Sintilimab Combined With Bevacizumab for Brain Metastases From Non-small Cell Lung Cancer

Non Small Cell Lung Cancer Clinical Trial

Official title:

Prospective Phase II Clinical Study of Sintilimab Combined With Bevacizumab for Driving Gene-negative, Asymptomatic Brain Metastases From Non-small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04213170
• Other study ID #: B2019-050-01
• Status: Recruiting
• Phase: Phase 2
• Start date: April 29, 2019
• Est. completion date: December 2022

Study information

• Verified date: May 2019
• Source: Sun Yat-sen University
• Contact: Likun Chen, doctor
• Phone: 13798019964
• Email: chenlk[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective phase II clinical study to assess the efficacy of Sintilimab combined with Bevacizumab for driving gene-negative, asymptomatic brain metastases from non-small cell lung cancer by intracranial ORR(iORR),also iPFS,ORR and PFS.The safety and tolerability is evaluated as well.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients with NSCLC confirmed by histology or cytology;

2. Patients with asymptomatic brain metastasis or brain metastasis whose symptoms of intracranial hypertension have been alleviated after dehydration treatment should keep the clinical stable state for at least 2 weeks.For patients requiring hormone dehydration therapy, hormone therapy should be discontinued 3 days before the first dose of the study drug.

3. Appraisable disease, the diameter of at least one measurable lesion in the brain must be 5mm;

4. The detection results of tumor tissue biomarkers should meet the following conditions simultaneously: EGFR has no sensitive mutation;ALK rearrangement negative;for never treated patients, they also needed to meet PD-L1 >50% or TMB>12Mut/Mb (second-generation sequencing).

5. Adult patients (= 18 years and =75 years). ECOG Performance Status 0 or 1 Life expectancy of at least 12 weeks.,Haemoglobin ³ 10.0 g/dl, Absolute neutrophil count (ANC) ³1.5 x 109/L, platelets ³ 100 x 109/L. Total bilirubin £ 1.5 x upper limit of normal (ULN). ALT and AST < 2.5 x ULN in the absence of liver metastases, or < 5 x ULN in case of liver metastases. Creatinine clearance ³ 60ml/min (calculated according to Cockcroft-gault formula).

6. Ability to follow study and follow-up procedures;

7. Prior to the implementation of any trial-related procedures, a written informed consent shall be signed.

Exclusion Criteria:

1. Mixed non-small cell and small cell carcinoma;

2. Brain metastasis with hemorrhage;

3. Currently participating in interventional clinical research and treatment, or receiving other research drugs or using research instruments within 4 weeks before the first dose;

4. Previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs targeting another stimulation or synergistic inhibition of T cell receptors (e.g., CTLA-4, CD137);

5. Received solid organ or blood system transplantation;

6. Received >30GY pulmonary radiotherapy 6 months before the first dose;

7. Active autoimmune diseases requiring systemic treatment (such as the use of disease-relieving drugs, corticosteroids or immunosuppressants) occurred within 2 years before the first dose.Alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic;

8. Received systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of the study or diagnosed as immunodeficiency;a physiological dose of glucocorticoid (10 mg/ day of prednisone or equivalent) is permitted;

9. History of non-infectious pneumonia requiring glucocorticoid therapy or current interstitial pulmonary disease was found within 1 year before the first dose;

10. History of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive)

11. Untreated active hepatitis;

12. History of hemoptysis within 3 months prior to selection, that is, at least 1/2 teaspoon of blood was coughed up;

13. Imaging showed signs of tumor invasion into the great vessels.The investigator or radiologist must rule out patients whose tumors have completely approached, wrapped, or invaded the intravascular space of the great vessels

14. Serious uncontrolled coagulation disorder or thrombi-embolic complications within 6 months prior to study start or history of serious bleeding complications.

15. Major surgical procedures within 4 weeks prior to study entry.

16. Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion.

17. Non-healing wound, active peptic ulcer or bone fracture.

18. History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of enrollment

Related Conditions & MeSH terms

• Bevacizumab
• Brain Metastases
• Brain Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Neoplasm Metastasis
• Non Small Cell Lung Cancer
• Sintilimab

Intervention

Drug:
• sintilimab
Sintilimab 200mg d1 and Bevacizumab 15mg/kg d1 q21d

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	iORR	intracranial objective response rate	3.5 years
Secondary	iPFS	intracranial progression free survival	3.5 yesrs
Secondary	ORR	objective response rate	3.5 years
Secondary	PFS	progression free survival	3.5 years