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

Overview

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

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

Primary outcome measures

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

Secondary outcome measures (9)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 17 centers

• Beijing Obstetrics and Gynecology Hospital — Beijing
• Chongqing Cancer Hospital — Chongqing
• Fujian Cancer Hospital — Fuzhou
• SUN Yat-sen University Cancer Center — Guangzhou
• Guangxi Medical University Cancer Hospital — Nanning
• Harbin Medical University Cancer Hospital — Harbin
• Henan Cancer Hospital — Zhengzhou
• Hunan Cancer Hospital — Changsha
• … and 9 more centers

Identifiers

NCT: NCT06584032 · 2024-013-00CH1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