Endostar for Locally Recurrent Nasopharyngeal Carcinoma

A Phase II Randomized Controlled Study to Compare Endostar and IMRT vs. IMRT Alone for Locally Recurrent Nasopharyngeal Carcinoma Patients

The purpose of this study is to determine whether endostar and IMRT is effective in the treatment of locally recurrent nasopharyngeal carcinoma patients compared with IMRT alone.

Study Overview

• Status: Unknown
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Endostatins; Radiation: IMRT

Detailed Description

Locally recurrent nasopharyngeal carcinoma (NPC) may be salvaged by intensity modulated-radiotherapy (IMRT), but severe late toxicities become the most common reason of death in IMRT salvaged NPC patients.

The aim of this phase II randomized controlled study is to address the efficacy of concurrent Endostar (Endostatins) with IMRT to reduce the occurrence of severe late toxicities compared with IMRT alone for locally recurrent NPC patients.

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • First People's Hospital of Foshan
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center
    • Guangzhou, Guangdong, China, 510000
      • Cancer Center of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510000
      • The First Affiliated Hospital of Clinical Medicine of G.D.P.U.
  • Jiangxi
    • GanZhou, Jiangxi, China, 341000
      • The First Hospital of Gannan Medical University
    • Ganzhou, Jiangxi, China, 341000
      • The Affiliated Ganzhou Hospital of Nanchang University
    • NanChang, Jiangxi, China, 330006
      • Second Affiliated Hospital of Nanchang University
    • NanChang, Jiangxi, China, 330029
      • JiangXi Province Tumor 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:

1. Pathologically or clinically confirmed locally recurrent nasopharyngeal carcinoma;
2. No evidence of distant metastasis
3. More than 1 year from the end of the first course of radiotherapy
4. Male, or female not in the phase of lactating or pregnancy
5. ECOG 0-2
6. Aged 18-70 years old
7. WBC count ≥4×109/L, neutrophile granulocyte count≥1.5×109/L, PLT count ≥100×109/L, Hb ≥9g/L
8. Total bilirubin, AST, ALT≤2.0 times of upper normal limits; creatinine ≤1.5 times of upper normal limits
9. Written informed consort signed

Exclusion Criteria:

1. Only regionally recurrence
2. Evidence of distant metastasis
3. Prior invasive malignancy; noninvasive cancers (For example, carcinoma in situ of the bladder, oral cavity, or cervix are all permissible) are permitted
4. Severe, active co-morbidity
5. Prior anti-tumor treatment after diagnosis of local recurrence
6. MRI was not performed 3 months after the first course of radiotherapy
7. Abnormal function of heart, brain and lungs, etc
8. Lactation or pregnancy
9. Severe nasopharyngeal mucosal necrosis at the diagnosis of local recurrence

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: IMRT and concurrent Endostar; IMRT and concurrent Endostar (Endostatins) to treat locally recurrent NPC patients; Endostar is to give from the first day of IMRT, 201mg, civ d1-14, q3w for two cycles. IMRT is to give GTV 60Gy in 27 fractions.	Drug: Endostatins; Endostar (Endostatins) is to give from the first day of IMRT, 201mg, civ d1-14, q3w for two cycles.; Other Names: Endostar; Radiation: IMRT; IMRT is to give GTV 60Gy in 27 fractions.
EXPERIMENTAL: IMRT alone; IMRT alone to treat locally recurrent NPC patients. IMRT is to give GTV 60Gy in 27 fractions.	Radiation: IMRT; IMRT is to give GTV 60Gy in 27 fractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with grade 4-5 late adverse events as assessed by RTOG/EORTC Late Radiation Morbidity Scoring Schema	From 3 months after the end of IMRT to 1 year after the end of IMRT

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with severe acute toxicities as assessed by CTCAE v3.0	From the beginning of IMRT to 3 months after the end of IMRT
Overall survival	From the beginning the IMRT to 3 year after the end of IMRT

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: First People's Hospital of Foshan; Affiliated Cancer Hospital & Institute of Guangzhou Medical University; Second Affiliated Hospital of Nanchang University; The Affiliated Ganzhou Hospital of Nanchang University; JiangXi Province Tumor Hospital; The First Affiliated Hospital of Clinical Medicine of G.D.P.U.; The First Hospital of Gannan Medical University
• Investigators: Principal Investigator: Fei Han, M.D., Ph.D., China: Ethics Committee

Publications and helpful links

General Publications

• Han F, Zhao C, Huang SM, Lu LX, Huang Y, Deng XW, Mai WY, Teh BS, Butler EB, Lu TX. Long-term outcomes and prognostic factors of re-irradiation for locally recurrent nasopharyngeal carcinoma using intensity-modulated radiotherapy. Clin Oncol (R Coll Radiol). 2012 Oct;24(8):569-76. doi: 10.1016/j.clon.2011.11.010. Epub 2011 Dec 29.
• Zhang K, Yang S, Zhu Y, Mo A, Zhang D, Liu L. Protection against acute radiation-induced lung injury: a novel role for the anti-angiogenic agent Endostar. Mol Med Rep. 2012 Aug;6(2):309-15. doi: 10.3892/mmr.2012.903. Epub 2012 May 4.
• Peng F, Xu Z, Wang J, Chen Y, Li Q, Zuo Y, Chen J, Hu X, Zhou Q, Wang Y, Ma H, Bao Y, Chen M. Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models. PLoS One. 2012;7(4):e34646. doi: 10.1371/journal.pone.0034646. Epub 2012 Apr 9.
• Tong RT, Boucher Y, Kozin SV, Winkler F, Hicklin DJ, Jain RK. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res. 2004 Jun 1;64(11):3731-6. doi: 10.1158/0008-5472.CAN-04-0074.
• Tian YM, Guan Y, Xiao WW, Zeng L, Liu S, Lu TX, Zhao C, Han F. Long-term survival and late complications in intensity-modulated radiotherapy of locally recurrent T1 to T2 nasopharyngeal carcinoma. Head Neck. 2016 Feb;38(2):225-31. doi: 10.1002/hed.23880. Epub 2015 May 27.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2015
• Primary Completion (ACTUAL): March 1, 2020
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: February 27, 2015
• First Submitted That Met QC Criteria: December 16, 2015
• First Posted (ESTIMATE): December 21, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 3, 2021
• Last Update Submitted That Met QC Criteria: January 31, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: IMRT; NPC; recurrent; Endostar
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Endostatins
• Other Study ID Numbers: NPC201501