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

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

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.

Study Overview

• Status: Unknown
• Conditions: Non Small Cell Lung Cancer; Bevacizumab; Brain Metastases; Sintilimab
• Intervention / Treatment: Drug: sintilimab

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen University of Cancer Center
      • Contact: Likun Chen, doctor; Phone Number: 13798019964; Email: chenlk@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sintilimab and Bevacizumab; Sintilimab 200mg d1 and Bevacizumab 15mg/kg d1 every 21 days	Drug: sintilimab; Sintilimab 200mg d1 and Bevacizumab 15mg/kg d1 q21d; Other Names: bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
iORR	intracranial objective response rate	3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
iPFS	intracranial progression free survival	3.5 yesrs
ORR	objective response rate	3.5 years
PFS	progression free survival	3.5 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Director: Likun Chen, doctor, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2019
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: December 25, 2019
• First Submitted That Met QC Criteria: December 25, 2019
• First Posted (Actual): December 30, 2019

Study Record Updates

• Last Update Posted (Actual): December 30, 2019
• Last Update Submitted That Met QC Criteria: December 25, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Brain Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: B2019-050-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No