;
(b) Cluster of differentiation 4 receptor (CD4+) count ≥ 350 cells/μL;
(c) No history of opportunistic infection with acquired immunodeficiency syndrome (AIDS) within the past 12 months; and
(d) Stable use of the same anti-HIV medication for at least 6 months.
HIV screening is not required.
11. Open tuberculosis infection (clinical evaluation may include clinical history, physical examination, and radiographic abnormalities, or tuberculosis testing consistent with local practice). Medical Conditions - Cardiac Aspects
12. During screening, the QT interval corrected using Fridericia’s formula (QTcF) could not be confirmed on the electrocardiogram (ECG) (i.e., it was unreadable or uninterpretable).
13. The average resting-corrected QT interval (Fridericia-corrected QT interval) of three ECGs recorded at 5-minute intervals during screening is >470 ms, unless you are planned to be assigned to receive ribociclib. In this case, a Fridericia-corrected QT interval >450 ms is an exclusion criterion (using Fridericia formula correction).
14. Resting heart rate <55 bpm if you are using concomitant medications to reduce your heart rate; or have a history of stroke, uncontrolled coronary heart disease, or arrhythmia. Repeated measurements are allowed during screening.
15. Any factors that increase the risk of QT interval prolongation (QTc) or arrhythmic events, such as symptomatic heart failure, congenital long QT syndrome, a family history of long QT syndrome, a history of unexplained sudden cardiac death before age 40, or use of any concomitant medications known to prolong the QT interval, hypertrophic cardiomyopathy, clinically significant stenotic valvular disease, clinically significant hypokalemia, hyperkalemia, hypomagnesemia and hypermagnesemia, hypocalcemia and hypercalcemia. Electrolyte abnormalities may be corrected to normal during screening.
16. Any clinically significant abnormalities in the rhythm, conduction, or morphology of the resting electrocardiogram, such as third-degree heart block.
17. Left ventricular ejection fraction < 50% as measured by echocardiography or multigated acquisition (MUGA) at screening (or based on an assessment performed within 4 months prior to randomization), and New York Heart Association (NYHA) grade 2 or higher congestive heart failure.
18. Uncontrolled hypertension. Having hypertension may qualify you, but your blood pressure must be adequately controlled at baseline. You may be subject to rescreening regarding blood pressure requirements.
19. An episode of acute coronary syndrome/acute myocardial infarction, unstable angina, coronary intervention procedures (percutaneous coronary intervention or coronary artery bypass surgery), angioplasty, or stenting within the past 6 months.
Pre- or concomitant therapies not permitted.
20. Patients receiving exogenous reproductive hormone therapy (e.g., birth control pills, hormone replacement therapy, Mirena intrauterine devices, or megestrol acetate) or non-local hormone therapy to treat a non-cancer-related condition (e.g., hormone replacement therapy).
21. Patients who have undergone major surgical procedures (excluding vascular access placement) or experienced significant trauma within 4 weeks prior to the first dose of trial treatment, or who are expected to undergo major surgery during the trial. You should have fully recovered from any clinically significant adverse events.
22. Patients who have received palliative radiation therapy with a limited field of radiation within 2 weeks prior to the first dose of trial treatment, or palliative radiation therapy with a wide field of radiation or more than 30% of the bone marrow within 4 weeks prior to the first dose of trial treatment. You should have fully recovered from any clinically significant adverse events.
23. Patients who have received systemic anticancer therapy for locally recurrent or metastatic disease are not permitted, except for endocrine therapy (ET) treatment within a maximum of 28 days prior to randomization.
24. Received blood product support or growth factor support within 28 days.
25. Concurrent use of any systemic anticancer therapy.
26. Concurrent use of the following types of drugs or herbal supplements within 21 days prior to randomization or for at least 5 half-lives (whichever is longer):
(a) Potent and intermediate inducers/inhibitors of cytochrome P450 3A4 (CYP3A4)
(b) Sensitive cytochrome P450 2B6 (CYP2B6) receptors
(c) Treatment-index narrowed cytochrome P450 2C9 (CYP2C9) and/or cytochrome P450 2C19 (CYP2C19) receptors, such as warfarin (and other coumarin-derived vitamin K antagonist anticoagulants) and phenytoin.
The above includes, but is not limited to:
27. Use of medications known to prolong the QT interval and with a known risk of multiform ventricular arrhythmias (torsades de pointes, TdP).
28. Systemic use of atropine.
29. The following exclusion criteria apply to the treatment of early-stage breast cancer:
(a) Disease progression within ≤ 84 days after the last dose of pre-adjuvant or adjuvant chemotherapy
(b) Disease progression within ≤ 1 year (365 days) after treatment with a poly(adenosine diphosphate-ribose) polymerase inhibitor (PARPi) and/or platinum-based drugs for early-stage breast cancer
(c) Disease progression within ≤ 1 year (365 days) after the last dose of a cyclin-dependent kinase inhibitor 4/6 (CDK4/6i) under adjuvant therapy conditions
(d) Disease progression within ≤ 1 year (365 days) after the last dose of an oral selective estrogen receptor degrader (including camizestrant).
Other exclusion criteria:
30. Concurrent enrollment in another clinical trial (unless that trial is non-invasive, or you are in the follow-up period of an invasive trial).
31. You are known to have a hypersensitivity to saruparib (AZD5305), any investigational drug in the trial, or any excipients of these drugs.
32. Participation in the planning and/or execution of this trial (applicable to AstraZeneca employees and/or trial center personnel).
33. You should not participate in the trial if the trial administrator determines that you are unlikely to comply with the trial procedures, limitations, and requirements.
34. You have previously been randomly assigned to this trial.
35. Applicable only to women who are currently pregnant (confirmed by a positive pregnancy test) or breastfeeding, or planning to conceive.
Note: If your hepatitis B virus, hepatitis C virus, human immunodeficiency virus, or tuberculosis (TB) test results are positive (including false positives), the hospital will report to the relevant authorities in accordance with the law.
The Estimated Number of Participants
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Taiwan
6 participants
-
Global
500 participants
