計劃書編號WO43571
NCT Number(ClinicalTrials.gov Identfier)NCT05296798
試驗執行中
2022-06-01 - 2032-12-31
Phase III
召募中5
ICD-10C50.011
女性右側乳房乳頭及乳暈之惡性腫瘤
ICD-10C50.012
女性左側乳房乳頭及乳暈之惡性腫瘤
ICD-10C50.019
女性未明示側性乳房乳頭及乳暈之惡性腫瘤
ICD-10Z51.12
來院接受抗腫瘤免疫療法
ICD-9174.0
女性乳房乳頭及乳暈之惡性腫瘤
一項第三期、隨機分配、開放性試驗，評估在接受 PHESGO+TAXANE 類藥物誘導治療後，GIREDESTRANT 併用 PHESGO 相較於 PHESGO，用於先前未經治療的 HER2 陽性、雌激素受體陽性局部晚期或轉移性乳癌病患的療效及安全性
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試驗申請者
羅氏大藥廠股份有限公司
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試驗委託 / 贊助單位名稱
羅氏大藥廠股份有限公司
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臨床試驗規模
多國多中心
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更新日期
2026/02/01
試驗主持人及試驗醫院
實際收案人數
0 召募中
實際收案人數
0 召募中
適應症
先前未經治療的 HER2 陽性、雌激素受體陽性局部晚期或轉移性乳癌
試驗目的
本試驗目的為，針對先前未經治療局部晚期無法切除或轉移性雌激素受體(ER)陽性、第 2 型人類表皮生長因子受體(HER2)陽性乳癌(BC)受試者，評估在接受 4 至 6 個週期 Phesgo+taxane 類藥物誘導治療(即依標準照護接受 docetaxel 或 paclitaxel)後，使用 giredestrant，一種新型口服選擇性雌激素受體降解劑(SERD)併用 Phesgo™ (pertuzumab、trastuzumab 和 HuPH20，皮下注射用途)的療效及安全性。儘管已在早期診斷和治癒性多重治療方式有所進展，但仍有一些病患可能會出現轉移性復發或出現「新的」轉移性乳癌(MBC)。持續需要具有更好效益風險概況的治療來延長 ER 陽性、HER2 陽性晚期乳癌(ABC)病患的無惡化存活期(PFS)及其他存活期試驗指標。
藥品名稱
膠囊劑
主成份
Giredestrant
pertuzumab
trastuzumab
rHuPH20
pertuzumab
trastuzumab
rHuPH20
pertuzumab
trastuzumab
rHuPH20
pertuzumab
trastuzumab
rHuPH20
劑型
Capsule
Solution for injection
Solution for injection
Solution for injection
Solution for injection
劑量
30 mg/capsule
80 mg/mL
60 mg/mL
2,000 U/mL
60 mg/mL
60 mg/mL
2,000 U/mL
80 mg/mL
60 mg/mL
2,000 U/mL
60 mg/mL
60 mg/mL
2,000 U/mL
評估指標
PFS，定義為自隨機分配至第一次出現疾病惡化或因任何原因死亡(以先發生者為準)的時間，由試驗主持人根據實體腫瘤反應評估標準第 1.1 版(RECIST v1.1)判定
主要納入條件
•已簽署受試者同意書
•簽署受試者同意書時年齡≥ 18歲(在台灣將僅納入≥ 20歲的病患)
•由試驗主持人判斷能夠遵從本試驗之試驗計畫書
•經組織學或細胞學證實並記錄患有無法進行根治性切除的轉移性或局部晚期疾病之乳腺癌。
–試驗納入前由中央實驗室確認為HER2陽性晚期乳癌(ABC)。HER2陽性狀態將依據主要或轉移性病灶判定，定義為免疫組織化學分析法(IHC)達到3+及/或原位雜合反應(ISH)測得HER2放大陽性，且HER2基因拷貝數對17號染色體拷貝數的訊號數比值≥ 2。只要至少一種HER2檢測(IHC或ISH)得到陽性結果，參與者即可符合資格
