Study of Fruquintinib Plus Sintilimab for Treatment of Advanced Endometrial Cancer

January 5, 2025 updated by: Hutchmed

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

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Estimated)

412

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100026
        • Not yet recruiting
        • Beijing Obstetrics and Gynecology Hospital
        • Contact:
    • Chongqing
      • Chongqing, Chongqing, China, 400030
        • Not yet recruiting
        • Chongqing Cancer Hospital
        • Contact:
    • Fujian
      • Fuzhou, Fujian, China, 350014
        • Not yet recruiting
        • Fujian Cancer Hospital
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China, 510050
        • Not yet recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:
    • Guangxi
      • Nanning, Guangxi, China, 530012
        • Recruiting
        • Guangxi Medical University Cancer Hospital
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150081
        • Not yet recruiting
        • Harbin Medical University Cancer Hospital
        • Contact:
    • Henan
      • Zhengzhou, Henan, China, 450003
        • Recruiting
        • Henan Cancer Hospital
        • Contact:
    • Hunan
      • Changsha, Hunan, China, 410031
        • Not yet recruiting
        • Hunan Cancer Hospital
        • Contact:
    • Shaanxi
      • Xian, Shaanxi, China, 710032
        • Not yet recruiting
        • Xijing Hospital of Air Force Military Medical University
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 250117
        • Not yet recruiting
        • Shandong Cancer Hospital
        • Contact:
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:
    • Shanxi
      • Taiyuan, Shanxi, China, 030001
        • Not yet recruiting
        • Sencond Hospital of Shanxi Medical University
        • Contact:
    • Tianjin
      • Tianjin, Tianjin, China, 300060
        • Not yet recruiting
        • Tianjin Medical University Cancer Institute & Hospital
        • Contact:
    • Yunnan
      • Kunming, Yunnan, China, 650118
        • Not yet recruiting
        • Yunnan Cancer Hospital
        • Contact:
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310005
        • Not yet recruiting
        • Zhejiang Cancer Hospital
        • Contact:
      • Hangzhou, Zhejiang, China, 310003
        • Not yet recruiting
        • Women's Hospital school of Medical Zhejiang University
        • Contact:
      • Wenzhou, Zhejiang, China, 325015
        • Not yet recruiting
        • The First Affiliated Hospital of Wenzhou Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental group
Patients will be treated with a planned dose of fruquintinib and sintilimab every three weeks until an IRC (independent review committee)-confirmed PD(disease progression) or meeting other discontinuation criteria.
Drug: fruquintinib
Fruquintinib will be orally administrated once daily for 2 consecutive weeks followed by a 1-week break.
Other Names:
  • HMPL-013
Biological: sintilimab
Sintilimab will be intravenously administrated on Day 1 every three weeks.
Other Names:
  • IBI308
Active Comparator: Control group
Patients will be treated with TPC (chemotherapy of treating physician's choice, paclitaxel or doxorubicin) every three or four weeks until IRC-confirmed PD or meeting other discontinuation criteria.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS) as assessed by IRC
Time Frame: 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.
Up to approximately 4 years
Overall Survival (OS)
Time Frame: Up to approximately 4 years
Overall Survival (OS) is defined as the time from randomization to death due to any cause.
Up to approximately 4 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: 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.
Up to approximately 4 years
Duration of Response (DoR)
Time Frame: 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.
Up to approximately 4 years
Disease Control Rate (DCR)
Time Frame: 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.
Up to approximately 4 years
Time To Response (TTR)
Time Frame: 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.
Up to approximately 4 years
Progression-Free Survival (PFS) as assessed by investigator
Time Frame: 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.
Up to approximately 4 years
Incidence and severity of Treatment-emergent Adverse Events (TEAE)
Time Frame: Up to approximately 4 years
Adverse events classified according to NCI CTCAE version 5.0
Up to approximately 4 years
Blood concentration of fruquintinib
Time Frame: At the end of cycle 4 day 14 (each cycle is 21 days)
Steady-state blood concentration of fruquintinib
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
Changes in EORTC QLQ-C30(European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30) scores from baseline
Up to approximately 4 years
Health-related quality of life (using EORTC QLQ-EN24)
Time Frame: 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
Up to approximately 4 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hutchmed

Investigators

  • Principal Investigator: Xiaohua Wu, Fudan University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 12, 2024

Primary Completion (Estimated)

January 8, 2029

Study Completion (Estimated)

June 9, 2029

Study Registration Dates

First Submitted

August 21, 2024

First Submitted That Met QC Criteria

September 1, 2024

First Posted (Actual)

September 4, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 5, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-013-00CH1

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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