Fluzoparib + Bevacizumab vs Olaparib + Bevacizumab for Maintenance Therapy in HRD-Positive Advanced Ovarian Cancer
A Multicenter, Randomized, Open-Label Exploratory Study of Fluzoparib Plus Bevacizumab Versus Olaparib Plus Bevacizumab for Maintenance Therapy After First-Line Platinum-Based Chemotherapy in Patients With HRD-Positive Advanced Ovarian Cancer
The PAOLA-1 trial demonstrated that for HRD-positive patients who received first-line chemotherapy combined with bevacizumab, sequential maintenance therapy with olaparib plus bevacizumab yielded a progression-free survival (PFS) of up to 46.8 months, with an olaparib-related treatment discontinuation rate of approximately 20%.
The combination of olaparib and bevacizumab has been recommended by multiple clinical guidelines as the first-line maintenance regimen for HRD-positive patients treated with first-line chemotherapy plus bevacizumab. This regimen has obtained approved indications and been covered by national medical insurance. In clinical practice, around 30% of patients receiving chemotherapy plus bevacizumab adopt olaparib combined with bevacizumab for first-line maintenance treatment.
Fluzoparib has been approved in China for first-line maintenance therapy in the overall patient population. The treatment discontinuation rate of fluzoparib plus apatinib is merely about 2%. However, there is currently no available data regarding fluzoparib combined with bevacizumab in the HRD-positive population, and the clinical value of this regimen remains to be further explored.
This study aims to generate efficacy and safety data for olaparib plus bevacizumab versus fluzoparib plus bevacizumab in HRD-positive patients who have undergone first-line chemotherapy combined with bevacizumab, so as to provide objective evidence for clinical medication decisions.
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ2
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- The participant voluntarily agrees to take part in the study, signs the informed consent form, demonstrates good treatment compliance, and is willing to complete scheduled follow-up.
- Female participants aged ≥ 18 years (age calculated on the date of signing the informed consent form).
Newly pathologically diagnosed high-grade (or moderately/poorly differentiated) serous ovarian carcinoma, fallopian tube carcinoma or primary peritoneal carcinoma; or grade II and higher ovarian endometrioid adenocarcinoma.
For mixed tumors: The proportion of high-grade serous component or grade II+ endometrioid component must exceed 50%.
- Disease staged as Stage III or Stage IV per the 2018 FIGO staging system.
- Confirmed HRD (Homologous Recombination Deficiency)-positive status via laboratory testing.
- The participant has received 6 to 9 cycles of platinum-based chemotherapy. For participants who cannot tolerate chemotherapy for documented reasons, a minimum of 4 cycles of platinum-based chemotherapy is required.Prior to randomization, participants must have received bevacizumab combined with platinum-based chemotherapy for at least the final 3 cycles, with a minimum of 3 cycles of bevacizumab administration.For participants undergoing interval debulking surgery (IDS), a minimum of 2 cycles of bevacizumab combined with the final 3 cycles of platinum-based chemotherapy is acceptable.
- Prior to randomization, participants must have No Evidence of Disease (NED), or be assessed as having achieved Complete Response (CR) or Partial Response (PR) after first-line platinum-based chemotherapy, and maintain this status until initiation of study treatment. Randomization and study drug administration must be completed within 8 weeks after the last dose of chemotherapy.
- ECOG Performance Status (ECOG-PS) score: 0 or 1.
- Major organ function meets the following requirements. Use of any blood products or hematopoietic growth factors is prohibited within 14 days prior to randomization:
Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L Platelet count ≥ 90 × 10⁹/L Hemoglobin ≥ 9 g/dL Serum albumin ≥ 3 g/dL Total bilirubin ≤ 1.5 × ULN Alanine Transaminase (ALT) and Aspartate Transaminase (AST) ≤ 2.5 × ULN Serum creatinine ≤ 1.5 × ULN 10、For women of childbearing potential: A negative serum pregnancy test result must be obtained within 72 hours prior to randomization. Participants must agree to use one medically approved contraceptive method throughout the study treatment period and for 6 months after the last dose of study drug. Participants must not be breastfeeding.
Exclusion Criteria:
History of other untreated malignant tumors within the past 5 years, or concurrent untreated malignant tumors.
Exceptions: cured thyroid carcinoma, cutaneous basal cell carcinoma, cervical carcinoma in situ, and breast cancer with no recurrence for more than 3 years after radical resection.
