- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT07667751
An Exploratory Study on the Use of Ipalotinib (Tislelizumab) Combined With Sunitinib and Olaparib for Neoadjuvant Therapy in HRD-positive Advanced Ovarian Cancer
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
For patients with advanced ovarian cancer, tumor debulking surgery is a crucial component of treatment. However, due to poor prognosis and high recurrence rates in advanced cases, treatment poses significant challenges. The primary principle of surgical management for advanced ovarian cancer is to achieve maximal tumor resection. The core objective of surgery is to remove all macroscopically visible tumor tissue to minimize postoperative residual disease. Nevertheless, given the complexity of advanced ovarian cancer and individual patient variability, not all patients are suitable candidates for initial tumor debulking surgery. Neoadjuvant chemotherapy combined with intermediate tumor debulking surgery serves as a therapeutic option for patients who cannot achieve satisfactory tumor reduction or are unable to tolerate surgery, and this approach is currently widely employed in clinical practice.
The traditional neoadjuvant treatment regimen for ovarian cancer involves the platinum-paclitaxel dual-drug combination. However, the complete resection rate with pure neoadjuvant chemotherapy remains below 50%, and approximately half of patients fail to achieve complete tumor removal. These patients face the risk of residual tumors postoperatively, which increases the likelihood of disease recurrence, highlighting a significant unmet clinical need. Improving neoadjuvant treatment strategies for ovarian cancer has become a current research focus. Existing studies demonstrate that combining immune checkpoint inhibitors with neoadjuvant chemotherapy can enhance the pathological complete response (pCR) rate in advanced ovarian cancer patients and induce durable clinical responses, suggesting this approach as a promising therapeutic option; however, further validation is required, and the optimal immunotherapy combination strategy requires further exploration.
Apatinib-tolilimumab (hereinafter referred to as the Ato combination antibody) is the world's first dual-functional combination antibody targeting both PD-1 and CTLA-4, capable of simultaneously inhibiting PD-1-and CTLA-4-mediated signaling pathways to exert synergistic antitumor effects with excellent tolerability. In Phase I clinical studies, the Ato combination antibody demonstrated superior safety and tolerability. Among 518 patients with advanced cancer who had failed conventional treatments, only 8.1% experienced grade 3 or higher immune-related adverse events, highlighting its significant safety advantages. In patients with recurrent or metastatic cervical cancer, the pivotal Phase II registration study of the Ato combination antibody achieved remarkable results: an overall response rate (ORR) of 33.8% in second-line systemic therapy and a median progression-free survival (PFS) of 5.4 months. Based on these data, the Ato combination antibody was approved for marketing in China on September 30,2024, indicated for the treatment of recurrent or metastatic cervical cancer patients who had previously failed platinum-based chemotherapy.
PARP inhibitors and antiangiogenic agents can disrupt tumor growth through distinct mechanisms, with their synergistic effects mutually enhancing each other to achieve a 1+1>2 outcome. Multitarget tyrosine kinase inhibitors (TKIs) can induce remodeling of the immune microenvironment and activate the tumor immune response, not only significantly increasing T-cell infiltration into tumors but also upregulating the expression of the immune checkpoint CTLA-4, ultimately enabling tumor cells to evade T-cell attack through immune evasion. CTLA-4 blockade enhances T-cell antitumor activity and effectively reverses the inhibitory immune microenvironment. Sunitinib is a TKI currently used as standard therapy for clear cell renal cell carcinoma (ccRCC) and gastrointestinal stromal tumors (GIST). Studies suggest that sunitinib may play a role in tumor immune monitoring and participate in PD-L1 regulation.
In patients with previously untreated advanced ovarian cancer, the use of neoadjuvant therapy combining TKIs and PARP inhibitors with epalolide and torvocizumab has a solid scientific basis and warrants further investigation. This study innovatively employed sunitinib combined with olaparib for one cycle to induce an immune microenvironment, followed by addition of an immune checkpoint inhibitor, demonstrating synergistic effects. To further evaluate the efficacy and safety of sunitinib and olaparib combined with epalolide and torvocizumab in neoadjuvant treatment for these patients, a prospective, multicenter, single-arm exploratory study is planned to provide valuable insights for developing neoadjuvant treatment regimens for advanced ovarian cancer.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Bai-Rong Xia, MD
- Número de teléfono: 18604516165
- Correo electrónico: xiabairong9999@126.com
Copia de seguridad de contactos de estudio
- Nombre: Yao Chen
- Correo electrónico: cyao49446@gmail.com
Ubicaciones de estudio
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Hefei, Porcelana
- Reclutamiento
- Anhui Cancer Hospital
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Contacto:
- bairong xia, MD
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Female participants aged ≥18 years and ≤75 years at enrollment;
- Histologically or cytologically confirmed diagnosis of epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma, with histopathological confirmation of high-grade serous carcinoma or endometrioid carcinoma, and FIGO stage (2014 edition) III-IV;
- Meeting the neoadjuvant indications for ovarian cancer (preoperative evaluation by a gynecologic oncologist indicates low likelihood of achieving R0 resection with initial debulking surgery, or the patient's physical condition is unsuitable for immediate surgery due to poor tolerance to PDS);
- Positive HRD testing result;
- Presence of at least one measurable lesion meeting RECIST 1.1 criteria;
- Expected survival time ≥12 weeks;
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
Absence of severe hematologic, cardiac, pulmonary, hepatic, renal dysfunction, or immunodeficiency disorders. Within one week prior to the first administration, the functional status of vital organs must meet the following requirements (supportive therapies such as any blood components or cell growth factors are prohibited within 14 days before the first dose):
- Complete blood count: HGB ≥ 90 g/L; WBC ≥ 4.0 × 10⁹/L; NEUT ≥ 2.0 × 10⁹/L; PLT ≥ 100 × 10⁹/L;
- Blood biochemistry: TBIL ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN; BUN and Cr ≤ 1.5 × ULN with creatinine clearance ≥ 50 mL/min;
- Coagulation function: INR ≤ 1.5 × ULN; APTT ≤ 1.5 × ULN;
- Within 4 weeks prior to the first dose, cardiac ultrasound must demonstrate: left ventricular ejection fraction (LVEF)> 50%;
- Pregnancy test results must be negative in patients of childbearing age, with voluntary use of effective and reliable contraceptive measures during the study;
- Participants must voluntarily enroll in the study, sign an informed consent form, demonstrate good compliance, and agree to participate in follow-up visits.
