Trial Title:
Efficacy and Safety of TQB2450 Injection Combined With Chemotherapy ± Anlotinib Hydrochloride Capsules for Advanced Endometrial Cancer or Sarcoma of Uterus.
NCT ID:
NCT05481645
Condition:
Advanced Endometrial Cancer
Sarcoma of Uterus
Conditions: Official terms:
Sarcoma
Endometrial Neoplasms
Paclitaxel
Docetaxel
Carboplatin
Gemcitabine
Doxorubicin
Liposomal doxorubicin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
TQB2450 injection
Description:
TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1),
which prevents the binding of PD-L1 to PD-1 and B7.1 receptors on the surface of T cells,
thereby reactivating T cells and enhancing the immune response.
Arm group label:
Group one
Arm group label:
Group three
Arm group label:
Group two
Intervention type:
Drug
Intervention name:
Anlotinib Hydrochloride Capsule
Description:
Anlotinib hydrochloride is a muti-target tyrosine kinase inhibitor.
Arm group label:
Group three
Arm group label:
Group two
Intervention type:
Drug
Intervention name:
Carboplatin Injection
Description:
Carboplatin which s similar to alkylating agent, is a second-generation platinum
anti-tumor drug, which mainly causes cross-linking of DNA within and between chains,
destroys DNA molecules, and disintegrates the helix.
Arm group label:
Group one
Arm group label:
Group two
Intervention type:
Drug
Intervention name:
Paclitaxel Injection
Description:
Paclitaxel is a diterpene alkaloid with anticancer activity
Arm group label:
Group one
Arm group label:
Group two
Intervention type:
Drug
Intervention name:
Doxorubicin Hydrochloride Injection
Description:
Doxorubicin hydrochloride is a cycle non-specific anticancer chemotherapy drug, which
directly acts on DNA, changes the nature of DNA template, and inhibits DNA polymerase.
Arm group label:
Group three
Intervention type:
Drug
Intervention name:
Gemcitabine Hydrochloride Injection
Description:
Gemcitabine is a cell cycle specific antimetabolic drug, which mainly acts on tumor cells
at the DNA synthesis stage.
Arm group label:
Group three
Intervention type:
Drug
Intervention name:
Docetaxel injection
Description:
Docetaxel is an anti-tumor drug of paclitaxel, which plays an anti-tumor role by
interfering with the microtubule network necessary for cell Mitosis and interphase cell
function.
Arm group label:
Group three
Summary:
This study plans to enroll 69 subjects of endometrial cancer and 5-10 subjects of sarcoma
of uterus. The experimental set is divided into lead-in trial and formal trial. The
lead-in trial includes 9 subjects to observe the safety of the combination and determine
the dosage of anlotinib dihydrochloride capsules before the formal phase.
The formal trial includes 60 subjects of endometrial cancer and 5-10 subjects of sarcoma
of uterus. The purpose is to evaluate efficacy and safety of TQB2450 injection combined
with chemotherapy ± anlotinib hydrochloride capsules for first-line treatment and
maintenance treatment of patient with advanced endometrial cancer or sarcoma of uterus,
and explore biomarkers related to efficacy, mechanism of action, safety and/or
pathological mechanisms, the surgical conversion rate. ORR is the primary endpoint.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The subjects voluntarily participated in this study, signed the informed consent,
and had good compliance;
- Age: ≥18 years old (when signing the informed consent form); ECOG PS score: 0-1;
expected survival period of more than 3 months; body mass index (BMI) > 18.5 and
weight > 40kg;
- Who have not received first-line systemic anticancer therapy and are not suitable
for receiving treatment other than systemic treatment:
1. Group 1 and 2: Stage III/IV epithelial endometrial cancer (including
endometrioid carcinoma, non-endometrioid carcinoma, carcinosarcoma) confirmed
by histopathology, and the subject also needs to meet one of the following
categories:
1. Newly diagnosed subjects: there are still residual lesions visible on
imaging after non-radical surgery;
2. Subjects with initial recurrence: if the subject received systemic
platinum-based adjuvant and/or neoadjuvant chemotherapy,and the recurrence
time is more than 6 months from the end of the last chemotherapy,then the
previous chemotherapy is allowed.
