Back to resultsSintilimab Combined With Anlotinib Therapy for Initially Unresectable Non-small Cell Lung Cancer
Primary Purpose
Carcinoma, Non-Small-Cell Lung
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Sintilimab
Anlotinib
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring Non-small-cell lung cancer, Sintilimab, Anlotinib
Eligibility Criteria
Inclusion Criteria:
- According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients with locally advanced (stage II-III C) NSCLC confirmed by histology who are initially unable to undergo surgery and concomitant radiochemotherapy and are confirmed to have at least one measurable lesion according to RECIST 1.1.
- Age ≥18 years and ≤75 years.
- ECOG PS score: 0 to 1.
The main organs function is normal, that is, the following criteria met:
- Good hematopoietic function, defined as absolute neutrophil count ≥1.5×109 /L, platelet count≥100 ×109 /L, hemoglobin ≥90g/L [no blood transfusion or no erythropoietin (EPO) dependence within 7 days before enrollment];
- Biochemical test results should meet the following criteria: BIL < 1.25 times the upper limit of normal value (ULN); ALT and AST < 2.5 × ULN; in case of liver metastases, ALT and AST < 5 × ULN; Cr ≤1.5×ULN or creatinine clearance (CCr) ≥60ml/min; Coagulation function is good, INR and PT ≤1.5 × ULN;
- The oxygen saturation of the finger tip ≥ 92% both at rest and during walking (without oxygen inhalation).
- The life expectancy ≥12 weeks.
- Signed and dated informed consent.
Exclusion Criteria:
- Subjects at risk of massive hemoptysis or with blood in sputum, including but not limited to tumor lesions no more than 5 mm away from large vessels, tumors invading large vessels, and obvious lung cavity/necrotizing tumors.
- Small cell lung cancer (including mixed small cell and non-small cell lung cancer) or central squamous cell carcinoma.
- With driver mutation (EGFR/ALK/ROS1).
- With uncontrollable hypertension (systolic pressure > 160 mmHg, diastolic pressure > 100 mmHg) even receiving antihypertensive drug therapy.
- Has an active autoimmune disease, history of allogeneic stem cell transplantation or organ transplantation that has required systemic treatment. Replacement therapy is not considered a form of systemic treatment and is allowed.
- Has an active infection requiring systemic therapy.
- Has other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.) or concomitant diseases that seriously endanger the patients or affect the patients completing the study at the same time.
- With immunodeficiency status, including but not limited to HIV infection and primary immunodeficiency diseases.
- Previously treated with ICIs.
- Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental arm
Arm Description
Sintilimab will be given intravenously at a dose of 200mg every 21 days. Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle. Tumor evaluation will be conducted after treatment of the tested regimen every 2 cycles. Subsequent treatment will be determined based on the evaluation results: If the patients are not suitable for radical surgery, but the result of efficacy evaluation is CR, PR, or SD, they can continue to receive the tested regimen. If the patients are still not suitable for radical surgery after 6 cycles of the tested regimen, the standard first-line or immunotherapy after chemoradiotherapy or radiotherapy will be given. If patients are eligible for radical surgery, surgery will be performed within 4 weeks after completion of the last tested regimen.
Outcomes
Primary Outcome Measures
Surgical conversion rate
The surgical conversion rate was defined as the proportion of subjects with the successful conversion over all subjects who received the tested regime.
Secondary Outcome Measures
Objective response rate (ORR)
ORR is defined as the percentage of participants who have the best overall response (BOR) of complete response (CR) or partial response (PR) assessed based on RECIST 1.1.
R0 resection rate
R0 resection rate is defined as the complete resection rate of all tumor under microscope.
Major pathological response rate
Major pathological response rate is defined as the percentage of patients who achieved a major pathological response (residual tumor ≤10%).
Pathological complete response rate
Pathological complete response rate is defined as the percentage of patients who achieved a pathological complete response (residual tumor = 0%).
Overall survival (OS)
OS is measured from the time from the treatment onset (date of first study dose) until the date of death from any cause.
