Bevacizumab After Chemoradiotherapy For Locally Advanced Lung Adenocarcinoma

Phase 2

Completed

Interventions: Drug: Bevacizumab
Radiation: chest radiation
Drug: concurrent chemotherapy

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Bevacizumab	chest radiation	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.
Bevacizumab	concurrent chemotherapy	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.
Bevacizumab	Bevacizumab	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.

Primary Outcome Measures

Name	Time	Method
Progression-free survival	3-year	Progression-free survival in patients
rate of grade≥2 radiation pneumonia(NCI-CTC4.0)	1 year from the end of chemoradiotherapy	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 .

Secondary Outcome Measures

Name	Time	Method
response rate	3-year
rate of grade 3-4 radiation esophagitis	3-year
rate of grade 3-4 radiation pneumonitis	3-year
overall survival	3-year	overall survival

Locations (1): Sun yat-sen University Cancer Center
🇨🇳
Guangzhou, Guangdong, China