Exclusion Criteria:
- Ovarian cancer, fallopian tube cancer, primary peritoneal cancer (e.g., germ cell tumors), or ovarian tumors with low malignant potential (e.g., borderline tumors) of non-epithelial origin;
- Previous receipt of antitumor therapy, including but not limited to radiotherapy, chemotherapy, surgery, targeted therapy, and immunotherapy (Note: lymph node dissection or biopsy performed for clinical staging purposes using tissue obtained via puncture biopsy or laparoscopic exploration is permitted);
- History of other malignancies within the past 5 years, excluding cured localized tumors (e.g., basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, cervical carcinoma in situ, breast carcinoma in situ);
- Participation in other drug clinical trials and use of investigational drugs within 4 weeks prior to enrollment;
- Administration of live attenuated vaccines within 4 weeks before initial dosing or planned during the study period;
- Known history of allergy to any component of this regimen;
- Subjects with active infectious diseases;
- Subjects with any severe and/or uncontrolled diseases;
- Active autoimmune diseases requiring systemic treatment within 2 years prior to study initiation, or autoimmune diseases at risk of recurrence; exceptions include: non-systemically treatable dermatoses (e.g., vitiligo, alopecia, psoriasis, or eczema); hypothyroidism due to autoimmune thyroiditis requiring only stable hormone replacement therapy; well-controlled type 1 diabetes mellitus; and conditions deemed by investigators unlikely to recur without external triggers;
- Pregnant or breastfeeding women, or women of childbearing potential with positive baseline pregnancy test results.
- According to the investigator's assessment, the patient has a severe comorbid condition that poses significant risks to safety or impedes participation in the study, including but not limited to: severe hypertension uncontrolled by medication (systolic blood pressure ≥150 mmHg, diastolic blood pressure ≥100 mmHg), myocardial ischemia or myocardial infarction, severe arrhythmias, congestive heart failure grade ≥2, severe pulmonary dysfunction/disease, severe diabetes mellitus, or active infections;
- A documented history of neurological or psychiatric disorders, including epilepsy or dementia;
- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
- Known history of interstitial lung disease or non-infectious pneumonia;
- Diagnosis of immunodeficiency or ongoing systemic glucocorticoid therapy or any other form of immunosuppressive treatment;
- Presence of any condition increasing bleeding risk, such as severe hemorrhoids, acute gastritis, or gastric and duodenal ulcers;
- History of dysphagia or any gastrointestinal disorder affecting drug absorption;
- Any other circumstances deemed inappropriate for study participation by the investigator.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Study Medication Regimen
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Total resection rate (R0 resection rate)
Periodo de tiempo: 3-month
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All macroscopically visible tumor tissues were surgically removed, and no cancer cells were found at the surgical margins under microscopic examination.
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3-month
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Objective Response Rate (ORR)
Periodo de tiempo: 12-month
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refers to the proportion of patients whose tumor volume has decreased by 30% and maintained this reduction for more than four weeks, calculated as the sum of complete response (CR) and partial response (PR).
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12-month
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Disease Control Rate (DCR)
Periodo de tiempo: 12-month
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refers to the proportion of all cancer patients receiving a specific treatment who exhibit tumor shrinkage or stabilization, with this condition persisting for a defined period.
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12-month
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Progression-Free Survival (PFS)
Periodo de tiempo: 12-month
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refers to the time from randomization until the first occurrence of disease progression or death from any cause.
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12-month
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Pathological Complete Response rate (pCR rate)
Periodo de tiempo: 12-month
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absence of infiltrating tumor cells upon microscopic examination after resection of the primary tumor;
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12-month
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Overall Survival (OS)
Periodo de tiempo: 12-month
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refers to the time from randomization until death from any cause.
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12-month
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Adverse Events (AEs)
Periodo de tiempo: 12-month
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Collect all adverse events occurring in all subjects from the date of signing the informed consent form until 28 days after discontinuation of medication, including clinical symptoms and abnormalities in vital signs or laboratory tests.
Record their clinical manifestations, severity, occurrence time, duration, management measures, and prognosis, and assess their correlation with the investigational drug.
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12-month
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
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
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
- Enfermedades Genitales Femeninas
- Neoplasias de glándulas endocrinas
- Enfermedades Ováricas
- Enfermedades anexiales
- Neoplasias Genitales Femeninas
- Trastornos gonadales
- Neoplasias Ováricas
Otros números de identificación del estudio
- 2025-LLYJ-0153
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
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