2. Group 3: Stage I-IV sarcoma of uterus, and the subject also needs to meet one
of the following categories:
1. Newly diagnosed/initial recurrence subject of high grade endometrial
stromal sarcoma (ESS)、undifferentiated Uterine sarcoma (UUS) , uterine
Leiomyosarcoma and adenosarcoma(uLMS) with sarcoma overgrowth (OS). The
definition of new diagnosis and initial recurrence is the same as above.
2. Low grade ESS, adenosarcoma without SO and other Uterine sarcoma with
ER+/PR+,the subjects who failed in antiestrogen treatment.
- According to the RECIST 1.1 criteria, there is at least one measurable lesion. If
the measurable lesion is located in the area of previous radiotherapy, it should be
clearly defined as progressing state;
- Tumor tissue samples can be provided to detect MSI/MMR status or traceable test
reports;
- The main organs function well and meet the following standards:
1. Blood routine examination standards (no blood transfusion within 7 days before
screening, no correction with hematopoietic stimulating factor drugs):
1. Hemoglobin (HGB) ≥90 g/L;
2. The absolute value of neutrophils (NEUT)≥1.5×109/L;
3. Platelet count (PLT) ≥ 90 × 109/L;
2. The biochemical examination shall meet the following standards:
1. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN);
2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤
2.5×ULN. If accompanied by liver metastasis, ALT and AST≤5×ULN;
3. Serum creatinine (Cr) ≤ 1.5×ULN or creatinine clearance (Ccr) ≥ 60ml/min;
4. Serum albumin (ALB)>30g/L;
3. Urine routine examination standard: urine routine indicates urine protein <++;
if urine protein ≥++, it is necessary to confirm the 24-hour urine protein
quantitative ≤1.0g;
4. Coagulation function or thyroid function tests should meet the following
criteria:
1. Prothrombin time (PT), activated partial thromboplastin time (APTT),
international normalized ratio (INR) ≤ 1.5×ULN (no anticoagulation
therapy);
2. Thyroid-stimulating hormone (TSH) ≤ ULN; T3 and T4 levels should be
investigated if abnormal, and normal T3 and T4 levels can be selected.
5. Echocardiography assessment: Left ventricular ejection fraction (LVEF) ≥50%.
6. 12-lead electrocardiogram evaluation: QTc<470ms.
- Female subjects should agree that contraceptive measures (such as intrauterine
devices or condoms) must be used during the study period and within 6 months after
the end of the study; the serum pregnancy test must be negative within 7 days before
study enrollment, and must be Non-lactating subjects.
Exclusion Criteria:
- Tumor disease and medical history:
1. Other malignant tumors that have occurred or are currently concurrently present
within 3 years. The following conditions were eligible for enrollment: other
malignancies treated with a single surgery, achieving 5 consecutive years of
disease-free survival (DFS); cured cervical carcinoma in situ, non-melanoma
skin cancer, and superficial bladder tumors [Ta ( non-invasive tumor), Tis
(carcinoma in situ) and T1 (tumor-infiltrating basement membrane)];
2. Pathologically suggested endometrial leiomyosarcoma, endometrial stromal
sarcoma, undifferentiated uterine sarcoma or other high-grade sarcoma
(Applicable to group 1 and 2), Pathologically suggested epithelial endometrial
cancer or Carcinosarcoma (Applicable to group 3);
3. The presence of tumor thrombus, spinal cord compression caused by bone
metastases, brain metastases or cancerous meningitis;
4. Imaging (CT or MRI) shows that the tumor has invaded around important blood
vessels or the investigator judges that the tumor is very likely to invade
important blood vessels and cause fatal bleeding during the follow-up study;
5. Severe bone damage caused by tumor bone metastasis; including weight-bearing
bone pathological fractures and spinal cord compression that occurred within 6
months or predicted by the investigator to be likely to occur in the near
future;
6. Uncontrolled pleural effusion, pericardial effusion or ascites judged by the
investigator that still needs repeated drainage.