試驗納入前必須提交一份具有代表性的福馬林固定、石蠟包埋(FFPE)腫瘤檢體之石蠟組織塊(建議)或至少20份包含未染色、新切、符合第8.7節所述條件之連續切片。特殊情況下，只要符合其他資格要求，則可接受1119份切片；但是，強烈建議至少20份切片。對於中國，符合資格要求的切片數量將根據中國人類遺傳資源管理辦公室(HGRAC)的規範
–根據美國臨床腫瘤學會/美國病理學會(ASCO/CAP)的規範，腫瘤有ER陽性之紀錄，陽性之定義為當地依照用於確定HER2陽性的同一病灶(建議)，評估有≥ 1%的腫瘤細胞染色為ER陽性
•根據RECIST第1.1版，評估至少有一個可測量的病灶和/或不可測量的疾病
–試驗結束後接受誘導治療的參與者之備註：基期腫瘤評估必須符合第8.1.1.1節所列之條件
•自完成輔助性或前導性全身性非荷爾蒙治療到疾病復發的無疾病間隔期≥ 6個月
•美國東岸癌症臨床研究合作組織(ECOG)體能狀態為0或1
•以心臟超音波(ECHO)或多頻道心室功能攝影掃描(MUGA)所測量的左心室射出率(LVEF)至少為50%
•良好的血液及末端器官功能，以下列於納入前7天內取得的實驗室檢查結果定義：
–未補充顆粒性白血球聚落刺激因子時，嗜中性白血球絕對計數(ANC) ≥ 1.5 x 109/L (1500 cells/μL)，但有一項例外：
患有良性家族性嗜中性白血球缺乏症的參與者：ANC ≥ 1.3 x 109/L (1300/μL)
–血小板計數≥ 100,000 cells/L
–血紅素≥ 9.0 g/dL
參與者可接受紅血球(RBC)輸血以達到此濃度
–根據機構規範計算，估算的肌酸酐清除率≥ 30 mL/min
–國際標準化比值(INR)和活化部份凝血活酶時間(aPTT) ≤ 1.5倍正常值上限(ULN) (接受抗凝血治療的參與者除外)
對於接受warfarin之參與者，穩定的INR需介於2到3之間。
對於接受肝素之參與者，PTT (或aPTT)需介於1.5到2.5 ULN之間。
若因為人工心臟瓣膜而需要抗凝血劑療法，則允許穩定INR介於2.5到3.5之間。
–血清天門冬胺酸轉胺酶(AST)和丙胺酸轉胺酶(ALT) ≤ 3倍ULN (有肝臟轉移紀錄的參與者：AST和ALT ≤ 5倍ULN)
–血清總膽紅素(TBILI) ≤ 1.5倍ULN，但患有吉伯特氏症候群的病患除外(≤ 3倍ULN)，其直接膽紅素應在正常範圍內
–血清白蛋白≥ 25 g/L (2.5 g/dL)
•具有生育能力的女性：參與者必須同意持續禁慾(不進行異性間性行為)或使用避孕方法，且同意不得捐贈卵子，定義如下：
女性必須在治療期間及最後一劑Phesgo(賀雙妥皮下注射劑)後7個月內維持禁慾，或使用每年失敗率＜ 1%的非荷爾蒙避孕方法。若女性已有月經來潮且未達停經狀態(連續≥ 12個月沒有月經且未發現其他非更年期造成停經的原因)，並且沒有因為手術(即移除卵巢、輸卵管及/或子宮)，或其他由試驗主持人判定的原因(例如：苗勒管發育不全)而導致永久不孕，即認定為具有生育能力。具有生育能力的定義可以依據當地規範或法規來修正。
每年失敗率＜ 1%的非荷爾蒙避孕方法範例包括雙側輸卵管結紮、男性絕育及含銅子宮內避孕器。
應依據臨床試驗期間以及個人的偏好與一般生活型態評估禁慾的可靠性。週期禁慾法(例如：月曆、排卵、基礎體溫法或排卵後期法)和性交中斷法均不是適當的避孕方法。若當地規範或法規規定，將於當地受試者同意書內說明當地認可且適當的避孕措施以及有關禁慾可靠性的資訊。
•針對男性：參與者同意持續禁慾(不進行異性間性行為)或使用保險套，且同意不捐贈精子，定義如下：
伴侶為具生育能力女性或懷孕女性時，男性必須在治療期間及最後一劑Phesgo(賀雙妥皮下注射劑)後7個月內持續禁慾或使用保險套，以避免胚胎暴露在藥物中。男性在此相同期間內不得捐贈精子。
應依據臨床試驗期間以及個人的偏好與一般生活型態評估禁慾的可靠性。週期禁慾法(例如：月曆、排卵、基礎體溫法或排卵後期法)和性交中斷法均不是適當的避免藥物暴露的方法。若當地規範或法規規定，將於當地受試者同意書內說明有關禁慾可靠性的資訊。
維持期條件
參與者必須符合以下所有條件，方符合資格隨機分配至本試驗的維持期：
•完成至少四個週期的誘導治療，其定義為
–4次Phesgo(賀雙妥皮下注射劑)注射+ 4次docetaxel輸注
或是
–4次Phesgo(賀雙妥皮下注射劑)注射+ 12次paclitaxel輸注
