Study of Anlotinib Plus Sintilimab in the Treatment of Advanced Esophageal Squamous Cell Carcinoma
Primary Purpose
Esophageal Squamous Cell Carcinoma
Status
Unknown status
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Anlotinib + Sintilimab
Sponsored by
About this trial
This is an interventional treatment trial for Esophageal Squamous Cell Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Pathologically (histologically or cytologically) confirmed diagnosis of esophageal squamous cell carcinoma (excluding mixed type adenosquamous carcinoma )
- Patients undergoing first-line systemic chemotherapy (which may include taxanes, platinum and fluorouracil) progression. For radical concurrent chemoradiotherapy, neoadjuvant/adjuvant therapy (chemotherapy or chemoradiotherapy), if disease progression occurs during treatment or within 6 months after stopping treatment, Count it as a first-line treatment failure.(Note: Patients with advanced or relapsed non target lesions who progress again after radiotherapy alone are included. Palliative treatment for local lesions (non target lesions) lasted for more than 2 weeks.)
- At least one measurable/evaluable lesion by RECIST v1.1(Cavity organ such as esophagus can not be used as measurable lesions). And the measurable lesions should not have received local treatment such as radiotherapy (The lesion located in the previous radiotherapy area, if confirmed to progress, and meets the RECIST 1.1 standard, can also be used as a target lesion).
- 18~80 years, both men and women.
- Patients who can provide histological specimens for pathological review.
- Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1.
- Life expectancy of ≥ 12 weeks.
The main organs function normally, that is, the following criteria are met:
(1) Blood routine examination:
- HB≥90g/L;
- ANC ≥ 1.5 × 109 / L;
PLT ≥ 80 × 109 / L. (2) Biochemical examination:
- TBIL ≤ 1.5ULN
- ALT and AST ≤ 2.5ULN
- plasma Cr ≤ 1.5ULN or creatinine clearance (CCr) ≥ 60ml / min
- left ventricular ejection fraction (LVEF)≥ normal low limit (50%)
- Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device,contraceptive and condom) throughout treatment and for at least 6 months after study is stopped;the result of serum or urine pregnancy test should be negative before enrollment;Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped.
- Patients should participate in the study voluntarily and sign informed consent.
Exclusion Criteria:
- The patients who had or were suffering from other malignant tumors within 5 years, except for the cured cervical carcinoma in situ, non melanoma skin cancer and superficial bladder tumor [ta (non-invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)] and those who developed rapidly within 3 months.
- Patients with a history of perforation and / or fistula within 6 months before the first medication.
- Patients with a high risk of bleeding or perforation due to the apparent invasion of adjacent organs (aorta or trachea) of the esophageal lesion, or patients who have formed fistulas.
Have received any of the following treatments:
- Patients who received Sindilimab therapy or other immunotherapy against PD-1/PD-L1.
- Patients who have participated in other drug clinical trials within four weeks.
- Enter another clinical study, unless it is an observational (non intervention) clinical study or an intervention clinical study.
- Receive the last dose of anticancer treatment (including radiotherapy, etc.) within ≤ 4 weeks before the first use of the study drug.
- The patient is using immunosuppressive agents or systemic hormonal therapy for immunosuppression purposes (dose >10 mg/day of prednisone ) and continues to be used within 2 weeks prior to enrollment, except for the use of corticosteroids for local esophageal inflammation and prevention of allergy, nausea and vomiting. In the absence of active autoimmune diseases, inhaled or topical corticosteroids and corticosteroid replacement with a therapeutic dose of prednisone greater than 10 mg / day are permitted.
- Patients who had been vaccinated with anti-tumor vaccine or had been vaccinated with live vaccine within 4 weeks before the first administration of the study drug.
- The patient had major surgery or severe trauma within 4 weeks before the first use of the study drug.
- A history of immunodeficiency, including a positive HIV test or other acquired, congenital immunodeficiency disease, or a history of organ transplantation.
