Multicenter Phase I/II Clinical Trial of Recombinant Human Endostatin Continued Pumping Into Vein Combining With Concurrent Chemo-Radiotherapy in the Patients With Unresectable Stage III Non-small-Cell Lung Cancer
Overview
- Phase
- Phase 1
- Intervention
- Recombinant human endostatin
- Conditions
- Stage III Non-small-Cell Lung Cancer
- Sponsor
- Zhejiang Cancer Hospital
- Enrollment
- 73
- Locations
- 1
- Primary Endpoint
- progression-free survival
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
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.
Intervention: 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.
Intervention: Etoposide (50mg/m2) IV (in the vein) on day 1 to day 5 of a 28-day cycle for 2 cycles
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.
Intervention: cisplatinum (50mg/m2) IV (in the vein) on day 1 and day 8 of a 28-day cycle for 2 cycles
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.
Intervention: laboratory biomarker analysis
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.
Intervention: CT perfusion imaging
Outcomes
Primary Outcomes
progression-free survival
Time Frame: 2-year
from beginning treatment to progressive disease or the last follow-up
Secondary Outcomes
- Response rate(1 month)
- overall survival(5 years)
- treatment related toxicities(3 months)