A Clinical Study of Recombinant Human Vascular Endothelial Inhibitor in Combination With PRaG for Advanced Refractory Non-small Cell Lung Cancer

Phase 2

Recruiting

• Conditions: Advanced Solid Tumor; Refractory Tumor
• Interventions: Radiation: Radiotherapy; Drug: PD-1/PD-L1 inhibitor; Drug: Granulocyte-macrophage colony-stimulating factor subcutaneous injection; Drug: Interleukin 2 subcutaneous injection; Drug: Endostatin

• Registration Number: NCT06047860
• Lead Sponsor: Second Affiliated Hospital of Soochow University

Brief Summary

Exploring the efficacy and safety of recombinant human vascular endothelial inhibitor (Endo) in combination with Bragg therapy in advanced refractory non-small cell lung

Detailed Description

Radiotherapy:

Start radiotherapy on the first day of treatment, as described in 6.2 above;

GM-CSF treatment:

GM-CSF 200 μg on the first day of treatment, administered subcutaneously daily for 7 days; IL-2 treatment. 2 million IU of IL-2 on the day after GM-CSF, administered subcutaneously daily for 7 days;

Immunotherapy:

PD-1/PD-L1 inhibitors within one week of radiotherapy;

Recombinant human vascular endothelial inhibitor (Endo):

Recombinant human vascular endothelial inhibitor (Endo) 210 mg CIV72h starting on the first day of treatment, every 21 days for a minimum of ≥ 2 cycles of this combination therapy.

Maintenance treatment phase:

Maintenance with PD-1/PD-L1 inhibitor in combination with recombinant human vascular endothelial inhibitor (Endo) until progression or intolerable side effects.

Study Timeline

• Study Start: 2023-06-16
• Status Verified: 2023-09
• Study First Submitted: 2023-09-14
• Study First Submitted QC: 2023-09-14
• Last Update Submitted: 2023-09-14
• Study First Posted: 2023-09-21
• Last Update Posted: 2023-09-21
• Primary Completion: 2024-12-30
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Patients aged 18-75 years;
2. Patients enrolled must be eligible for patients with recurrent or metastatic advanced non-small cell lung cancer, with a clear pathological diagnosis report or history of disease, with guidelines that do not clearly recommend standard treatment regimens or who are unable to tolerate standard treatment regimens, and with clear measurable metastatic lesions (>1cm);
3. No congestive heart failure, unstable angina, or unstable arrhythmia within the last 6 months.
4. Patient activity status score of 0-3 on the Eastern Cooperative Oncology Group (ECOG) scale with life expectancy assessed at ≥3 months.
5. No previous severe haematopoietic, cardiac, pulmonary, hepatic or renal abnormalities and immunodeficiency.
6. Absolute T-lymphocyte values ≥ 0.5 times the lower limit of normal and neutrophils ≥ 1.0 x 109/L; AST and ALT ≤ 3.0 times the upper limit of normal (≤ 5.0 times the upper limit of normal for hepatocellular carcinoma/metastatic liver cancer); creatinine ≤ 3.0 times the upper limit of normal, 1 week prior to enrollment.
7. Patients must have the ability to understand and voluntarily sign the informed consent form.

