Bevacizumab and Radiotherapy for Oligometastasis of Lung Adenocarcinoma With Negative Driver Gene

Lung Adenocarcinoma Clinical Trial

Official title:

A Single-Armed Phase II Study of Radiation and Bevacizumab Maintenance Therapy for Oligometastasis of Lung Adenocarcinoma With Negative Driver Gene

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03905317
• Other study ID #: GASTO-1047
• Status: Recruiting
• Phase: Phase 2
• Start date: March 1, 2019
• Est. completion date: February 2022

Study information

• Verified date: February 2019
• Source: Sun Yat-sen University
• Contact: Bo Qiu, Attending
• Phone: +86-020-87343031
• Email: qiubo[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This prospective phase II study is determined to explore the efficacy and safety of radiotherapy and bevacizumab maintenance therapy for oligometastatic lung adenocarcinoma with negative driver genes

Description:

This prospective phase II study is determined to explore the efficacy and safety of radiotherapy and bevacizumab maintenance therapy for oligometastatic lung adenocarcinoma with negative driver genes.

The patients receive SBRT radiotherapy for the primary (if any) and metastatic lesions or divided radiotherapy with or without concurrent chemotherapy.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 until disease progression or intolerable toxicity occurs. Toxicities will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: February 2022
• Est. primary completion date: February 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Pathological confirmation of lung adenocarcinoma with negative driver gene including EGFR and ALK.

• Simultaneous oligometastasis, or oligometastasis which occurs after treatment of stage i-iii lung adenocarcinoma (1-5 metastases)

• Oligometasis confirmed by CT, brain MR, bone ECT or PETCT within 30 days before enrollment.

Exclusion Criteria:

• =18 years old

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

• Organ and bone marrow functions are 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.

• Negative pregnancy test 1 week before enrollment for women of childbearing age.

• Patients with concurrent oligostasis should have received at least 4 courses of first-line chemotherapy, and SD or PR should be evaluated after chemotherapy;

• Patients with stage i-iii lung adenocarcinoma with oligo-metastasis after treatment who have previously received systemic chemotherapy (such as concurrent radiotherapy chemotherapy or postoperative adjuvant chemotherapy) are admitted to the group;

• Patients who have received brain radiation therapy due to brain metastasis are admitted to the group.

• The baseline is the exsiting of measurable lesions, and the metastatic lesions are treated with local radiotherapy;The number of metastases defines as:

• - A) two metastatic lesions are identified when bilateral adrenal glands have lesions;

• - B) two consecutive vertebral lesions and paravertebral lesions within 6cm can be considered as one metastatic lesion, and the lesions of non-continuous vertebral body should be counted separately;

• - C) the adjacent lesions in the liver, lung and mediastinum can be considered as a metastatic lesion if one isocentric irradiation can be used;

• For simultaneous oligostasis, the feasibility of primary focus radiotherapy should be evaluated, and the primary focus must be capable of receiving radiotherapy before being enrolled;For the primary lesion, SBRT or fractionated radiotherapy can be applied according to the site and surrounding invasion.

• For the heterogeneous oligometastasis of the primary lesion that has received surgery or local radiotherapy, the feasibility of local radiotherapy should be evaluated when the local recurrence lesion occurs, and the local recurrence lesion can be treated with subdivided radiotherapy or SBRT before inclusion;

• Patients with intracranial metastasis are allowed to be enrolled, but the intracranial lesions should be treated in advance and be in a stable state, and the number of intracranial lesions should be counted within the number of metastases.

• Patients should be enrolled within 35 days after the last systemic treatment;

• 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 is 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.

• The investigator does not consider the participant to be eligible for this study.

• Metastatic lesions involving esophagus, stomach, small intestine or mesenteric lymph nodes;

• The metastatic lesion is adjacent to the primary radiation range, and the radiotherapy physician cannot tolerate the secondary radiotherapy;

• Malignant pleural effusion without obvious remission after first-line chemotherapy.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Lung Adenocarcinoma

Intervention

Drug:
• Bevacizumab Injection
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 until disease progression or intolerable toxicity occurs.

Radiation:
• chest radiation
The patients receive SBRT radiotherapy for the primary (if any) and metastatic lesions or divided radiotherapy with or without concurrent chemotherapy.

Drug:
• concurrent chemotherapy
weekly docetaxel(25mg/?) and nedaplatin(25mg/?) concurrent with chest radiation

Locations

Country	Name	City	State
China	Sun yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (19)

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* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS	Progression-free survival in patients	3-year
Secondary	OS	overall survival in patients	3-year
Secondary	response rate		3-year
Secondary	rate of grade 3-4 radiation esophagitis		3-year
Secondary	rate of grade 3-4 radiation pneumonitis		3-year