- Presence of untreated central nervous system (CNS) metastases. Exception: Participants who have received definitive systemic or radical treatment (radiotherapy or surgery) for brain or meningeal metastases, with radiologically confirmed stable disease for at least 1 month, who have discontinued systemic glucocorticoid therapy (prednisone > 10 mg/day or equivalent glucocorticoids) for more than 2 weeks and have no associated clinical symptoms are eligible.
- Prior exposure to any PARP inhibitors, including but not limited to olaparib, niraparib, rucaparib, pamiparib and fluzoparib.
- Inability to swallow oral tablets normally, or presence of gastrointestinal dysfunction that may interfere with drug absorption, as judged by the investigator.
- History of intestinal obstruction or gastrointestinal perforation within the past 3 months.
- Symptomatic malignant ascites or pleural effusion requiring paracentesis or drainage; or history of ascites/pleural effusion drainage within 3 months prior to randomization.
- Uncontrolled cardiac symptoms or diseases, including:
(1) Heart failure with NYHA Functional Class ≥ 2; (2) Unstable angina pectoris; (3) Myocardial infarction within the past 1 year; (4) Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention; (5) QTc interval > 470 ms. 8、Coagulopathy defined as International Normalized Ratio (INR) > 1.5 or Prothrombin Time (PT) > ULN + 4 seconds; presence of bleeding diathesis, or receipt of thrombolytic or systemic anticoagulant therapy.
Exception: Prophylactic anticoagulation with low-dose low-molecular-weight heparin or oral aspirin is allowed during the study.
9、Clinically significant bleeding events or definite bleeding diathesis within 3 months prior to randomization (e.g., gastrointestinal hemorrhage, hemorrhagic gastric ulcer, vasculitis).
10、If the baseline fecal occult blood test is positive, repeat testing is permitted. If the repeat test remains positive, clinical evaluation is required, and gastroscopy shall be performed if necessary.
11、Presence of active ulcers, unhealed wounds or fractures. Uncontrolled hypertension despite standard antihypertensive therapy (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg).
12、Any bleeding event graded ≥ Grade 2 per CTCAE v6.0 within 4 weeks prior to randomization.
13、Active infection, or unexplained fever > 38.5 °C during the screening period or prior to randomization.
14、Congenital or acquired immunodeficiency (e.g., HIV infection), or active viral hepatitis.
15、Prior radiotherapy, chemotherapy, hormonal therapy or molecular targeted therapy completed less than 4 weeks before study drug administration (less than 5 drug half-lives for oral molecular targeted agents). Adverse events from previous anti-tumor therapies have not recovered to Grade ≤ 1 per CTCAE v6.0 (alopecia is excluded).
16、History of arterial or venous thromboembolic events within 6 months prior to randomization, including cerebrovascular accident (transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, pulmonary embolism, etc.
17、Hereditary or acquired bleeding disorders or coagulation dysfunction (e.g., hemophilia, thrombocytopenia).
18、Plan to receive other systemic anti-tumor therapy during the study period. 19、Any other medical conditions or circumstances that may lead to premature termination of the study, as judged by the investigator.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的:fluzoparib + bevacizumab
Fluzoparib Capsules: Administered orally at a dose of 3 capsules (150 mg) twice daily for a total duration of 2 consecutive years. Morning and evening dosing is allowed, and the drug may be taken with or without food; it is recommended to take each dose within 0.5 hours after breakfast and dinner, with continuous administration throughout the treatment period. Bevacizumab Injection is administered via intravenous infusion at a dose of 15 mg/kg once every 3 weeks. The treatment cycle is repeated every 3 weeks, and administration is continued until disease progression or intolerable toxicity develops, with a maximum total treatment duration of 15 months. |
Fluzoparib Capsules: Administered orally at a dose of 3 capsules (150 mg) twice daily for a total duration of 2 consecutive years. Morning and evening dosing is allowed, and the drug may be taken with or without food; it is recommended to take each dose within 0.5 hours after breakfast and dinner, with continuous administration throughout the treatment period. Bevacizumab Injection is administered via intravenous infusion at a dose of 15 mg/kg once every 3 weeks. The treatment cycle is repeated every 3 weeks, and administration is continued until disease progression or intolerable toxicity develops, with a maximum total treatment duration of 15 months. |
|
実験的:olaparib plus bevacizumab
Administered orally at a dose of 2 tablets (300 mg) twice daily for a total duration of 2 consecutive years. It is recommended to take the drug at fixed times in the morning and evening on an empty stomach (either 1 hour before a meal or 2 hours after a meal), with continuous administration throughout the treatment period. Bevacizumab Injection is administered via intravenous infusion at a dose of 15 mg/kg once every 3 weeks. The treatment cycle is repeated every 3 weeks, and administration is continued until disease progression or intolerable toxicity develops, with a maximum total treatment duration of 15 months. |
Olaparib Tablets: Administered orally at a dose of 2 tablets (300 mg) twice daily for a total duration of 2 consecutive years. It is recommended to take the drug at fixed times in the morning and evening on an empty stomach (either 1 hour before a meal or 2 hours after a meal), with continuous administration throughout the treatment period. Bevacizumab Injection is administered via intravenous infusion at a dose of 15 mg/kg once every 3 weeks. The treatment cycle is repeated every 3 weeks, and administration is continued until disease progression or intolerable toxicity develops, with a maximum total treatment duration of 15 months. |
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
12-month Progression-Free Survival (PFS) Rate
時間枠:From date of randomization up to 12 months post-randomization for rate assessment; overall study assessment is conducted up to 96 months.
