Clinical trial NCT06475599: Anlotinib Hydrochloride Capsules Combined With TQB2450 in the Treatment of Endometrial Cancer
Official title: Efficacy of Anlotinib Hydrochloride Capsules Combined With TQB2450 in the Treatment of Endometrial Cancer in a Randomized, Controlled, Open-label, Multicenter Phase III Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Endometrial Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-06-26
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To demonstrate that anlotinib hydrochloride capsules combined with TQB2450 injection can significantly prolong progression-free survival (PFS) compared with chemotherapy in patients with recurrent or metastatic endometrial cancer that is non- microsatellite instability high (non-MSI-H) or DNA mismatch repair deficient (non-dMMR).


Eligibility criteria: Inclusion Criteria:

* Recurrent or metastatic advanced endometrial cancer confirmed by histopathology;
* Patients failed to respond to 1-2 lines of platinum-based doublet-based therapy;
* Provide a traceable MMR/MSI status report or provide biological samples for DNA mismatch repair/microsatellite instability (MMR/MSI) status testing with non-MSI-high (non-MSI-H) or non-dMMR；
* Patients who cannot undergo radical surgery/radiotherapy;
* Age: ≥18 years old (when signing the informed consent); Eastern Cooperative Oncology Group (ECOG) performance status (PS) score: 0-1; The expected survival time is more than 3 months；
* At least one measurable lesion (RECIST 1.1);
* Good function of the major organs；
* Women of childbearing age should agree that they must use a contraceptive method (e.g. Intra-uterine device (IUD), contraceptive pill, or condom) during the study and for 6 months after the study; A negative serum pregnancy test within 7 days before study entry and must be non-lactating；
* Subjects voluntarily joined this study, signed informed consent, and had good compliance；

Exclusion Criteria:

* Previous use of bevacizumab, endostar, anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, regorafenib, fruquintinib and other anti-angiogenic drugs or immunotherapy drugs targeting programmed cell death protein 1 (PD-1), PD-L1 and other related cells；
* Patients received anti-tumor indications of Chinese patent medicine approved by National Medical Products Administration (NMPA) within 2 weeks before the study treatment；
* Pathology suggested carcinosarcoma (malignant mullerian mixed tumor), endometrial leiomyosarcoma or other high-grade sarcoma, or endometrial stromal sarcoma；
* Hormone therapy for endometrial cancer had been received within 1 week before the first dose of trial medication；
* Surgery, chemotherapy, radiation therapy, or other anticancer therapy had been received within 4 weeks before the initiation of study treatment (the washout period was calculated from the end of the last treatment). The half-life of oral targeted drugs was less than 5 drugs；
* Subjects with known central nervous system metastases and/or carcinomatous meningitis; The patients were not asymptomatic or were treated and stable, had no radiographic evidence of new or expanding brain metastases for at least 2 weeks after treatment for brain metastases, and had discontinued steroids or anticonvulsant therapy for at least 14 days before the initiation of study treatment；
* The patient had developed or had concurrent malignant tumors within the past 3 years；
* Multiple factors that affect the oral administration of anlotinib (e.g., inability to swallow, post-gastrointestinal resection, chronic diarrhea, and intestinal obstruction) may affect the oral absorption of anlotinib；
* Uncontrolled pleural, pericardial, or ascites requiring repeated drainage (investigator judgment); Severe bone injury caused by tumor bone metastasis may occur or occur after enrollment；
* Patients whose imaging (CT or MRI) showed that the tumor had invaded the important blood vessels or the investigators judged that the tumor was likely to invade the important blood vessels and cause fatal hemorrhage during the follow-up study；
* Unmitigated toxic effects higher than CTCAE grade 1 due to any previous antineoplastic therapy, excluding alopecia；
* Major surgical treatment, open biopsy, or significant traumatic injury within 28 days before the first dose；
* A wound or fracture that has not healed for a long time；
* Patients with a history of arterial/venous thrombosis/cancer thrombosis within 6 months before the first dose of drug, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism；
* People who have a history of psychotropic drug abuse and cannot abstain from it or have mental disorders；
* Subjects with any severe and/or uncontrolled illness；
* A history of vaccination with live attenuated vaccine within 28 days before the initiation of study treatment or a planned vaccination with live attenuated vaccine during the study；
* Patients with severe allergic disease, history of severe drug allergy, and known allergic to any component of the trial drug prescription;；
* Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressive agents) had developed within 2 years before the initiation of study treatment；
* Patients who are diagnosed with immunodeficiency or who are receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (at a dose of \>10mg/ day of prednisone or other equivalent efficacy hormone) and continue to do so within 2 weeks before the first dose; Major surgical treatment or significant traumatic injury within 4 weeks before the first dose in this study；
* Participated in other clinical trials of antineoplastic drugs within 4 weeks before the first dose；
* Subjects with concomitant diseases that seriously endanger the safety of the subjects or interfere with the completion of the study, or those who were considered to be unsuitable for enrollment for other reasons according to the investigator's judgment.

