Clinical trial NCT04973293: Preoperative Sintilimab Combined With Bevacizumab and Chemotherapy for Resectable Non-Small Cell Lung Cancer
Official title: The Safety and Feasibility of Preoperative Sintilimab Combined With Bevacizumab and Chemotherapy for Locally Advanced Resectable Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Lung Neoplasm Malignant
Keywords: Non-small cell lung cancer
Neoadjuvant therapy
Immunotherapy
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2021-07-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Neoadjuvant chemotherapy followed by surgery has been recommended as the standard treatment for locally advanced and resectable non-small cell lung cancer (NSCLC). However, its efficacy remains to be improved. Drugs targeting PD-1/PD-L1 pathway have been proven to be effective for late-stage NSCLC, and anti-angiogenesis agents targeting VEGF (bevacizumab) has also been used for the first line treatment of advanced or metastatic NSCLC. Therefore, we conduct this single-arm clinical trial, which aims to investigate the safety and feasibility of neoadjuvant sintilimab combined with bevacizumab and chemotherapy followed by surgery in treating locally advanced and resectable NSCLC.

Detailed description: Lung cancer is one of the most common malignancies around the world. Neoadjuvant chemotherapy followed by surgery has been recommended as the standard treatment for locally advanced and resectable non-small cell lung cancer (NSCLC). However, its efficacy remains to be improved. Bevacizumab targeting VEGF is a widely used antitumor drugs in different types of malignancies, including late-stage NSCLC. Immune checkpoint inhibitor (ICI) targeting PD-1 has also been confirmed to be effective in NSCLC patients. Therefore, we conduct this prospective single-arm clinical trial, to investigate the safety and feasibility of neoadjuvant sintilimab (ICI targeting PD-1) combined with bevacizumab and chemotherapy followed by surgery in treating locally advanced and resectable NSCLC. Twenty patients with stage II-IIIA NSCLC will be enrolled. And the primary endpoint of this study is the safety of this newly developed neoadjuvant treatment. The secondary endpoints are feasibility, radiological response and rate of major pathological response.

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed, previously untreated and surgically resectable non-small cell lung cancer (stage II-IIIA, patients with squamous cell carcinoma or EGFR mutation should not be included);
2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
3. Satisfactory preoperative laboratory testing and adequate pulmonary function for surgery;
4. Patients approve and sign the informed consent.

Exclusion Criteria:

1. Pancoast tumor, squamous cell carcinoma, large-cell carcinoma and sarcomatoid carcinoma;
2. Patients with active autoimmune disease or history of autoimmune disease;
3. Patients who have a condition requiring systemic treatment with either prednisone or other immunosuppressive medications;
4. Patients with a history of symptomatic interstitial lung disease;
5. History of allergy to study drug components;
6. Women must not be pregnant or breast-feeding;
7. Men with female partners that are not willing to use contraception;
8. Patients who have received prior chemotherapy, anti-angiogenesis therapy and immunotherapy for this malignancy or for any other past malignancy;
9. Patients who have received prior treatment for non-small cell lung cancer;
10. Any mental or psychological condition which would not permit the patient to complete the study or understand the patient information;
11. Patients who have major hemoptysis within the past 4 weeks, tumor has invasion or is close to great vessels;
12. Patients with high risk of major bleeding;
13. Patients who have arterial thrombotic events, esophageal varices, peptic ulcers, wounds or bone fractures;
14. Patients who have prior malignancies;
15. HIV, HBV, HCV infection or active pulmonary tuberculosis;
16. Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.

Primary outcomes:
measure: Safety (Rate of grade 3 and higher grade treatment-related adverse events)
timeFrame: From date of treatment allocation until surgery or up to at least 90 days after last dose of preoperative treatment
Secondary outcomes:
measure: Feasibility (Completion rate of neoadjuvant treatment and surgery)
timeFrame: From date of treatment allocation until surgery, assessed up to 5 months
measure: Major Pathological Response Rate
timeFrame: Two weeks after surgery
measure: Radiographic Response
timeFrame: From date of treatment allocation and during treatment period up to 4 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Hecheng Li, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: