Recombinant Human Endostatin Continued Pumping Into Vein Combining With CCRT in Unresectable Stage III NSCLC

Phase 1

Completed

• Conditions: Stage III Non-small-Cell Lung Cancer
• Interventions: Drug: Recombinant human endostatin; Drug: Etoposide (50mg/m2) IV (in the vein) on day 1 to day 5 of a 28-day cycle for 2 cycles; Drug: cisplatinum (50mg/m2) IV (in the vein) on day 1 and day 8 of a 28-day cycle for 2 cycles; Other: laboratory biomarker analysis; Other: CT perfusion imaging

• Registration Number: NCT01733589
• Lead Sponsor: Zhejiang Cancer Hospital

Brief Summary

Resistance of hypoxic tumor cells to radiation is a significant reason of failure in the local control of tumors, especially the squamous cell carcinomas. Preclinical models have shown that Endostar may transiently "normalize" the tumor vasculature to make it more efficient for oxygen delivery, thereby providing a window of opportunity for enhanced sensitivity to radiation treatment. This study is to evaluate the safety, toxicity, and efficacy of the addition of Endostar Continued Pumping into Vein to the standard CCRT regimen in patients with unresectable stage III NSCLC.

Detailed Description

Primary

Evaluate the efficacy and safety of Endostar combined with concurrent chemo-radiotherapy (CCRT) in patients with unresectable stage III non-small-cell lung cancer (NSCLC).

Secondary

Measure changes in VEGF and other angiogenic cytokines and antiangiogenic factors in plasma samples from these patients.

Evaluate the application of CT perfusion imaging to determine changes in tumor vascular mophology and function during treatment.

Study Timeline

• Study Start: 2012-11
• Study First Submitted: 2012-11-02
• Study First Submitted QC: 2012-11-20
• Study First Posted: 2012-11-27
• Primary Completion: 2015-06
• Study Completion: 2015-06
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-11
• Last Update Posted: 2017-07-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 73

Inclusion Criteria

• untreated histologic or cytologic of NSCLC verified
• inoperable stage IIIA or IIIB NSCLC
• measurable disease by RECIST
• 18~70 years of age
• an ECOG PS of 0 to 1
• absolute neutrophil count (ANC) of ≥1500/μL, hemoglobin ≥10gm/dL, platelet ≥100,000/μL
• serum creatinine ≤1.25 times of upper limit of normal (ULN), calculated creatinine clearance (CrCl) of ≥60ml/min
• bilirubin 1.5×ULN, AST and ALT less than 2.5×ULN, alkaline phosphatase less than 5×ULN
• forced vital capacity in 1 second (FEV1) higher than 0.8 L
• CB6 is normal
• Written informed consent

Exclusion Criteria

• a history of other malignant diseases
• any contraindications for chemoradiotherapy
• distant metastasis
• malignant pleural and/or pericardial effusion
• pregnant or nursing
• preexisting bleeding diatheses or coagulopathy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Recombinant Human Endostatin	cisplatinum (50mg/m2) IV (in the vein) on day 1 and day 8 of a 28-day cycle for 2 cycles	All patients received recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7. During week 2 through 8, patients received etoposide 50mg/m2 days 1-5 and cisplatin 50mg/m2 on day 1,8, every 4 weeks for two cycles with concurrent thoracic radiation at 60\~66Gy in 30\~33 fractions for 6\~7 weeks.
Recombinant Human Endostatin	laboratory biomarker analysis	All patients received recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7. During week 2 through 8, patients received etoposide 50mg/m2 days 1-5 and cisplatin 50mg/m2 on day 1,8, every 4 weeks for two cycles with concurrent thoracic radiation at 60\~66Gy in 30\~33 fractions for 6\~7 weeks.
Recombinant Human Endostatin	CT perfusion imaging	All patients received recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7. During week 2 through 8, patients received etoposide 50mg/m2 days 1-5 and cisplatin 50mg/m2 on day 1,8, every 4 weeks for two cycles with concurrent thoracic radiation at 60\~66Gy in 30\~33 fractions for 6\~7 weeks.
Recombinant Human Endostatin	Etoposide (50mg/m2) IV (in the vein) on day 1 to day 5 of a 28-day cycle for 2 cycles	All patients received recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7. During week 2 through 8, patients received etoposide 50mg/m2 days 1-5 and cisplatin 50mg/m2 on day 1,8, every 4 weeks for two cycles with concurrent thoracic radiation at 60\~66Gy in 30\~33 fractions for 6\~7 weeks.
Recombinant Human Endostatin	Recombinant human endostatin	All patients received recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7. During week 2 through 8, patients received etoposide 50mg/m2 days 1-5 and cisplatin 50mg/m2 on day 1,8, every 4 weeks for two cycles with concurrent thoracic radiation at 60\~66Gy in 30\~33 fractions for 6\~7 weeks.

Primary Outcome Measures

Name	Time	Method
progression-free survival	2-year	from beginning treatment to progressive disease or the last follow-up

Secondary Outcome Measures

Name	Time	Method
Response rate	1 month	complete response(CR); partial response(PR); stable disease(SD); progressive disease(PD)
overall survival	5 years	from date of beginning treatment until date of death
treatment related toxicities	3 months	radiation-induced esophagitis; radiation-induced pneumonia

Trial Locations

Locations (1)

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China