- The toxicity of previous anti-tumor therapy did not return to ≤ NCI CTC AE v5.01 (except alopecia) or the level specified in the inclusion / exclusion criteria.
- Allergic to monoclonal antibody and anlotinib
- Patients with significant malnutrition. If the patient is receiving intravenous infusion of nutrient solution or requires hospitalization for continuous infusion treatment, then exclusion. Before randomization, patients with good nutrition control for more than 28 days can be enrolled.
Patients with any severe and / or uncontrolled disease, include:
- Patients with hypertension who can not be well controlled by antihypertensive drugs (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg).
- With myocardial ischemia or myocardial infarction, arrhythmia (including QTc ≥ 480ms) and ≥ 2 congestive heart failure (NYHA classification).
- Serious or uncontrolled disease or active infection (≥ NCI CTC AE V5.02 infection), which the researchers believe will increase the risk related to research participation, drug delivery or affect the ability of subjects to receive the study drug.
- Renal failure requires hemodialysis or peritoneal dialysis.
- Poor glycemic control in diabetic patients (FBG > 10mmol / L).
- Routine urine showed that urinary protein was ≥ 2+ and 24-hour urinary protein was confirmed to be more than 1.0g.
- Patients with epilepsy and need treatment.
- 4 weeks before of enrollment; any sites of bleeding NCI CTC AE grade ≥3, such as unhealed wounds, ulcers or fractures.
- Patients with arteriovenous thrombosis events within 3 months, such as cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism;
- The patient has any active autoimmune disease (such as the following, but not limited to: Interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adult, autoimmune hypothyroidism treated with stable dose of thyroid replacement hormone and type I diabetes treated with stable dose of insulin.
- The patient has a history of interstitial lung disease (except radiation pneumonia without hormone therapy) and non infectious pneumonia.
- Patients with active pulmonary tuberculosis infection found by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within one year before enrollment, or with a history of active pulmonary tuberculosis infection more than one year ago but without regular treatment;
- Patients with active hepatitis B (HBV-DNA ≥ 104 copy number / ml or 2000 IU / ml) Or hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher than the lower limit of detection of the analytical method).
- According to the judgment of the researcher, there are other factors that may cause the subject to be forced to terminate the study, such as suffering from other serious diseases (including mental illness) requiring combined treatment, serious laboratory abnormalities, family or social factors, which may affect the safety of the subject or the collection of experimental data
- Symptomatic central nervous system metastasis and/or cancerous meningitis are known to exist.
- Pregnant or lactating women.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Anlotinib + Sintilimab
Arm Description
Outcomes
Primary Outcome Measures
Overall survival(OS)
From date of randomization until the date of death from any cause
Secondary Outcome Measures
Progress free survival (PFS)
From date of randomization until the date of first documented progression or date of death from any cause
Objective Response Rate (ORR)
From date of randomization until the date of death from any cause
Disease Control Rate (DCR)
Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD)
Full Information
NCT ID
NCT04813406
First Posted
March 21, 2021
Last Updated
March 21, 2021
Sponsor
Henan Provincial People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04813406
Brief Title
Study of Anlotinib Plus Sintilimab in the Treatment of Advanced Esophageal Squamous Cell Carcinoma
Official Title
Anlotinib in Combination With Sintilimab as Second-line Treatment for Advanced Esophageal Squamous Cell Carcinoma (ESCC) : a Multicenter, Single-arm, Open-label Phase Ⅱ Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Unknown status
Study Start Date
March 2021 (Anticipated)
Primary Completion Date
January 2022 (Anticipated)
Study Completion Date
January 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Henan Provincial People's Hospital
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to observe and evaluate the efficacy and safety of anlotinib combined with sindilimab as second-line treatment for advanced esophageal squamous cell carcinoma (ESCC). In addition, we also explored the possible mechanism of anlotinib combined with sindilimab in order to screen out biomarkers that can predict the efficacy of the combination therapy.
