PDS Versus NACT-IDS in AI-Selected Advanced Epithelial Ovarian Cancer
Artificial Intelligence -Assisted Randomized Phase II/III Trial of Primary Debulking Surgery Versus Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer
This multicenter, open-label, randomized phase II/III trial will compare primary debulking surgery (PDS) with neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) in patients with newly diagnosed stage IIIC or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer who are recommended for PDS by the MERITS clinical decision tool and are clinically eligible for either treatment strategy.
Descripción general del estudio
Estado
Descripción detallada
The optimal timing of cytoreductive surgery in advanced epithelial ovarian cancer remains uncertain. Earlier randomized trials did not clearly identify which patients benefit from PDS rather than NACT-IDS. Using data from 489 participants in the SUNNY trial, the Multi-Endpoint RMST Ensemble for Individualized Treatment Selection (MERITS) model was developed and internally evaluated in the previous SUNNY-AI trial (NCT06839157). The model uses seven pretreatment clinical variable groups: BRCA status, TNM stage, Eastern Cooperative Oncology Group performance status, histologic type, tumor burden, presence of omental metastasis, and age (≤65 vs >65 years). In internal cross-validation, MERITS recommended PDS for 78.1% of patients and achieved a concordance index of 0.63. The current study will prospectively evaluate the clinical utility of feature-based selection and determine whether PDS improves overall survival in the selected population.
All participants must be recommended for PDS by MERITS and judged clinically suitable for both PDS and NACT-IDS. A 20-participant randomized pioneer study will first assess feasibility and early safety. Formal phase II enrollment may begin if major protocol deviations are observed in no more than 4 of 20 participants, 30-day grade ≥3 postoperative complications in no more than 6, 30-day postoperative deaths in no more than 1, at least 18 undergo the planned debulking procedure, and all operated participants have ascertainable 30-day safety outcomes.
The randomized phase II will enroll 100 participants. Phase II will be assessed after the 100th participant has completed 18 months of follow-up and surgical safety data have been verified. The phase II decision is exploratory and does not establish confirmatory noninferiority. The phase III will enroll 414 participants. The final phase III analysis will be performed after at least 247 deaths and at least 60 months of follow-up for the last phase III participant. Overall survival will be compared using a stratified log-rank test, with a stratified Cox model estimating the hazard ratio for PDS versus NACT-IDS and its two-sided 95% confidence interval. Stratification factors are TNM stage, cPCI tumor burden, and BRCA status. PDS will be considered superior only if the estimated hazard ratio is <1 and the two-sided stratified log-rank P value is <0.05.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 3
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Yulian Chen, MD
- Número de teléfono: 86 21 64041990
- Correo electrónico: emma_serendipity@163.com
Ubicaciones de estudio
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Porcelana
- Zhongshan Hospital Fudan University
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Contacto:
- Rongyu Zang, MD, PhD
- Número de teléfono: 02164041990
- Correo electrónico: zang.rongyu@zs-hospital.sh.cn
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Contacto:
- Libing Xiang, MD, PhD
- Número de teléfono: 02164041990
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Zhejiang
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Hangzhou, Zhejiang, Porcelana
- Zhejiang cancer hospital
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Contacto:
- Jianqing Zhu, MD
- Número de teléfono: 86 571 8822222
- Correo electrónico: zjq-hz@126.com
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Female, aged ≥18 and <80 years.
- Newly diagnosed, pathologically confirmed stage IIIC or IV primary epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma. Diagnostic surgery, core-needle biopsy, or a pleural/ascitic fluid cell block may be used for confirmation as specified in the protocol.
- PET-CT based TNM clinical stage and cPCI tumor burden determined by multidisciplinary assessment.
- Eastern Cooperative Oncology Group performance status 0-2.
- Frailty index <0.15.
- Known BRCA1/2 status.
- MERITS recommendation for PDS and clinical eligibility for both randomized treatment strategies.
- Adequate bone marrow, renal, hepatic, and nutritional function to undergo chemotherapy and surgery: white blood cell count >3,000/µL; absolute neutrophil count ≥1,500/µL; platelets ≥100,000/µL; hemoglobin ≥9 g/dL; serum creatinine <1.25 × upper limit of normal or creatinine clearance ≥60 mL/min; total bilirubin <1.25 × upper limit of normal; ALT and AST <2.5 × upper limit of normal; and serum albumin >3.5 g/dL.
- Ability and willingness to comply with protocol treatment and scheduled follow-up.
- Written informed consent.
Exclusion Criteria:
- Low-grade ovarian carcinoma, mucinous ovarian carcinoma, or clear cell carcinoma.
