Clinical trial NCT04157491: Anti-PD-1 Antibody Combined With Anlotinib in the Treatment of Endometrial Cancer
Official title: A Single-center, Single-arm, Phase II Trial to Evaluate the Efficacy and Safety of Anti-PD-1 Antibody Combined With Anlotinib in the Treatment of Recurrent or Advanced Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Endometrial Cancer
Keywords: endometrial cancer
anlotinib
anti PD-1 antibody
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2019-11-08
Enrollment: 23
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the Efficacy and safety of Anti-PD-1 antibody combined With anlotinib in the treatment of recurrent or advanced endometrial cancer.


Eligibility criteria: Inclusion Criteria:

1. ≥18 years of age and female;
2. Histologically confirmed diagnosis of endometrial cancer；
3. Patients must have received at least 1 cycle of platinum-based chemotherapy；

   * Patients with recurrent endometrial cancer that has failed at least one line of platinum-based system chemotherapy
   * Patients with newly diagnosed advanced endometrial cancer has persist lesion after standard treatment with surgery and chemotherapy ± radiotherapy （at least one line of platinum-based systemic chemotherapy）
4. At least one measurable lesion according to RECIST1.1 on CT;
5. ECOG performance status 0-2;
6. Life expectancy ≥ 3 months;
7. Adequate hepatic, renal, heart, and hematologic functions. Absolute Neutrophil Count(ANC) ≥ 1.5×109/L, Platelet (PLT) ≥ 70×109/L, Hemoglobin(HGB) ≥ 80 g/L, total bilirubin within 1.5×the upper limit of normal (ULN), and serum transaminase≤2.5×Upper Limit Of Normal(ULN), serum creatine ≤ 1.5 x Upper Limit Of Normal(ULN), creatinine clearance rate ≥50ml/min, International Normalized Ratio\<1.5 x Upper Limit Of Normal(ULN), Urinary protein≤（+）and Thyroid stimulating hormone≤ 1.5 x Upper Limit Of Normal(ULN).
8. Signed and dated informed consent.

Exclusion Criteria:

1. Pathology confirmed with sarcoma components (including malignant mixed mullerian tumors, endometrial leiomyosarcoma, and endometrial stromal sarcoma);
2. Exposured to any anti-tumor drugs within 4 weeks;
3. Less than 4 weeks since the patient underwent any major surgery or expect a major surgery during trial;
4. Radiation therapy within 21 days（Palliative radiotherapy for bone metastases within14 days）;
5. Exposured to any anti-PD1 antibody drugs；
6. Any unresolved toxicity CTCAE \> Grade 1 from the prior chemoradiation therapy（Excluding hair loss and neurotoxicity）;
7. Current or prior use of any immunosuppressive medication or systemic hormone therapy（which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid Prednisone\>10mg/d）within 14 days before the first dose of anti-PD1 antibody and Anlotinib；
8. Any primary malignancy within 5 years (except for fully treated in situ malignant such as breast cancer, bladder cancer, cervical carcinoma in situ, cutaneous basal cell carcinoma or squamous cell carcinoma);
9. History of psychiatric drugs abuse and not be abstinent, or dysphrenia；
10. Central nervous system diseases, including uncontrollable epilepsy and symptomatic brain metastases;
11. Digestive diseases that may affect drug absorption (such as atrophic gastritis)
12. Active ulcers, intestinal perforation, intractable intestinal obstruction, and history of digestive tract perforation within 28 days prior to enrollment；
13. Uncontrolled hypertension（blood pressure \>140/90 mmHg after adequate treatment）;
14. Severe cardiovascular disease: unstable angina pectoris, myocardial infarction, grade III-IV cardiac insufficiency (NYHA standard), and peripheral vascular disease above 2 degrees within 6 months prior to enrollment;
15. Severe arrhythmia requiring drug control, QT interval \>470ms；
16. Active hemorrhage or hemorrhage tendency.
17. Within 6 months before the first treatment occurs artery / venous thromboembolic events, such as cerebral vascular accident (including transient ischemic attack (TIA), hematencephalon, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.
18. Active infections such as HIV/AIDS or other serious infectious diseases
19. Any active autoimmune disease or history of autoimmune disease (including but not limit to autoimmune hepatitis, interstitial pneumonia, hepatitis, enteritis, nephritis, hyperthyroidism, pituitary inflammation, vasculitis, uveitis) . Patients need receiving systemic hormonal therapy and/or immunosuppressive therapy (eg asthma requiring bronchodilators);
20. Receipt of live attenuated vaccination within 30 days prior to study entry;
21. Known to be allergic to any drug in the study;
22. For women of child-bearing age, the pregnancy test results (serum or urine) within 7 days before enrolment must be negative. They will take appropriate methods for contraception during the study.
23. Other conditions regimented at investigators' discretion.

Primary outcomes:
measure: Objective Response Rate(ORR)
timeFrame: Approximately 24 months.
Secondary outcomes:
measure: Duration of Response(DoR)
timeFrame: Approximately 24 months.
measure: Disease Control Rate(DCR)
timeFrame: Approximately 24 months.
measure: Time to Objective Response(TTR)
timeFrame: Approximately 24 months.
measure: Progression Free Survival(PFS)
timeFrame: Approximately 24 months.
measure: Overall Survival（OS）
timeFrame: Approximately 48 months.
measure: Overall Survival Rate at 12 months
timeFrame: Approximately 12 months.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Centre
state: Guangdong
Study officials:
References:
citation: Wei W, Ban X, Yang F, Li J, Cheng X, Zhang R, Huang X, Huang Y, Li Q, Qiu Y, Zheng M, Zhu X, Li J. Phase II trial of efficacy, safety and biomarker analysis of sintilimab plus anlotinib for patients with recurrent or advanced endometrial cancer. J Immunother Cancer. 2022 May;10(5):e004338. doi: 10.1136/jitc-2021-004338.