Progression-free survival (PFS)
PFS is measured from the time from the treatment onset (date of first study dose) until the date of tumor progression or death from any cause.
Disease-free survival (DFS)
DFS is measured from the time from radical surgery until the date of tumor progression or death from any cause.
Treatment-related adverse events
Incidence and grade of treatment-related adverse events assessed based on CTCAE 5.0
Full Information
NCT ID
NCT05306847
First Posted
March 21, 2022
Last Updated
March 23, 2022
Sponsor
Peking Union Medical College Hospital
Collaborators
Xinda Biopharmaceutical Group, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05306847
Brief Title
Sintilimab Combined With Anlotinib Therapy for Initially Unresectable Non-small Cell Lung Cancer
Official Title
Sintilimab Combined With Anlotinib Therapy for Patients With Initially Unresectable Stage II-III Non-small Cell Lung Cancer: A Prospective, Single-arm Study
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2022 (Anticipated)
Primary Completion Date
April 1, 2024 (Anticipated)
Study Completion Date
April 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking Union Medical College Hospital
Collaborators
Xinda Biopharmaceutical Group, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Concurrent or sequential chemoradiotherapy has been recommended as the standard treatment for locally advanced and unresectable non-small cell lung cancer (NSCLC). However, its efficacy remains to be improved. PD-1/PD-L1 inhibitors have been proven to be effective for late-stage NSCLC, and anti-angiogenesis agents have also been used for the first-line treatment of advanced or metastatic NSCLC. Therefore, we designed this single-arm clinical trial, which aims to investigate the safety and feasibility of sintilimab combined with anlotinib therapy for patients with initially unresectable stage II-III NSCLC.
Detailed Description
Concurrent or sequential chemoradiotherapy is the standard treatment for patients with locally advanced NSCLC, but patients receiving chemoradiotherapy have limited improvement in prognosis and are almost impossible to achieve a radical cure. Considering the excellent effect of immunotherapy and anti-angiogenesis therapy in NSCLC, we designed this single-arm clinical study, which aims to investigate the safety and feasibility of sintilimab combined with anlotinib therapy for patients with initially unresectable stage II-III NSCLC, in order to enable patients to achieve further surgical treatment and prolonged survival.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung
Keywords
Non-small-cell lung cancer, Sintilimab, Anlotinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
93 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental arm
Arm Type
Experimental
Arm Description
Sintilimab will be given intravenously at a dose of 200mg every 21 days. Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle.
Tumor evaluation will be conducted after treatment of the tested regimen every 2 cycles. Subsequent treatment will be determined based on the evaluation results: If the patients are not suitable for radical surgery, but the result of efficacy evaluation is CR, PR, or SD, they can continue to receive the tested regimen. If the patients are still not suitable for radical surgery after 6 cycles of the tested regimen, the standard first-line or immunotherapy after chemoradiotherapy or radiotherapy will be given. If patients are eligible for radical surgery, surgery will be performed within 4 weeks after completion of the last tested regimen.
Intervention Type
Drug
Intervention Name(s)
Sintilimab
Other Intervention Name(s)
IBI308, Tyvyt
Intervention Description
Sintilimab will be given intravenously at a dose of 200mg every 21 days.
Intervention Type
Drug
Intervention Name(s)
Anlotinib
Other Intervention Name(s)
Anlotinib hydrochloride, AL3818
Intervention Description
Anlotinib will be given at a dose of 12mg once daily on days 1-14 of a 21-day cycle.
Primary Outcome Measure Information:
Title
Surgical conversion rate
Description
The surgical conversion rate was defined as the proportion of subjects with the successful conversion over all subjects who received the tested regime.
Time Frame
18 weeks from the initiation of the tested regime therapy
Secondary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
ORR is defined as the percentage of participants who have the best overall response (BOR) of complete response (CR) or partial response (PR) assessed based on RECIST 1.1.