註：若參與者在納入前已接受一個或兩個週期的誘導治療，這些週期將計入維持期資格所需的週期數(例如，若參與者在納入前接受一個週期的Phesgo(賀雙妥皮下注射劑) [或trastuzumab SC與pertuzumab IV或PH IV] + docetaxel，進入維持期前至少需要接受3個週期的Phesgo(賀雙妥皮下注射劑) + docetaxel)
•根據RECIST第1.1版，在誘導治療期間的最後一次腫瘤評估時達到SD狀態的最低值[或患有不可測量疾病的參與者為非CR/非PD] (即未出現PD)
•誘導治療期間的最後一次評估時，左心室射出率(LVEF) ≥ 50%
•簽署受試者同意書時年齡≥ 18歲(在台灣將僅納入≥ 20歲的病患)
•由試驗主持人判斷能夠遵從本試驗之試驗計畫書
•經組織學或細胞學證實並記錄患有無法進行根治性切除的轉移性或局部晚期疾病之乳腺癌。
–試驗納入前由中央實驗室確認為HER2陽性晚期乳癌(ABC)。HER2陽性狀態將依據主要或轉移性病灶判定，定義為免疫組織化學分析法(IHC)達到3+及/或原位雜合反應(ISH)測得HER2放大陽性，且HER2基因拷貝數對17號染色體拷貝數的訊號數比值≥ 2。只要至少一種HER2檢測(IHC或ISH)得到陽性結果，參與者即可符合資格
試驗納入前必須提交一份具有代表性的福馬林固定、石蠟包埋(FFPE)腫瘤檢體之石蠟組織塊(建議)或至少20份包含未染色、新切、符合第8.7節所述條件之連續切片。特殊情況下，只要符合其他資格要求，則可接受1119份切片；但是，強烈建議至少20份切片。對於中國，符合資格要求的切片數量將根據中國人類遺傳資源管理辦公室(HGRAC)的規範
–根據美國臨床腫瘤學會/美國病理學會(ASCO/CAP)的規範，腫瘤有ER陽性之紀錄，陽性之定義為當地依照用於確定HER2陽性的同一病灶(建議)，評估有≥ 1%的腫瘤細胞染色為ER陽性
•根據RECIST第1.1版，評估至少有一個可測量的病灶和/或不可測量的疾病
–試驗結束後接受誘導治療的參與者之備註：基期腫瘤評估必須符合第8.1.1.1節所列之條件
•自完成輔助性或前導性全身性非荷爾蒙治療到疾病復發的無疾病間隔期≥ 6個月
•美國東岸癌症臨床研究合作組織(ECOG)體能狀態為0或1
•以心臟超音波(ECHO)或多頻道心室功能攝影掃描(MUGA)所測量的左心室射出率(LVEF)至少為50%
•良好的血液及末端器官功能，以下列於納入前7天內取得的實驗室檢查結果定義：
–未補充顆粒性白血球聚落刺激因子時，嗜中性白血球絕對計數(ANC) ≥ 1.5 x 109/L (1500 cells/μL)，但有一項例外：
患有良性家族性嗜中性白血球缺乏症的參與者：ANC ≥ 1.3 x 109/L (1300/μL)
–血小板計數≥ 100,000 cells/L
–血紅素≥ 9.0 g/dL
參與者可接受紅血球(RBC)輸血以達到此濃度
–根據機構規範計算，估算的肌酸酐清除率≥ 30 mL/min
–國際標準化比值(INR)和活化部份凝血活酶時間(aPTT) ≤ 1.5倍正常值上限(ULN) (接受抗凝血治療的參與者除外)
對於接受warfarin之參與者，穩定的INR需介於2到3之間。
對於接受肝素之參與者，PTT (或aPTT)需介於1.5到2.5 ULN之間。
若因為人工心臟瓣膜而需要抗凝血劑療法，則允許穩定INR介於2.5到3.5之間。
–血清天門冬胺酸轉胺酶(AST)和丙胺酸轉胺酶(ALT) ≤ 3倍ULN (有肝臟轉移紀錄的參與者：AST和ALT ≤ 5倍ULN)
–血清總膽紅素(TBILI) ≤ 1.5倍ULN，但患有吉伯特氏症候群的病患除外(≤ 3倍ULN)，其直接膽紅素應在正常範圍內
–血清白蛋白≥ 25 g/L (2.5 g/dL)
•具有生育能力的女性：參與者必須同意持續禁慾(不進行異性間性行為)或使用避孕方法，且同意不得捐贈卵子，定義如下：
女性必須在治療期間及最後一劑Phesgo(賀雙妥皮下注射劑)後7個月內維持禁慾，或使用每年失敗率＜ 1%的非荷爾蒙避孕方法。若女性已有月經來潮且未達停經狀態(連續≥ 12個月沒有月經且未發現其他非更年期造成停經的原因)，並且沒有因為手術(即移除卵巢、輸卵管及/或子宮)，或其他由試驗主持人判定的原因(例如：苗勒管發育不全)而導致永久不孕，即認定為具有生育能力。具有生育能力的定義可以依據當地規範或法規來修正。
