Advanced Endometrial Cancer
Conditions
Keywords
fruquintinib, sintilimab, endometrial cancer
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
Interventions
DRUGfruquintinib
Fruquintinib will be orally administrated once daily for 2 consecutive weeks followed by a 1-week break.
BIOLOGICALsintilimab
Sintilimab will be intravenously administrated on Day 1 every three weeks.
DRUGpaclitaxel
175 mg/m\^2 via IV infusion, once a week for 3 weeks followed by a 1-week break.
DRUGdoxorubicin
60mg/m\^2 via IV infusion, on Day 1 every three weeks.
Sponsors
Hutchmed
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) as assessed by IRC | Up to approximately 4 years | Progression-free survival (PFS) is defined as the time from randomization to disease progression assessed by IRC or death due to any cause, whichever occurs first. |
| Overall Survival (OS) | Up to approximately 4 years | Overall Survival (OS) is defined as the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | Up to approximately 4 years | Disease Control Rate (DCR) is defined as the ratio of patients who reached complete response (CR) or partial response (PR) or maintained a stable disease, as assessed by IRC and investigator. |
| Time To Response (TTR) | Up to approximately 4 years | Time To Response (TTR) is defined as the time from the start of treatment to the first objective response rate (ORR) ,as assessed by IRC and investigator. |
| Progression-Free Survival (PFS) as assessed by investigator | Up to approximately 4 years | Progression-Free Survival is defined as the time from randomization to disease progression assessed by investigator or death due to any cause, whichever occurs first. |
| Objective Response Rate (ORR) | Up to approximately 4 years | Objective Response Rate (ORR) is defined as the ratio of patients who reached complete response (CR) or partial response (PR) , as assessed by IRC and investigator. |
| Blood concentration of fruquintinib | At the end of cycle 4 day 14 (each cycle is 21 days) | Steady-state blood concentration of fruquintinib |
| Health-related quality of life (using EORTC QLQ-C30) | Up to approximately 4 years | Changes in EORTC QLQ-C30(European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) scores from baseline |
| Health-related quality of life (using EORTC QLQ-EN24) | Up to approximately 4 years | Changes in EORTC QLQ-EN24 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Endometrial Cancer Module) scores from baseline |
| Incidence and severity of Treatment-emergent Adverse Events (TEAE) | Up to approximately 4 years | Adverse events classified according to NCI CTCAE version 5.0 |
| Duration of Response (DoR) | Up to approximately 4 years | For patients who reached complete response (CR) or partial response (PR), Duration of Response (DoR) is defined as the time from the first CR or PR until disease progression or death due to any cause, whichever occurs first ,as assessed by IRC and investigator. |
Countries
China
Contacts
Primary ContactPanfeng Tan
Outcome results
None listed