Time Frame
18 weeks from the initiation of the tested regime therapy
Title
R0 resection rate
Description
R0 resection rate is defined as the complete resection rate of all tumor under microscope.
Time Frame
within 28 working days after operation
Title
Major pathological response rate
Description
Major pathological response rate is defined as the percentage of patients who achieved a major pathological response (residual tumor ≤10%).
Time Frame
within 28 working days after operation
Title
Pathological complete response rate
Description
Pathological complete response rate is defined as the percentage of patients who achieved a pathological complete response (residual tumor = 0%).
Time Frame
within 28 working days after operation
Title
Overall survival (OS)
Description
OS is measured from the time from the treatment onset (date of first study dose) until the date of death from any cause.
Time Frame
2 years from the initiation of the tested regime therapy
Title
Progression-free survival (PFS)
Description
PFS is measured from the time from the treatment onset (date of first study dose) until the date of tumor progression or death from any cause.
Time Frame
2 years from the initiation of the tested regime therapy
Title
Disease-free survival (DFS)
Description
DFS is measured from the time from radical surgery until the date of tumor progression or death from any cause.
Time Frame
2 years from the initiation of the tested regime therapy
Title
Treatment-related adverse events
Description
Incidence and grade of treatment-related adverse events assessed based on CTCAE 5.0
Time Frame
3 months from the end of the tested regime therapy
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients with locally advanced (stage II-III C) NSCLC confirmed by histology who are initially unable to undergo surgery and concomitant radiochemotherapy and are confirmed to have at least one measurable lesion according to RECIST 1.1.
Age ≥18 years and ≤75 years.
ECOG PS score: 0 to 1.
The main organs function is normal, that is, the following criteria met:
Good hematopoietic function, defined as absolute neutrophil count ≥1.5×109 /L, platelet count≥100 ×109 /L, hemoglobin ≥90g/L [no blood transfusion or no erythropoietin (EPO) dependence within 7 days before enrollment];
Biochemical test results should meet the following criteria: BIL < 1.25 times the upper limit of normal value (ULN); ALT and AST < 2.5 × ULN; in case of liver metastases, ALT and AST < 5 × ULN; Cr ≤1.5×ULN or creatinine clearance (CCr) ≥60ml/min; Coagulation function is good, INR and PT ≤1.5 × ULN;
The oxygen saturation of the finger tip ≥ 92% both at rest and during walking (without oxygen inhalation).
The life expectancy ≥12 weeks.
Signed and dated informed consent.
Exclusion Criteria:
Subjects at risk of massive hemoptysis or with blood in sputum, including but not limited to tumor lesions no more than 5 mm away from large vessels, tumors invading large vessels, and obvious lung cavity/necrotizing tumors.
Small cell lung cancer (including mixed small cell and non-small cell lung cancer) or central squamous cell carcinoma.
With driver mutation (EGFR/ALK/ROS1).
With uncontrollable hypertension (systolic pressure > 160 mmHg, diastolic pressure > 100 mmHg) even receiving antihypertensive drug therapy.
Has an active autoimmune disease, history of allogeneic stem cell transplantation or organ transplantation that has required systemic treatment. Replacement therapy is not considered a form of systemic treatment and is allowed.
Has an active infection requiring systemic therapy.
Has other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.) or concomitant diseases that seriously endanger the patients or affect the patients completing the study at the same time.
With immunodeficiency status, including but not limited to HIV infection and primary immunodeficiency diseases.
Previously treated with ICIs.
Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yingyi Wang, Professor
Phone
+86 010-69158764
Email
wangyingyi@pumch.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chunmei Bai, Professor
Organizational Affiliation
Peking union medical colloge hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified individual participant data for all primary and secondary outcome measures will be made available.
IPD Sharing Time Frame
Data will be available within 1 year of study completion
IPD Sharing Access Criteria
Data access requests will be reviewed by an external independent Review Panel. Requestors will be required to sign a Data Access Agreement
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Sintilimab Combined With Anlotinib Therapy for Initially Unresectable Non-small Cell Lung Cancer
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