Anti-PD-1 Antibody Combined With Anlotinib in the Treatment of Endometrial Cancer

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

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.

Study Overview

• Status: Recruiting
• Conditions: Endometrial Cancer
• Intervention / Treatment: Drug: anlotinib and anti PD-1 antibody

• Study Type: Interventional
• Enrollment (Anticipated): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-Sen University Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anlotinib and anti PD-1 antibody	Drug: anlotinib and anti PD-1 antibody; Anti-PD-1 antibody administered by intravenous (IV) infusion on Day 1 of each 21-day cycle plus Anlotinib 12 mg administered orally (PO) once daily (QD) Day1-Day14 during each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate(ORR)	Objective tumor response was defined as the proportion of patients whose tumor volume has been reduced to a predetermined value and can be maintained for more than 4 weeks, ie ORR=CR+PR.	Approximately 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response(DoR)	Duration of response was defined as the time when the tumor is first evaluated as CR or PR to the first assessment for PD or for any cause of death.	Approximately 24 months.
Disease Control Rate(DCR)	Disease control rate was defined as the proportion of subjects with complete response (CR) or partial response (PR) or disease stabilization (SD) in the analyzed population according to the RECIST 1.1 criteria.	Approximately 24 months.
Time to Objective Response(TTR)	Time to objective response was defined as the time from the start of treatment to the first objective tumor remission (CR or PR).	Approximately 24 months.
Progression Free Survival(PFS)	Progression-free survival was defined as the duration of time from study entry to time of progression, death, or the date of last contact, whichever occurs first.	Approximately 24 months.
Overall Survival（OS）	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.	Approximately 48 months.
Overall Survival Rate at 12 months	Overall survival rate at 12 months was defined as the proportion of patients who were still alive in 12 months.	Approximately 12 months.

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Publications and helpful links

General Publications

• 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). pii: e004338. doi: 10.1136/jitc-2021-004338.

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2019
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 6, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): November 8, 2019
• Last Update Submitted That Met QC Criteria: November 6, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: endometrial cancer; anlotinib; anti PD-1 antibody
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies
• Other Study ID Numbers: SINAL1618

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