|
The proportion of participants who remain free of disease progression (as per RECIST v1.1) or death from any cause at 12 months after randomization.
|
From date of randomization up to 12 months post-randomization for rate assessment; overall study assessment is conducted up to 96 months.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
無増悪生存(PFS)
時間枠:ランダム化の日付から、最初に文書化された進行または原因からの死亡日までのいずれか最初のいずれか、96か月まで評価されたいずれか
|
ランダム化から疾患の進行の発生まで(Recist v1.1による)またはいずれか最初のいずれかの原因による死亡までの時間。
|
ランダム化の日付から、最初に文書化された進行または原因からの死亡日までのいずれか最初のいずれか、96か月まで評価されたいずれか
|
|
全生存(OS)
時間枠:ランダム化の日付から、あらゆる原因による死亡日まで、96か月まで評価されました
|
あらゆる原因によるランダム化から死までの時間。
|
ランダム化の日付から、あらゆる原因による死亡日まで、96か月まで評価されました
|
協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- MA-OC-II-017
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
卵巣がんの臨床試験
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Novartis Pharmaceuticals終了しましたメラノーマ | 高度なEGFR変異体非小さな細胞肺cancer(NSCLC) | KRAS G12変異NSCLC | 食道扁平上皮がん(SCC) | ヘッド/ネックSCC | 進行した胃腸間質腫瘍(GIST) | 進行したNRAS/BRAFT WT皮膚黒色腫アメリカ, 台湾, オランダ, カナダ, スペイン, シンガポール, イタリア, 日本, 韓国
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Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); Highlight Therapeutics積極的、募集していない平滑筋肉腫 | 悪性末梢神経鞘腫瘍 | 滑膜肉腫 | 未分化多形肉腫 | 骨の未分化高悪性度多形肉腫 | 粘液線維肉腫 | II期の体幹および四肢の軟部肉腫 AJCC v8 | III期の体幹および四肢の軟部肉腫 AJCC v8 | IIIA 期の体幹および四肢の軟部肉腫 AJCC v8 | IIIB 期の体幹および四肢の軟部肉腫 AJCC v8 | 切除可能な軟部肉腫 | 多形性横紋筋肉腫 | 切除可能な脱分化型脂肪肉腫 | 切除可能な未分化多形肉腫 | 軟部組織線維肉腫 | 紡錘細胞肉腫 | ステージ I 後腹膜肉腫 AJCC (American Joint Committee on Cancer) v8 | 体幹および四肢の I 期軟部肉腫 AJCC v8 | ステージ... およびその他の条件アメリカ
Fluzoparib+Bevacizumabの臨床試験
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Jinhua ZhouJiangsu Hengrui Pharmaceutical Co., Ltd.まだ募集していません
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Cancer Institute and Hospital, Chinese Academy...まだ募集していません転移性子宮頸がん | 再発子宮頸がん
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Cancer Institute and Hospital, Chinese Academy...まだ募集していませんSCLC、進展期
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Shanghai Pudong HospitalShanghai Junshi Bioscience Co., Ltd.まだ募集していません
-
Cancer Institute and Hospital, Chinese Academy...Beijing Jishuitan Hospital完了
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Weill Medical College of Cornell University終了しました多形性膠芽腫 | 退形成性星細胞腫 | びまん性内因性橋グリオーマ | 脳幹グリオーマ | 毛包粘液性星細胞腫 | 脳幹の神経膠腫 | 脳の線維性星細胞腫 | 混合乏突起膠腫-星細胞腫アメリカ