每年失敗率＜ 1%的非荷爾蒙避孕方法範例包括雙側輸卵管結紮、男性絕育及含銅子宮內避孕器。
應依據臨床試驗期間以及個人的偏好與一般生活型態評估禁慾的可靠性。週期禁慾法(例如：月曆、排卵、基礎體溫法或排卵後期法)和性交中斷法均不是適當的避孕方法。若當地規範或法規規定，將於當地受試者同意書內說明當地認可且適當的避孕措施以及有關禁慾可靠性的資訊。
•針對男性：參與者同意持續禁慾(不進行異性間性行為)或使用保險套，且同意不捐贈精子，定義如下：
伴侶為具生育能力女性或懷孕女性時，男性必須在治療期間及最後一劑Phesgo(賀雙妥皮下注射劑)後7個月內持續禁慾或使用保險套，以避免胚胎暴露在藥物中。男性在此相同期間內不得捐贈精子。
應依據臨床試驗期間以及個人的偏好與一般生活型態評估禁慾的可靠性。週期禁慾法(例如：月曆、排卵、基礎體溫法或排卵後期法)和性交中斷法均不是適當的避免藥物暴露的方法。若當地規範或法規規定，將於當地受試者同意書內說明有關禁慾可靠性的資訊。
維持期條件
參與者必須符合以下所有條件，方符合資格隨機分配至本試驗的維持期：
•完成至少四個週期的誘導治療，其定義為
–4次Phesgo(賀雙妥皮下注射劑)注射+ 4次docetaxel輸注
或是
–4次Phesgo(賀雙妥皮下注射劑)注射+ 12次paclitaxel輸注
註：若參與者在納入前已接受一個或兩個週期的誘導治療，這些週期將計入維持期資格所需的週期數(例如，若參與者在納入前接受一個週期的Phesgo(賀雙妥皮下注射劑) [或trastuzumab SC與pertuzumab IV或PH IV] + docetaxel，進入維持期前至少需要接受3個週期的Phesgo(賀雙妥皮下注射劑) + docetaxel)
•根據RECIST第1.1版，在誘導治療期間的最後一次腫瘤評估時達到SD狀態的最低值[或患有不可測量疾病的參與者為非CR/非PD] (即未出現PD)
•誘導治療期間的最後一次評估時，左心室射出率(LVEF) ≥ 50%
主要排除條件
Exclusion Criteria:
Previous systemic non-hormonal anti-cancer therapy in the metastatic breast cancer (MBC) or advanced breast cancer (ABC) setting. Note: Up to one line of single-agent endocrine therapy given in the metastatic or locally advanced setting will be allowed.
Prior treatment with a selective estrogen receptor degrader (SERD)
Previous treatment with approved or investigative anti-HER2 agents in any breast cancer treatment setting, except Phesgo (or trastuzumab SC with pertuzumab IV, or pertuzumab and trastuzumab IV), single-agent trastuzumab IV or SC, ado-trastuzumab emtansine, lapatinib, and neratinib in the neoadjuvant or adjuvant setting
Disease progression within 6 months of receiving adjuvant anti-HER2 therapy (such as trastuzumab, with or without pertuzumab [IV, SC, or fixed-dose combination], or ado-trastuzumab emtansine, or neratinib)
Non-resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) Grade 1 or better
History of persistent Grade ≥2 (NCI-CTC, Version 5.0) hematological toxicity resulting from previous adjuvant or neo-adjuvant therapy
