Bevacizumab After Chemoradiotherapy For Locally Advanced Lung Adenocarcinoma

Study Overview
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Brief Summary
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This prospective phase II study is to determine the efficacy and safety of bevacizumab maintenance therapy after concurrent chemoradiotherapy in locally advanced lung adenocarcinoma

Detailed Description
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This prospective phase II study is to determine the efficacy and safety of bevacizumab maintenance therapy after concurrent chemoradiotherapy in locally advanced lung adenocarcinoma. All patients received 4 cycles of weekly docetaxel (25mg/㎡) and nedaplatin (25mg/㎡)(DP), each of 1 day's duration, combined with split-course thoracic radiotherapy, with one-month break.Bevacizumab maintenance therapy starts 1-2 months later after the chemotherapy.The recommended dose for intravenous infusion is 15mg/kg body weight, and the drug is given every 3 weeks for up to 1 year. Toxicities will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0.

Official Title
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A Single-armed Phase Ⅱ Study of Bevacizumab Maintenance Therapy After Chemoradiotherapy for Locally Advanced Lung Adenocarcinoma

Conditions
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Lung Adenocarcinoma

Intervention / Treatment
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* Drug: Bevacizumab
* Radiation: chest radiation
* Drug: concurrent chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic confirmation of lung adenocarcinoma Patients have measurable or evaluable lesions based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Unresectable, refusing surgery or after R2 surgery ,confirmed by PET-CT or chest and abdominal CT, craniocerebral MRI, and ECT. After radiotherapy and chemotherapy, the tumor is in partial remission, complete remission or stable. 1-2 months after chemoradiotherapy ends. Organ and bone marrow functions were normal within the first 30 days of enrollment, including: • AST, ALT≤ 2.5*ULN or ≤5*ULN (with liver metastasis); • TBil ≤ 1.5 ULN • neutrophils absolute value ≥500 cells/mm3 • creatinine clearance ≥45 mL/min ;• platelets≥50,000 cells/mm3. CB6 within normal limits Patients and their family signed the informed consents Exclusion Criteria: Lung squamous carcinoma. The tumor has completely approached, encircled, or invaded the intravascular space of the great vessels (e.g., the pulmonary artery or the superior vena cava). The tumor was associated with a cavity over 2cm in diameter. Bleeding tendency or coagulation disorder. Patients with hemoptysis (1/2 teaspoon blood/day) within 1 month. Full-dose anticoagulation therapy was used within the past 1 month. Severe vascular disease occurred within 6 months. Gastrointestinal fistula, perforation or abdominal abscess occurred within 6 months. Hypertensive crisis, hypertensive encephalopathy, symptomatic heart failure (New York class II or above), active cerebrovascular disease or cardiovascular disease occurred within 6 months. Uncontrolled hypertension (systolic > 150mmHg and/or diastolic > 100mmHg). Major surgery within 28 days or minor surgery or needle biopsy within 48 hours. Urine protein 3-4+, or 24h urine protein quantitative >1g. Degree 3 esophagitis after chemoradiotherapy has not recovered. Elderly patients (age 75 years). The investigator does not consider the participant to be eligible for this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab<br>All patients received four cycles of weekly docetaxel (25mg/㎡) and nedaplatin (25mg/㎡)(DP), each of 1 day's duration, combined with split-course thoracic radiotherapy, with one-month break.Then every patients are treated with Bevacizumab 1-2 months later.The recommended dose for intravenous infusion is 15mg/kg body weight, which is given every 3 weeks for up to 1 year. | Drug: Bevacizumab<br>* Patients are treated with Bevacizumab 1-2 months after the chemoradiotherapy.The recommended dose for intravenous infusion is 15mg/kg body weight, which is given every 3 weeks for up to 1 year.<br>Radiation: chest radiation<br>* split-course chest radiation<br>Drug: concurrent chemotherapy<br>* weekly docetaxel(25mg/㎡) and nedaplatin(25mg/㎡) concurrent with chest radiation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival in patients | 3-year | 
| rate of grade≥2 radiation pneumonia(NCI-CTC4.0) | radiation-induced pulmonary injury is classified into 1-5 grades according to NCI-CTC4.0. The incidence of symptomatic radiation-induced pulmonary injury: the ratio of grade 2 and above radiation-induced pulmonary injury cases in 1 year after radio therapy to all cases can be evaluated . | 1 year from the end of chemoradiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | overall survival | 3-year | 
| response rate |  | 3-year | 
| rate of grade 3-4 radiation esophagitis |  | 3-year | 
| rate of grade 3-4 radiation pneumonitis |  | 3-year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bevacizumab, Split-course Chemoradiotherapy