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

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

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.

Study Overview

• Status: Completed
• Conditions: Stage III Non-small-Cell Lung Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; 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: CT perfusion imaging

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 Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: 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.

Other: laboratory biomarker analysis; Drug: Recombinant human endostatin; Recombinant human endostatin(7.5mg/m2/24h) Continued Pumping Into Vein through 5 days at week 1, 3, 5, and 7,combined with concurrent chemo-radiotherapy.; 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: CT perfusion imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival	from beginning treatment to progressive disease or the last follow-up	2-year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Collaborators: Fudan University; Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Fujian Cancer Hospital; Peking University Cancer Hospital & Institute; Tianjin Medical University Cancer Institute and Hospital; Shandong Cancer Hospital and Institute; Jiangsu Cancer Institute & Hospital; The First People's Hospital of Lianyungang
• Investigators: Principal Investigator: Ming Chen, M.D., Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2012
• Primary Completion (ACTUAL): June 1, 2015
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: November 2, 2012
• First Submitted That Met QC Criteria: November 20, 2012
• First Posted (ESTIMATE): November 27, 2012

Study Record Updates

• Last Update Posted (ACTUAL): July 14, 2017
• Last Update Submitted That Met QC Criteria: July 11, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: chemoradiotherapy; Recombinant human endostatin; Non-small-Cell Lung Cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Etoposide; Cisplatin; Endostatins
• Other Study ID Numbers: [2012]-10-24