- Previous anti-tumor therapy or concomitant medication (the washout period is
calculated from the end of the last treatment):
1. Previously received anti-angiogenesis drugs, related immunotherapy drugs for
PD-1, PD-L1, CTLA-4;
2. Received drugs with immunomodulatory function, chemotherapy, radiotherapy,
clinical trial drug treatment, traditional Chinese medicine or proprietary
Chinese medicine with anti-tumor indications, or other anti-cancer therapy
within 4 weeks before receiving the study drug for the first time;
3. Received hormone therapy for endometrial cancer within 1 week before receiving
the first study drug treatment;
4. It is not satisfied that at least 5 half-lives have elapsed from the last use
of the targeted drug to the first receiving of the study drug, if it is a
combination drug, the drug with the longest half-life shall be calculated;
5. Those who have undergone major surgery, major surgical treatment, incisional
biopsy, obvious traumatic injury, or have not recovered sufficiently from
previous surgery in the judgment of the investigator within 3 weeks before the
first treatment with the study drug, or are expected to be required during the
study period. Major surgery;
6. The toxicity related to previous anti-tumor therapy has not recovered to CTCAE
≤ grade 1, except for alopecia and grade 2 peripheral neuropathy.
- Comorbid diseases and medical history:
1. History of liver-related diseases: a. Decompensated cirrhosis; b. Active or
chronic hepatitis; c. Bleeding disease secondary to hepatic insufficiency.
2. Kidney related medical history: a. Renal failure requiring hemodialysis or
peritoneal dialysis; b. Past or existing nephrotic syndrome, chronic nephritis.
3. Cardiovascular and cerebrovascular related medical history: a. Suffering from
epilepsy and requiring treatment; b. New York Heart Association class II-IV
heart failure, second-degree or higher heart block, myocardial infarction
within the past 6 months or Arterial thrombosis events, unstable arrhythmia or
unstable angina; c. Cerebrovascular accident, cerebral infarction, etc. within
6 months; d. If the treatment can adequately control blood pressure, the group
is allowed to enter the group; e. Past or current heart valve inflammation,
endocarditis; f. Cardiovascular syncope, pathological ventricular arrhythmia.
4. Gastrointestinal-related medical history: a. Inability to take oral
medications; b. History of malabsorption syndrome or other diseases that
interfere with gastrointestinal absorption; c. Active peptic ulcer or ulcerated
lower gastrointestinal tract in the past 6 months Treated for inflammation; d.
Persistent chronic diarrhea of grade 2 and above despite maximum medical
treatment.
5. Lung-related medical history: a. History of idiopathic pulmonary fibrosis,
organized pneumonia, drug-induced pneumonia, idiopathic pneumonia, or evidence
of active pneumonia found on chest CT scan during screening; b. Bronchodilator
required Medically intervened bronchial asthma; c. The clinical manifestations
are suspected to be tuberculosis, T-SPOT positive is judged by the investigator
to have tuberculosis infection or active tuberculosis within 1 year before
enrollment;
6. Endocrine-related medical history: a. Poor control of type I or II diabetes; b.
History of pituitary or adrenal dysfunction; c. Thyroid-stimulating hormone
(TSH) > ULN, if T3 and T4 levels are normal, they can be enrolled.
7. Immune-related medical history: a. A history of immunodeficiency, including HIV
positive or other acquired and congenital immunodeficiency diseases; b. Organ
transplantation planned or previously received, or hematopoietic stem cells
received within 60 days before the first dose Transplant, or have obvious host
transplant response; c. Active autoimmune disease; d. Systemic or topical
immunosuppressive or hormonal therapy is required to achieve immunosuppression,
and continue to be used within 7 days before the first dose Glucocorticoids, or
patients who still need immunosuppressive drugs within 5 half-lives before the
first dose.
8. Bleeding risk: a. Suffering from bleeding (hemoptysis), coagulation disease or
using warfarin, aspirin and other antiplatelet aggregation drugs (except
aspirin ≤100 mg/d for prophylaxis); b. Regardless of severity, there are any
signs or history of bleeding constitution; c. within 4 weeks before the first
dose, any CTC AE ≥ grade 3 bleeding or bleeding events;
9. The patient has an active systemic infection or an excessive viral load;
10. Combining serious or not well-controlled diseases or diseases that the
investigator determines may have a greater risk or affect the completion of the
study, including but not limited to: a. History of clear neurological or mental
disorders; b. Treponema pallidum specific antibody positive.