- Non-epithelial ovarian malignancy or borderline ovarian tumor.
- Prior neoadjuvant chemotherapy, targeted therapy, immunotherapy, or other systemic anticancer therapy for the current disease.
- Concurrent or uncontrolled malignancy diagnosed within the previous 5 years.
- Severe systemic disease precluding surgery, including poorly controlled diabetes or hypertension, chronic obstructive pulmonary disease, implanted cardiac pacemaker with clinically relevant comorbidity, moderately reduced cardiac ejection fraction, end-stage renal disease, myocardial infarction, cerebrovascular accident, uncontrolled infection, coagulation disorder, or another condition judged to make surgery or chemotherapy unsafe.
- Inability to complete the planned treatment course or follow-up.
- Religious, psychological, or other circumstances that could interfere with informed consent, protocol adherence, or follow-up.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Primary Debulking Surgery
Maximal-effort cytoreductive surgery will be completed within 3 weeks after pathologic diagnosis, followed by 6 cycles of first-line chemotherapy. The interval from surgery to the first postoperative chemotherapy cycle should not exceed 8 weeks unless medically necessary. |
Upfront cytoreductive surgery with a maximum cytoreduction, then followed by 6 cycles of Paclitaxel 175mg/m2 or Docetaxel 60-75 mg/m2 plus Carboplatin AUC (area under the curve) 5 Paclitaxel 175mg/m2 or Docetaxel 60-75 mg/m2 plus Carboplatin AUC (area under the curve) 5 |
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Comparador activo: Neoadjuvant Chemotherapy Followed by Interval Debulking Surgery
Participants will receive 3 cycles of neoadjuvant chemotherapy, undergo interval debulking surgery with maximal-effort cytoreduction, and then receive 3 additional cycles of chemotherapy. The interval from surgery to the first postoperative chemotherapy cycle should not exceed 8 weeks unless medically necessary. |
Paclitaxel 175mg/m2 or Docetaxel 60-75 mg/m2 plus Carboplatin AUC (area under the curve) 5 3 cycles of Paclitaxel 175mg/m2 or Docetaxel 60-75 mg/m2 plus Carboplatin AUC (area under the curve) 5, Interval debulking surgery with a maximal cytoreduction of complete gross resection, then followed by another 3 cycles of chemotherapy |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Overall survival
Periodo de tiempo: 60 months since randomization
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Time from randomization to death from any cause; participants alive will be censored at the last date known alive. |
60 months since randomization
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Progression-free survival
Periodo de tiempo: 60 months since randomization
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Time from randomization to first disease progression or death from any cause, whichever occurs first. |
60 months since randomization
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Postoperative complications within 30 days after surgery
Periodo de tiempo: Through 30 days after the planned debulking procedure
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The surgical complications will be evaluated at 30-day after upfront cytoreductive surgery or interval debulking surgery, graded using CTCAE version 5.03 |
Through 30 days after the planned debulking procedure
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Quality of life assessments
Periodo de tiempo: At baseline, 6 months, 12 months, and 5 years after randomization.
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Quality of life measured with EORTC QLQ-C30 |
At baseline, 6 months, 12 months, and 5 years after randomization.
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Pattern of first relapse
Periodo de tiempo: 60 months since randomization
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The number and sites of the first relapse, including pelvic, abdominal, retroperitoneal lymph nodes, distant metastases and ascites will be compared between the two groups. |
60 months since randomization
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The rate of 3-year progression-free survival
Periodo de tiempo: 36 months since randomization
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The rate of the patients without progression or recurrence or death at 3 years. |
36 months since randomization
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The rate of 5-year progression-free survival
Periodo de tiempo: 60 months since randomization
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The rate of the patients without progression or recurrence or death at 5 years. |
60 months since randomization
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Enfermedades Genitales
- Enfermedades del sistema endocrino
- Neoplasias urogenitales
- Neoplasias por sitio
- Neoplasias
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Neoplasias por tipo histológico
- Enfermedades Genitales Femeninas
- Neoplasias de glándulas endocrinas
- Neoplasias Glandulares y Epiteliales
- Enfermedades Ováricas
- Enfermedades anexiales
- Neoplasias Genitales Femeninas
- Trastornos gonadales
- Carcinoma
- Enfermedades de las trompas de Falopio
- Neoplasias Ováricas
- Carcinoma Epitelial De Ovario
- Neoplasias de las trompas de Falopio
- Químicos inorgánicos
- Compuestos de platino
Otros números de identificación del estudio
- OV-AI
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
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