Rh-Endostatin Combined With CCRT(50 Gy) Followed by Durvalumab Maintenance for the Treatment of Specific Phase III NSCLC

Study Overview
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Brief Summary
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A Study to Assess the Effects of Durvalumab following Rh-Endostatin combined with reduced-dose CCRT(50 Gy) in Patients with Stage III Unresectable Non-Small Cell Lung Cancer who can not tolerate 60 Gy irradiation.

Detailed Description
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A Phase II, Single-arm, Multi-centre Study of Durvalumab as Sequential Therapy in Patients with Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Rh-Endostatin combined with reduced-dose CCRT(50 Gy) Therapy (Relief)

Official Title
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Rh-Endostatin Combined With Low-dose CCRT(50 Gy) Followed by Durvalumab Maintenance for the Treatment of Specific Phase III NSCLC Who Can Not Tolerate 60 Gy Irradiation

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Recombinant human endostatin (Endostar)
* Radiation: Thoracic irradiation of 50 Gy with 3DCRT or IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age at 18-75 years. Documented evidence of NSCLC (locally advanced, unresectable, Stage III) Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) Eastern Cooperative Oncology Group performance status score (ECOG PS) of 0 to 1. Estimated life expectancy of more than 12 weeks. Exclusion Criteria: Prior exposure to any anti-PD-1 or anti-PD-L1 antibody. Active or prior autoimmune disease or history of immunodeficiency. Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV. Evidence of uncontrolled illness such as symptomatic congestive heart failure, uncontrolled hypertension or unstable angina pectoris. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Endostar combined Radiation<br> | Drug: Recombinant human endostatin (Endostar)<br>* Continuous intravenous infusion of endostar (Simcere Pharma- ceutical, Nanjing, China) was made over 120 h before the begin- ning of radiotherapy, and then repeated every two weeks. The dose was 7.5 mg/m2/24 h 120 h, 14 days/cycle. ECG monitoring was performed during the first delivery of endostar.<br>* Other names: Durvalumab;Radiation: Thoracic irradiation of 50 Gy with 3DCRT or IMRT<br>* Concurrent thoracic chemoradiotherapy with reduced irradiation dose of 50 Gy will be given to patients with unresectable stage III NSCLC who can not tolerate irradiation dose to 60 Gy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | PFS was defined as the time from randomization until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression). | up to approximately 3 years | 
| adverse events (AE) | Number of participants with adverse events as assessed by CTCAE v5.0 | 5 years from patient enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | OS was defined as the time from the date of randomization until death due to any cause. OS was calculated using the Kaplan-Meier technique. | up to 5 years from patient enrollment | 
| Objective Response Rate | ORR was defined as the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) per RECIST 1.1 for target lesions: CR: Disappearance of all target lesions; PR: >=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR. | Tumor scans performed at baseline then every  8 weeks up to 48 weeks, then every   12 weeks thereafter up to 3 three years |