Exclusion Criteria

1. Pregnant or breastfeeding women;
2. Persons with a history of other malignant disease in the last 5 years, except cured skin cancer and carcinoma in situ of the cervix;
3. Persons with a history of uncontrolled epilepsy, central nervous system disorders or psychiatric disorders whose clinical severity, as judged by the investigator, may prevent the signing of an informed consent or affect the patient's compliance with drug therapy;
4. Clinically significant (i.e., active) cardiac disease such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmias requiring pharmacological intervention, or a history of myocardial infarction within the last 12 months;
5. Persons requiring immunosuppressive therapy for organ transplantation;
6. Known major active infection or, in the judgement of the investigator, major haematological, renal, metabolic, gastrointestinal, endocrine dysfunction or metabolic disorders, or other serious uncontrolled concomitant disease;
7. Hypersensitivity to any investigational drug component;
8. Persons with a history of immunodeficiency, including those who have tested positive for HIV or have other acquired or congenital immunodeficiency diseases, or a history of organ transplantation, or other immune-related diseases requiring long-term oral hormone therapy
9. Persons with active tuberculosis infection;
10. Those with interstitial lung disease or non-infectious pneumonia that may prevent the assessment of pulmonary toxicity associated with the study or the manager;
11. Other conditions that, in the opinion of the investigator, are not suitable for enrolment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention group	PD-1/PD-L1 inhibitor	M-CSF 200 μg administered subcutaneously daily for 7 days on the first day of treatment; IL-2 2 million IU administered subcutaneously daily for 7 days the day after GM-CSF; PD-1/PD-L1 inhibitor within one week of radiotherapy; Recombinant human vascular endothelial inhibitor (Endo) 210 mg CIV72h starting on the first day of treatment, every 21 days for a minimum of ≥ 2 cycles of this combination therapy. Maintenance treatment phase: Maintenance with PD-1/PD-L1 inhibitor in combination with recombinant human vascular endothelial inhibitor (Endo) until progression or intolerable side effects.
Intervention group	Interleukin 2 subcutaneous injection	M-CSF 200 μg administered subcutaneously daily for 7 days on the first day of treatment; IL-2 2 million IU administered subcutaneously daily for 7 days the day after GM-CSF; PD-1/PD-L1 inhibitor within one week of radiotherapy; Recombinant human vascular endothelial inhibitor (Endo) 210 mg CIV72h starting on the first day of treatment, every 21 days for a minimum of ≥ 2 cycles of this combination therapy. Maintenance treatment phase: Maintenance with PD-1/PD-L1 inhibitor in combination with recombinant human vascular endothelial inhibitor (Endo) until progression or intolerable side effects.
Intervention group	Radiotherapy	M-CSF 200 μg administered subcutaneously daily for 7 days on the first day of treatment; IL-2 2 million IU administered subcutaneously daily for 7 days the day after GM-CSF; PD-1/PD-L1 inhibitor within one week of radiotherapy; Recombinant human vascular endothelial inhibitor (Endo) 210 mg CIV72h starting on the first day of treatment, every 21 days for a minimum of ≥ 2 cycles of this combination therapy. Maintenance treatment phase: Maintenance with PD-1/PD-L1 inhibitor in combination with recombinant human vascular endothelial inhibitor (Endo) until progression or intolerable side effects.
Intervention group	Granulocyte-macrophage colony-stimulating factor subcutaneous injection	M-CSF 200 μg administered subcutaneously daily for 7 days on the first day of treatment; IL-2 2 million IU administered subcutaneously daily for 7 days the day after GM-CSF; PD-1/PD-L1 inhibitor within one week of radiotherapy; Recombinant human vascular endothelial inhibitor (Endo) 210 mg CIV72h starting on the first day of treatment, every 21 days for a minimum of ≥ 2 cycles of this combination therapy. Maintenance treatment phase: Maintenance with PD-1/PD-L1 inhibitor in combination with recombinant human vascular endothelial inhibitor (Endo) until progression or intolerable side effects.
Intervention group	Endostatin	M-CSF 200 μg administered subcutaneously daily for 7 days on the first day of treatment; IL-2 2 million IU administered subcutaneously daily for 7 days the day after GM-CSF; PD-1/PD-L1 inhibitor within one week of radiotherapy; Recombinant human vascular endothelial inhibitor (Endo) 210 mg CIV72h starting on the first day of treatment, every 21 days for a minimum of ≥ 2 cycles of this combination therapy. Maintenance treatment phase: Maintenance with PD-1/PD-L1 inhibitor in combination with recombinant human vascular endothelial inhibitor (Endo) until progression or intolerable side effects.

Primary Outcome Measures

Name	Time	Method
overall response rate(ORR)	six weeks	ORR is defined as the proportion of patients who have a partial (PR) or complete response (CR) to therapy among the total number of evaluable patients.
Progression free survival (PFS)	six weeks	The time from commencement of treatment to disease progression or death from any cause.
Overall survival (OS)	six weeks	The time from the first day of enrollment to death from any cause.
Disease control rate (DCR)	six weeks	the percentage of patients who have achieved complete response (CR), partial response (PR) and stable disease (SD)
Incidence of adverse events	six weeks	the rate of AE

Trial Locations

Locations (1)

The Second Affiliated Hospital of SchoowUniversity; 🇨🇳 Suzhou, China