Detailed Description
China is one of the regions with the highest risk of esophageal cancer in the world, and more than 90% of esophageal cancer is squamous cell carcinoma (SCC). The incidence of esophageal cancer is ranked sixth and the mortality rate ranks fourth in China. At present, the first-line treatment of advanced esophageal cancer is mainly based on the combination of paclitaxel, cisplatin and fluorouracil. After the failure of first-line treatment, there is no standard second-line treatment. The investigators designed a multicenter, single-arm, open-label phase Ⅱ clinical trial of anlotinib combined with sindilimab as second-line treatment for advanced esophageal squamous cell carcinoma (ESCC).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Esophageal Squamous Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
53 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Anlotinib + Sintilimab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Anlotinib + Sintilimab
Intervention Description
Anlotinib: 1 capsule (10mg) once a day, d1-d14 per cycle, 3 weeks for a treatment cycle.
Sintilimab: 200 mg/time, intravenous injection, every 3 weeks is one cycle.
Primary Outcome Measure Information:
Title
Overall survival(OS)
Description
From date of randomization until the date of death from any cause
Time Frame
up to 2 year
Secondary Outcome Measure Information:
Title
Progress free survival (PFS)
Description
From date of randomization until the date of first documented progression or date of death from any cause
Time Frame
up to 2 year
Title
Objective Response Rate (ORR)
Description
From date of randomization until the date of death from any cause
Time Frame
up to 1 year
Title
Disease Control Rate (DCR)
Description
Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD)
Time Frame
up to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathologically (histologically or cytologically) confirmed diagnosis of esophageal squamous cell carcinoma (excluding mixed type adenosquamous carcinoma )
Patients undergoing first-line systemic chemotherapy (which may include taxanes, platinum and fluorouracil) progression. For radical concurrent chemoradiotherapy, neoadjuvant/adjuvant therapy (chemotherapy or chemoradiotherapy), if disease progression occurs during treatment or within 6 months after stopping treatment, Count it as a first-line treatment failure.(Note: Patients with advanced or relapsed non target lesions who progress again after radiotherapy alone are included. Palliative treatment for local lesions (non target lesions) lasted for more than 2 weeks.)
At least one measurable/evaluable lesion by RECIST v1.1(Cavity organ such as esophagus can not be used as measurable lesions). And the measurable lesions should not have received local treatment such as radiotherapy (The lesion located in the previous radiotherapy area, if confirmed to progress, and meets the RECIST 1.1 standard, can also be used as a target lesion).
18~80 years, both men and women.
Patients who can provide histological specimens for pathological review.
Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1.
Life expectancy of ≥ 12 weeks.
The main organs function normally, that is, the following criteria are met:
(1) Blood routine examination:
HB≥90g/L;
ANC ≥ 1.5 × 109 / L;
PLT ≥ 80 × 109 / L. (2) Biochemical examination:
TBIL ≤ 1.5ULN
ALT and AST ≤ 2.5ULN
plasma Cr ≤ 1.5ULN or creatinine clearance (CCr) ≥ 60ml / min
left ventricular ejection fraction (LVEF)≥ normal low limit (50%)
Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device,contraceptive and condom) throughout treatment and for at least 6 months after study is stopped;the result of serum or urine pregnancy test should be negative before enrollment;Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped.
Patients should participate in the study voluntarily and sign informed consent.
Exclusion Criteria:
The patients who had or were suffering from other malignant tumors within 5 years, except for the cured cervical carcinoma in situ, non melanoma skin cancer and superficial bladder tumor [ta (non-invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)] and those who developed rapidly within 3 months.
Patients with a history of perforation and / or fistula within 6 months before the first medication.
Patients with a high risk of bleeding or perforation due to the apparent invasion of adjacent organs (aorta or trachea) of the esophageal lesion, or patients who have formed fistulas.
Have received any of the following treatments:
Patients who received Sindilimab therapy or other immunotherapy against PD-1/PD-L1.
