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The purpose of this study is to evaluate the tolerability and toxicity of different dose of anlotinib combination with concurrent chemoradiotherapy in the treatment of limited-stage SCLC patients.
Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR1、VEGFR2、VEGFR3、FGFR1/2/3、PDGFRa/β c-Kit and MET. The purpose of this study is to determine the maximum tolerated dose of anlotinib when combination with concurrent chemoradiotherapy. From low dose group up to high dose group, each one had 3 patients at least. Primary group received anlotinib 8mg. The dose of anlotinib would increase gradually until MTD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Concurrent chemoradiotherapy plus anlotinib | Experimental | Concurrent chemoradiotherapy plus anlotinib for 4-6 cycles This study will include a sequential evaluation of 3 subjects per dose group. Low-dose groups: anlotinib 8mg per day with concurrent chemoradiotherapy. Middle-dose groups: anlotinib 10mg per day with concurrent chemoradiotherapy. High-dose groups: anlotinib 12mg per day with concurrent chemoradiotherapy. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Concurrent chemoradiotherapy plus anlotinib | Drug | Anlotinib: for cycle 1-6. P.O; QD; from days 1 to 14 in a 21-day cycle. 8mg in low-dose groups (3 subjects). 10mg in middle-dose groups (3 subjects). 12mg in high-dose groups (3 subjects). Chemotherapy: For cycle 1/4/5/6. Etoposide 100mg/m2, d1-3, q3w; Cisplatin 25mg/m2 d1-3, q3w. For cycle 2/3. Etoposide 50mg/m2, d1-3, q4w; Cisplatin 25mg/m2 d1-3, q4w. Radiotherapy: For cycle 2/3.Thoracic radiotherapy dose will be 2.0Gy per day, given 5 days a week, to cumulative dose of 60~66Gy. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerance Dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DLT reported. | Dose Limiting Toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria | From enrollment to completion of study. Estimated about 18months |
| Measure | Description | Time Frame |
|---|---|---|
| PFS(Progress free survival) | The PFS time is defined as time from enrollment to locoregional or systemic | each 42 days up to intolerance the toxicity or PD (up to 24 months) |
| OS(Overall Survival) |
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Inclusion Criteria:
Exclusion Criteria:
1) Brain metastasis or spinal cord compression 2) Other active malignancies that require simultaneous treatment. 3) History of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease, or history of organ transplantation.
4) History of mental drug abuse and cannot be cured or have mental disorders 6. Patients with any severe and/or uncontrolled disease, including:
8. Patients who received a major surgical treatment or severe trauma, the effects of surgery or trauma have been eliminated in less than 2 weeks before being enrolled 9. Patients with clinically significant hemoptysis occurred within 3 months prior to enrollment (greater than 1/2 teaspoon of bright red blood). History of clinically relevant major bleeding event (e.g. gastrointestinal hemorrhage, hemorrhagic acne, bleeding gastric ulcer, occult blood test ≥ ++, or vasculitis, etc.) 10. Patients who have arterial/venous thromboembolism events within 6 months before being enrolled, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.
11. Coagulation disfunction(INR>1.5 or PT>upper limit of normal(ULN)+4s or activated partial thromboplastin time (APTT) >1.5 upper limit of normal (ULN)), hemorrhagic tendency or receiving the therapy of thrombolysis or anticoagulation.
12. At the discretion of the investigator, the patient may have other factors that may cause the study to be terminated midway.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xiyan Nan, Doctor | Contact | +86 18811796429 | 18811796429@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tianjin Medical University Cancer Institute and Hospital | Recruiting | Tianjin | Tianjin Municipality | 300060 | China |
De-identified individal participant data for all primary and secondary outcome measures will be made available.
Data will be available within 6 months of study completion
Data access requests will be reviewed by an external indepentent Review Panel. Requesdtors will be required to sign a Data Access Agreement.
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| ID | Term |
|---|---|
| D059248 | Chemoradiotherapy |
| C000625192 | anlotinib |
| ID | Term |
|---|---|
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
| D004358 | Drug Therapy |
| D011878 | Radiotherapy |
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OS was defined as time from date of enrollment to date of death due to any cause.
| From enrollment until death (up to 24 months) |
| ORR(Objective Response Rate) | Objective Response Rate (ORR) is defined as participants who had complete response (CR) or partial response(PR) divided by the total number of patients. | each 42 days up to intolerance the toxicity or PD (up to 24 months) |
| DCR(Disease Control Rate) | Disease Control Rate (DCR) defined as the percentage of participants with Disease Control best overall response (complete response, partial response or stable disease). | each 42 days up to intolerance the toxicity or PD (up to 24 months) |