11. Those who have a history of drug abuse and cannot quit or have a history of
drug use.
- Research and treatment related:
1. History of vaccination with live attenuated vaccine within 28 days before the
start of study treatment, inactivated vaccine within 7 days, or planned
vaccination during the study period;
2. Those who have a history of severe allergic diseases, severe drug allergies,
and are known to be allergic to macromolecular protein preparations or TQB2450
injection or any components in the prescription of Anlotinib capsules, their
adjuvants and similar drugs;
- Subjects with insufficient compliance or other reasons are not suitable for
enrollment after the investigator's assessment.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen Memorial Hospital
Address:
City:
Guangzhou
Zip:
510120
Country:
China
Status:
Recruiting
Contact:
Last name:
Ke Wang, Doctor
Contact backup:
Phone:
18622221098
Email:
18622080116@163.com
Facility:
Name:
Zhongnan Hospital of Wuhan University
Address:
City:
Wuhan
Zip:
430062
Country:
China
Status:
Recruiting
Contact:
Last name:
Dapeng Li
Phone:
+86 15553115531
Email:
drldp@126.com
Facility:
Name:
Hunan Cancer Hospital
Address:
City:
Changsha
Zip:
410013
Country:
China
Status:
Recruiting
Contact:
Last name:
Ruifang An
Phone:
+86 18991232090
Email:
anruifang@163.com
Facility:
Name:
Taizhou People's Hospital
Address:
City:
Taizhou
Zip:
225399
Country:
China
Status:
Recruiting
Contact:
Last name:
Hui Qiu, Doctor
Phone:
+86 18986255160
Email:
qiuhuiznyy@whu.edu.cn
Facility:
Name:
Liaoning Cancer Hospital & Institute
Address:
City:
Shenyang
Zip:
110801
Country:
China
Status:
Recruiting
Contact:
Last name:
Keqiang Zhang, Doctor
Phone:
+86 13054196067
Email:
zhangkeqiang@hnca.org.cn
Facility:
Name:
The First Affiliated Hospital of Xi'an Jiaotong University
Address:
City:
Xi'an
Zip:
710061
Country:
China
Status:
Recruiting
Contact:
Last name:
Hua Qian, Doctor
Phone:
+86 13515155623
Email:
qhtzry@163.com
Facility:
Name:
Shandong Cancer Hospital
Address:
City:
Jinan
Zip:
250117
Country:
China
Status:
Recruiting
Contact:
Last name:
Yongjie Zhang, Doctor
Phone:
+86 18762096966
Email:
zhangyj0818@126.com
Facility:
Name:
Linyi Cancer Hospital
Address:
City:
Linyi
Zip:
276002
Country:
China
Status:
Recruiting
Contact:
Last name:
Ying Yang, Doctor
Phone:
15966506506
Email:
hxdany2004@126.com
Facility:
Name:
Yantai Yuhuangding Hospital
Address:
City:
Yantai
Zip:
264099
Country:
China
Status:
Recruiting
Contact:
Last name:
Bingzhong Zhang, Doctor
Phone:
13925063030
Email:
13925063030@163.com
Facility:
Name:
Obstetrics & Gynecology Hospital of Fudan University
Address:
City:
Shanghai
Zip:
200090
Country:
China
Status:
Recruiting
Contact:
Last name:
Xiumin Li, Doctor
Phone:
13583991399
Email:
Lyzlyylxm@163.com
Facility:
Name:
TianJin Medical University Cancer Institute & Hopspital
Address:
City:
Tianjin
Zip:
300181
Country:
China
Status:
Recruiting
Contact:
Last name:
Chunyan Wang, Doctor
Phone:
18900918586
Email:
lnzlgyn@163.com
Start date:
August 22, 2022
Completion date:
December 2024
Lead sponsor:
Agency:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Agency class:
Industry
Source:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05481645