History of exposure to the following cumulative doses of anthracyclines; Doxorubicin >360 mg/m2; Liposomal doxorubicin >500 mg/m2; Epirubucin >720 mg/m2; Mitoxantrone >120 mg/m2; Idarubicin >90 mg/m2.
Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease
Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy
Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the final dose of Phesgo (Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of induction therapy).
Treated with investigational therapy within 28 days prior to initiation of induction therapy
Treated with localized palliative radiotherapy within 14 days prior to initiation of induction therapy
Concurrent participation in any other therapeutic clinical trial
Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies
Current chronic daily treatment (continuous for >3 months) with corticosteroids (dose of 10 mg/day methylprednisolone or equivalent)
Poorly controlled hypertension
Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, active liver disease including active viral or other hepatitis virus, autoimmune hepatic disorders, or sclerosing cholangitis, current alcohol abuse, or cirrhosis
Active cardiac disease or history of cardiac dysfunction
Major surgical procedure or significant traumatic injury within 14 days prior to enrollment or anticipation of need for major surgery during induction therapy
Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal surgery
Concurrent, serious, uncontrolled infections, or known infection with HIV with the following exception: Individuals who are HIV positive are eligible provided they are stable on anti-retroviral therapy for ≥4 weeks, have a CD4 count ≥350 cells/uL, and have an undetectable viral load and no history of AIDS-defining opportunistic infections within 12 months prior to enrollment.