Patients who have participated in other drug clinical trials within four weeks.
Enter another clinical study, unless it is an observational (non intervention) clinical study or an intervention clinical study.
Receive the last dose of anticancer treatment (including radiotherapy, etc.) within ≤ 4 weeks before the first use of the study drug.
The patient is using immunosuppressive agents or systemic hormonal therapy for immunosuppression purposes (dose >10 mg/day of prednisone ) and continues to be used within 2 weeks prior to enrollment, except for the use of corticosteroids for local esophageal inflammation and prevention of allergy, nausea and vomiting. In the absence of active autoimmune diseases, inhaled or topical corticosteroids and corticosteroid replacement with a therapeutic dose of prednisone greater than 10 mg / day are permitted.
Patients who had been vaccinated with anti-tumor vaccine or had been vaccinated with live vaccine within 4 weeks before the first administration of the study drug.
The patient had major surgery or severe trauma within 4 weeks before the first use of the study drug.
A history of immunodeficiency, including a positive HIV test or other acquired, congenital immunodeficiency disease, or a history of organ transplantation.
The toxicity of previous anti-tumor therapy did not return to ≤ NCI CTC AE v5.01 (except alopecia) or the level specified in the inclusion / exclusion criteria.
Allergic to monoclonal antibody and anlotinib
Patients with significant malnutrition. If the patient is receiving intravenous infusion of nutrient solution or requires hospitalization for continuous infusion treatment, then exclusion. Before randomization, patients with good nutrition control for more than 28 days can be enrolled.
Patients with any severe and / or uncontrolled disease, include:
Patients with hypertension who can not be well controlled by antihypertensive drugs (systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 100 mmHg).
With myocardial ischemia or myocardial infarction, arrhythmia (including QTc ≥ 480ms) and ≥ 2 congestive heart failure (NYHA classification).
Serious or uncontrolled disease or active infection (≥ NCI CTC AE V5.02 infection), which the researchers believe will increase the risk related to research participation, drug delivery or affect the ability of subjects to receive the study drug.
Renal failure requires hemodialysis or peritoneal dialysis.
Poor glycemic control in diabetic patients (FBG > 10mmol / L).
Routine urine showed that urinary protein was ≥ 2+ and 24-hour urinary protein was confirmed to be more than 1.0g.
Patients with epilepsy and need treatment.
4 weeks before of enrollment; any sites of bleeding NCI CTC AE grade ≥3, such as unhealed wounds, ulcers or fractures.
Patients with arteriovenous thrombosis events within 3 months, such as cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism;
The patient has any active autoimmune disease (such as the following, but not limited to: Interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adult, autoimmune hypothyroidism treated with stable dose of thyroid replacement hormone and type I diabetes treated with stable dose of insulin.
The patient has a history of interstitial lung disease (except radiation pneumonia without hormone therapy) and non infectious pneumonia.
Patients with active pulmonary tuberculosis infection found by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within one year before enrollment, or with a history of active pulmonary tuberculosis infection more than one year ago but without regular treatment;
Patients with active hepatitis B (HBV-DNA ≥ 104 copy number / ml or 2000 IU / ml) Or hepatitis C (positive hepatitis C antibody, and HCV-RNA is higher than the lower limit of detection of the analytical method).
According to the judgment of the researcher, there are other factors that may cause the subject to be forced to terminate the study, such as suffering from other serious diseases (including mental illness) requiring combined treatment, serious laboratory abnormalities, family or social factors, which may affect the safety of the subject or the collection of experimental data
Symptomatic central nervous system metastasis and/or cancerous meningitis are known to exist.
Pregnant or lactating women.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianwei Zhou, Doctor
Phone
0086-13937120756
Email
drzhoujw@126.com
12. IPD Sharing Statement
Learn more about this trial
Study of Anlotinib Plus Sintilimab in the Treatment of Advanced Esophageal Squamous Cell Carcinoma
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