Study of Fruquintinib Plus Sintilimab for Treatment of Advanced Endometrial Cancer

Официальное название

A Randomized,Open-label,Multicenter Phase III Clinical Study to Evaluate the Efficacy and Safety of Fruquintinib Plus Sintilimab Versus Chemotherapy of the Treating Physician's Choice as Second-line Treatment for Advanced Endometrial Cancer

Обзор

The goal of this study is to evaluate whether fruquintinib(HMPL-013) plus sintilimab(IBI308) is safe and effective in the treatment of advanced endometrial cancer(EMC).

Подробное описание

A randomized, open, positive-controlled, multicenter Phase III clinical study to compare the efficacy and safety of fruquintinib(HMPL-013) plus sintilimab(IBI308) versus chemotherapy in patients with advanced endometrial cancer who have progressed after first-line standard chemotherapy

Вмешательства

• Препарат fruquintinib
  Fruquintinib will be orally administrated once daily for 2 consecutive weeks followed by a 1-week break.
• Биопрепарат sintilimab
  Sintilimab will be intravenously administrated on Day 1 every three weeks.
• Препарат paclitaxel
  175 mg/m\^2 via IV infusion, once a week for 3 weeks followed by a 1-week break.
• Препарат doxorubicin
  60mg/m\^2 via IV infusion, on Day 1 every three weeks.

Первичные конечные точки

• Progression-Free Survival (PFS) as assessed by IRC [Срок оценки: Up to approximately 4 years]
• Overall Survival (OS) [Срок оценки: Up to approximately 4 years]

Вторичные конечные точки (9)

• Objective Response Rate (ORR) [Срок оценки: Up to approximately 4 years]
• Duration of Response (DoR) [Срок оценки: Up to approximately 4 years]
• Disease Control Rate (DCR) [Срок оценки: Up to approximately 4 years]
• Time To Response (TTR) [Срок оценки: Up to approximately 4 years]
• Progression-Free Survival (PFS) as assessed by investigator [Срок оценки: Up to approximately 4 years]
• Incidence and severity of Treatment-emergent Adverse Events (TEAE) [Срок оценки: Up to approximately 4 years]
• Blood concentration of fruquintinib [Срок оценки: At the end of cycle 4 day 14 (each cycle is 21 days)]
• Health-related quality of life (using EORTC QLQ-C30) [Срок оценки: Up to approximately 4 years]
• Health-related quality of life (using EORTC QLQ-EN24) [Срок оценки: Up to approximately 4 years]

Критерии участия

Критерии включения

• Have fully understood and voluntarily signed the informed consent form
• Age 18 to 75 years (inclusive) ; Body mass index (BMI) ≥ 18.5kg/m\^2;
• Histologically or cytologically confirmed advanced or recurrent endometrial cancer with measurable lesions
• Patients who previously failed first-line systemic platinum-based therapy
• ECOG PS (Eastern Cooperative Oncology Group performance status score) 0 or 1;
• Need to provide tumor samples for central lab testing of biomarkers such as MSI(microsatellite instability) status;
• Non-MSI-H(non-microsatellite instability-high) by central lab or previous test result indicating pMMR(proficient mismatch repair);
• Adequate function of the major organs;
• Expected survival ≥ 12 weeks;
• Female patients of childbearing potential must have a negative serum pregnancy test within 7 days before randomization.

Критерии исключения

• Endometrial carcinosarcoma or sarcoma;
• Known MMR(mismatch repair)/MSI status with dMMR(deficient mismatch repair) or MSI-H(microsatellite instability-high);
• Toxicities related to prior anticancer therapy did not recover to ≤CTCAE Grade 1, except alopecia and oxaliplatin-induced peripheral neurotoxicity ≤CTCAE Grade 2;
• Received systemic anti-tumor therapy approved within 4 weeks before randomization;
• Other malignancies within the past 5 years;
• Previous or screening central nervous system (CNS) metastases;
• Radical radiotherapy within 4 weeks before randomization
• Previously received any anti-programmed cell death receptor-1 (PD-1) antibody, anti-PD-L1(programmed death ligand-1) antibody, anti-PD-L2(programmed death ligand-2) antibody, or anti cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody or any other antibody acting on T cell costimulation or checkpoint pathways (eg, OX40, CD137, etc) or small molecule vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors;
• Symptomatic or treatment-requiring thyroid dysfunction at screening;
• Use of immunosuppressive agents within 4 weeks before randomization
• Presence of any active autoimmune disease requiring systemic treatment or history of autoimmune disease within the past 2 years;
• Systemic immunostimulants within 4 weeks before randomization;
• Administration of any live or live-attenuated vaccine within 4 weeks before randomization or planned during the study;
• Major surgical procedures within 4 weeks before randomization;
• Uncontrolled malignant pleural effusion, ascites or pericardial effusion;
• Patients with current hypertension uncontrolled by medication;
• Patients with any current disease or condition affecting drug absorption, or patients unable to take oral medications;
• Receiving strong inducers of cytochrome P450 3A4 enzyme;
• Patients with gastrointestinal diseases or unresected tumors with active bleeding, or other conditions that may cause gastrointestinal bleeding and perforation as judged by the investigator; or with gastrointestinal perforation or gastrointestinal fistula, which is not recovered after surgical treatment;
• Active bleeding within 3 weeks before randomization, or melena, or bleeding from a tumor within 2 weeks before the first dose ;
• Tumor invading major vascular structures and is judged by the investigator to be at greater risk of massive haemorrhage;
• Patients who had arterial thrombosis or deep venous thrombosis within 6 months before randomization; or patients who had stroke events and/or transient ischemic attack within 12 months; patients who had thrombosis caused by implantable intravenous infusion pump or catheter, except patients who had stable thrombosis after conventional anticoagulant therapy;
• Clinically significant cardiovascular disease;
• Clinically significant electrolyte abnormalities as judged by the investigator;
• Active infection or fever of unknown origin before randomization;
• Patients with active pulmonary tuberculosis (TB) receiving anti-tuberculosis treatment or anti-tuberculosis treatment within 1 year before randomization;
• Patients with previous and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severely impaired pulmonary function, which may interfere with the detection and management of suspected drug-related pulmonary toxicity; previous or current (non-infectious) pulmonary inflammation requiring steroid hormone therapy;
• Positive human immunodeficiency virus (HIV) antibody screening;
• Known history of clinically significant liver disease
• Known hypersensitivity to any of the study drugs or any of their excipients, or previous history of serious hypersensitivity to any other monoclonal antibody;
• Patients who have received other clinical drugs that have not been approved or marketed within 4 weeks before randomization;
• Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
• Patients who have received tissue/organ transplantation;
• Patients with known psychiatric disorders or substance abuse disorders that could affect study compliance;
• Patients who, in the opinion of the investigator, have other reasons that would make them inappropriate for this clinical study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 17 центров

• Beijing Obstetrics and Gynecology Hospital — Пекин
• Chongqing Cancer Hospital — Чунцин
• Fujian Cancer Hospital — Фучжоу
• SUN Yat-sen University Cancer Center — Гуанчжоу
• Guangxi Medical University Cancer Hospital — Nanning
• Harbin Medical University Cancer Hospital — Харбин
• Henan Cancer Hospital — Чжэнчжоу
• Hunan Cancer Hospital — Чанша
• … и ещё 9 центров

Идентификаторы

NCT: NCT06584032 · 2024-013-00CH1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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