Serious COVID-19 infection within 14 days prior to enrollment; however, no screening testing for SARS-CoV-2 is required
Serious infection requiring oral or IV antibiotics within 7 days prior to screening
Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in the study
History of malignancy within 5 years prior to screening with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death
For pre- and perimenopausal women, and men: Known hypersensitivity to luteinizing hormone-releasing hormone agonist (LHRHa); Not willing to undergo and maintain treatment with approved LHRHa therapy for the duration of endocrine therapy that requires gonadal function suppression
Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of giredestrant treatment in Arm B
A documented history of hemorrhagic diathesis, coagulopathy, or thromboembolism, including deep vein thrombosis, unless the condition is adequately treated and under control
Previous systemic non-hormonal anti-cancer therapy in the metastatic breast cancer (MBC) or advanced breast cancer (ABC) setting. Note: Up to one line of single-agent endocrine therapy given in the metastatic or locally advanced setting will be allowed.
Prior treatment with a selective estrogen receptor degrader (SERD)
Previous treatment with approved or investigative anti-HER2 agents in any breast cancer treatment setting, except Phesgo (or trastuzumab SC with pertuzumab IV, or pertuzumab and trastuzumab IV), single-agent trastuzumab IV or SC, ado-trastuzumab emtansine, lapatinib, and neratinib in the neoadjuvant or adjuvant setting
Disease progression within 6 months of receiving adjuvant anti-HER2 therapy (such as trastuzumab, with or without pertuzumab [IV, SC, or fixed-dose combination], or ado-trastuzumab emtansine, or neratinib)
Non-resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) Grade 1 or better
History of persistent Grade ≥2 (NCI-CTC, Version 5.0) hematological toxicity resulting from previous adjuvant or neo-adjuvant therapy
History of exposure to the following cumulative doses of anthracyclines; Doxorubicin >360 mg/m2; Liposomal doxorubicin >500 mg/m2; Epirubucin >720 mg/m2; Mitoxantrone >120 mg/m2; Idarubicin >90 mg/m2.
Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease
Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy
Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the final dose of Phesgo (Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of induction therapy).
Treated with investigational therapy within 28 days prior to initiation of induction therapy
Treated with localized palliative radiotherapy within 14 days prior to initiation of induction therapy
Concurrent participation in any other therapeutic clinical trial
Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies
Current chronic daily treatment (continuous for >3 months) with corticosteroids (dose of 10 mg/day methylprednisolone or equivalent)
Poorly controlled hypertension
Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, active liver disease including active viral or other hepatitis virus, autoimmune hepatic disorders, or sclerosing cholangitis, current alcohol abuse, or cirrhosis
Active cardiac disease or history of cardiac dysfunction
Major surgical procedure or significant traumatic injury within 14 days prior to enrollment or anticipation of need for major surgery during induction therapy
Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal surgery
Concurrent, serious, uncontrolled infections, or known infection with HIV with the following exception: Individuals who are HIV positive are eligible provided they are stable on anti-retroviral therapy for ≥4 weeks, have a CD4 count ≥350 cells/uL, and have an undetectable viral load and no history of AIDS-defining opportunistic infections within 12 months prior to enrollment.
Serious COVID-19 infection within 14 days prior to enrollment; however, no screening testing for SARS-CoV-2 is required
Serious infection requiring oral or IV antibiotics within 7 days prior to screening
Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in the study
History of malignancy within 5 years prior to screening with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death
For pre- and perimenopausal women, and men: Known hypersensitivity to luteinizing hormone-releasing hormone agonist (LHRHa); Not willing to undergo and maintain treatment with approved LHRHa therapy for the duration of endocrine therapy that requires gonadal function suppression
Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of giredestrant treatment in Arm B
A documented history of hemorrhagic diathesis, coagulopathy, or thromboembolism, including deep vein thrombosis, unless the condition is adequately treated and under control
試驗計畫預計收納受試者人數
-
台灣人數
65 人
-
全球人數
922 人
