- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT07647653
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.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: 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. |
|
Experimentální: 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. |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
12-month Progression-Free Survival (PFS) Rate
Časové okno: 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.
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Přežití bez progrese (PFS)
Časové okno: Od data randomizace do data prvního zdokumentovaného postupu nebo datu úmrtí z jakékoli příčiny, podle toho, co přišlo na prvním místě, bylo posouzeno až 96 měsíců
|
Čas od randomizace po výskyt progrese onemocnění (podle RECIST v1.1) nebo smrt z jakékoli příčiny, podle toho, co nastane jako první.
|
Od data randomizace do data prvního zdokumentovaného postupu nebo datu úmrtí z jakékoli příčiny, podle toho, co přišlo na prvním místě, bylo posouzeno až 96 měsíců
|
|
Celkové přežití (OS)
Časové okno: Od data randomizace do data úmrtí z jakékoli věci, posouzeno až 96 měsíců
|
Čas od randomizace k smrti z důvodu jakékoli příčiny.
|
Od data randomizace do data úmrtí z jakékoli věci, posouzeno až 96 měsíců
|
Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Urogenitální onemocnění
- Onemocnění genitálií
- Onemocnění endokrinního systému
- Urogenitální novotvary
- Novotvary podle místa
- Novotvary
- Ženské urogenitální onemocnění
- Ženské urogenitální onemocnění a těhotenské komplikace
- Onemocnění pohlavních orgánů, ženy
- Novotvary endokrinních žláz
- Onemocnění vaječníků
- Adnexální onemocnění
- Genitální novotvary, ženy
- Gonadální poruchy
- Novotvary vaječníků
Další identifikační čísla studie
- MA-OC-II-017
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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