Primary outcomes:
measure: Progression-free survival (PFS) assessed by independent imaging review committee (IRC)
timeFrame: Up to 36 months after study start
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 36 months after study start
measure: Progression-free survival (PFS) assessed by investigators
timeFrame: Up to 36 months after study start
measure: Objective mitigation rate (ORR)
timeFrame: Up to 36 months after study start
measure: Duration of Response (DOR)
timeFrame: Up to 36 months after study start
measure: Disease control rate (DCR)
timeFrame: Up to 36 months after study start
measure: Incidence and severity of abnormal laboratory values
timeFrame: Up to 36 months after study start
measure: Incidence and severity of adverse event rate Adverse events (AE), serious adverse event (SAE)
timeFrame: Up to 36 months after study start
measure: Incidence of dose interruptions, dose reductions, and dose discontinuations due to study-drug-related toxicity during the trial
timeFrame: Up to 36 months after study start
measure: Immunogenicity of TQB2450
timeFrame: Before administration (-15 minutes) in cycles 1, 2, 5, and 9, and 90 days after the last dose (±7days), each cycle is 21 days
measure: European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30)
timeFrame: Up to 96 weeks
measure: European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)
timeFrame: Up to 96 weeks
measure: European Organization for Research on Treatment of Cancer Endometrial cancer Specific scale QLQ-EN24
timeFrame: Up to 96 weeks
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Lanzhou
country: China
facility: First Hospital of Lanzhou University
state: Gansu
city: Lanzhou
country: China
facility: Gansu Provincial Cancer Hospital
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Huizhou
country: China
facility: Huizhou Central People's Hospital
state: Guangdong
city: Jiangmen
country: China
facility: Jiangmen Central Hospital
state: Guangdong
city: Meizhou
country: China
facility: Meizhou People's Hospital
state: Guangdong
city: Guigang
country: China
facility: Guigang City People's Hospital
state: Guangxi
city: Guilin
country: China
facility: Nanxishan Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Liuzhou
country: China
facility: Liuzhou People's Hospital
state: Guangxi
city: Liuzhou
country: China
facility: Liuzhou Municipal Liutie Central Hospital
state: Guangxi
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
state: Guangxi
city: Haikou
country: China
facility: Hainan Ceneral Hospital
state: Hainan
city: Tangshan
country: China
facility: Tangshan People's Hospital
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Nanyang
country: China
facility: Nanyang first People's Hospital National Third Class A Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Shaoyang
country: China
facility: The Central Hospital Of Shaoyang
state: Hunan
city: Hohhot
country: China
facility: Inner Mongolia Autonomous Region People's Hospital
state: Inner Mongolia Autonomous Region
city: Changchun
country: China
facility: Changchun Tumor Hospital
state: Jilin
city: Changchun
country: China
facility: The first hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital Of China Medical University
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital Of Ningxia Medical University
state: Ningxia
city: Xining
country: China
facility: Qinghai Red Cross Hospital
state: Qinghai
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Air Force Medical University
state: Shaanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi 'an Jiaotong University
state: Shaanxi
city: Xi'an
country: China
facility: Shaanxi Provincial People's Hospital
state: Shaanxi
city: Binzhou
country: China
facility: Binzhou Medical University Hospital
state: Shandong
city: Binzhou
country: China
facility: Binzhou People's Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Weifang
country: China
facility: Weifang People's Hospital
state: Shandong
city: Weifang
country: China
facility: Yidu Central Hospital Of Weifang
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Zaozhuang
country: China
facility: Tengzhou Central People's Hospital
state: Shandong
city: Taiyuan
country: China
facility: Shanxi Cancer hospital
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Ürümqi
country: China
facility: Affiliated Cancer Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: Maternal Health School of Medicine Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Ningbo
country: China
facility: The Affiliated People's Hospital of Ningbo University
state: Zhejiang
city: Beijing
country: China
facility: Beijing Obstetrics and Gynecology Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Chaoyang Hospital, Capital Medical University
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Chongqing
country: China
facility: The Southwest Hospital of Amu
city: Chongqing
country: China
facility: Chongqing University Three Gorges Hospital
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
city: Chongqing
country: China
facility: The Affiliated Hospital of Southwest Medical University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital
city: Shanghai
country: China
facility: Obstetrics & Gynecology Hospital of Fudan University
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Tianjin
country: China
facility: Tianjin Central Hospital of Gynecology Obstetrics
Study officials:
References: