Clinical trial NCT06584032: Study of Fruquintinib Plus Sintilimab for Treatment of Advanced Endometrial Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Advanced Endometrial Cancer
Keywords: fruquintinib
sintilimab
endometrial cancer
Lead sponsor: Hutchmed
Sponsor class: INDUSTRY
First posted: 2024-09-04
Enrollment: 412
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. Endometrial carcinosarcoma or sarcoma;
2. Known MMR(mismatch repair)/MSI status with dMMR(deficient mismatch repair) or MSI-H(microsatellite instability-high);
3. Toxicities related to prior anticancer therapy did not recover to ≤CTCAE Grade 1, except alopecia and oxaliplatin-induced peripheral neurotoxicity ≤CTCAE Grade 2;
4. Received systemic anti-tumor therapy approved within 4 weeks before randomization;
5. Other malignancies within the past 5 years;
6. Previous or screening central nervous system (CNS) metastases;
7. Radical radiotherapy within 4 weeks before randomization
8. 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;
9. Symptomatic or treatment-requiring thyroid dysfunction at screening;
10. Use of immunosuppressive agents within 4 weeks before randomization
11. Presence of any active autoimmune disease requiring systemic treatment or history of autoimmune disease within the past 2 years;
12. Systemic immunostimulants within 4 weeks before randomization;
13. Administration of any live or live-attenuated vaccine within 4 weeks before randomization or planned during the study;
14. Major surgical procedures within 4 weeks before randomization;
15. Uncontrolled malignant pleural effusion, ascites or pericardial effusion;
16. Patients with current hypertension uncontrolled by medication;
17. Patients with any current disease or condition affecting drug absorption, or patients unable to take oral medications;
18. Receiving strong inducers of cytochrome P450 3A4 enzyme;
19. 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;
20. Active bleeding within 3 weeks before randomization, or melena, or bleeding from a tumor within 2 weeks before the first dose ;
21. Tumor invading major vascular structures and is judged by the investigator to be at greater risk of massive haemorrhage;
22. 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;
23. Clinically significant cardiovascular disease;
24. Clinically significant electrolyte abnormalities as judged by the investigator;
25. Active infection or fever of unknown origin before randomization;
26. Patients with active pulmonary tuberculosis (TB) receiving anti-tuberculosis treatment or anti-tuberculosis treatment within 1 year before randomization;
27. 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;
28. Positive human immunodeficiency virus (HIV) antibody screening;
29. Known history of clinically significant liver disease
30. Known hypersensitivity to any of the study drugs or any of their excipients, or previous history of serious hypersensitivity to any other monoclonal antibody;
31. Patients who have received other clinical drugs that have not been approved or marketed within 4 weeks before randomization;
32. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
33. Patients who have received tissue/organ transplantation;
34. Patients with known psychiatric disorders or substance abuse disorders that could affect study compliance;
35. Patients who, in the opinion of the investigator, have other reasons that would make them inappropriate for this clinical study.

Primary outcomes:
measure: Progression-Free Survival (PFS) as assessed by IRC
timeFrame: Up to approximately 4 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 4 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 4 years
measure: Duration of Response (DoR)
timeFrame: Up to approximately 4 years
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 4 years
measure: Time To Response (TTR)
timeFrame: Up to approximately 4 years
measure: Progression-Free Survival (PFS) as assessed by investigator
timeFrame: Up to approximately 4 years
measure: Incidence and severity of Treatment-emergent Adverse Events (TEAE)
timeFrame: Up to approximately 4 years
measure: Blood concentration of fruquintinib
timeFrame: At the end of cycle 4 day 14 (each cycle is 21 days)
measure: Health-related quality of life (using EORTC QLQ-C30)
timeFrame: Up to approximately 4 years
measure: Health-related quality of life (using EORTC QLQ-EN24)
timeFrame: Up to approximately 4 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Obstetrics and Gynecology Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: SUN Yat-sen University Cancer Center
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
state: Guangxi
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Xian
country: China
facility: Xijing Hospital of Air Force Military Medical University
state: Shaanxi
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Taiyuan
country: China
facility: Sencond Hospital of Shanxi Medical University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Women's Hospital school of Medical Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Fudan University
name: Xiaohua Wu
role: PRINCIPAL_INVESTIGATOR
References: