Second-Line Chemotherapy Combined With Endostatin for Recurrent/Metastatic HN Epithelial Tumors

Head and Neck Neoplasms Clinical Trial

— SLICER  

Official title:

A Phase II Study of Second-line Chemotherapy Combined With Endostatin for Recurrent/Metastatic Head and Neck Epithelial Tumors That Cannot be Re-irradiated or Re-operated After Fist-line Platinum-based Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03989830
• Other study ID #: BJCH-2019YJZ24
• Status: Recruiting
• Phase: Phase 2
• Start date: July 29, 2019
• Est. completion date: June 30, 2022

Study information

• Verified date: October 2020
• Source: Peking University
• Contact: Sun Yan, MD
• Phone: 0086-10-88196217
• Email: lisaysun[@]139.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The prognoses of recurrent/metastatic head and neck epithelial tumors after first-line platinum-based chemotherapy is poor. The efficacy of second-line chemotherapy for those patients that cannot be re-irradiated or re-operated is limited according to NCCN guideline and other published data. This study was designed to evaluate the efficacy and safety of endostatin combined with second-line chemotherapy for patients of recurrent/metastatic head and neck epithelial tumors that cannot be re-irradiated or re-operated after fist-line platinum-based chemotherapy.

Description:

The prognoses of recurrent/metastatic head and neck epithelial tumors after first-line platinum-based chemotherapy is poor. The efficacy of second-line chemotherapy for those patients that cannot be re-irradiated or re-operated is limited according to NCCN guideline and other published data. New agent for second-line treatment of recurrent and/or metastatic head and neck tumors is urgently needed. Recombinant human endostatin is an anti-angiogenetic target drug, which has been demonstrated a good efficacy for NSCLC. Studies about recombinant human endostatin in head and neck cancer mainly focus on NPC. And phase I study of endostatin combined with chemotherapy and/or radiotherapy for NPC showed a promising results.

This study was designed to evaluate the efficacy and safety of endostatin combined with second-line chemotherapy for patients of recurrent/metastatic head and neck epithelial tumors that cannot be re-irradiated or re-operated after fist-line platinum-based chemotherapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 53
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age =18 years old,<70 years old.

2. KPS =70.

3. Histopathology confirmed head and neck epithelial tumors, ie. Squamous cell carcinoma, adenocarcinoma, mucoepidermoid carcinoma, et al.

4. Relapse or metastasize after fist-line platinum-based chemotherapy,and the lesions cannot be re-irradiated or re-operated.

5. At least one measurable lesion (RECIST 1.1 version).

6. Life expectancy = 6 months.

7. Adequate bone function: WBC=3.0x109/L, ANC=1.5 x109/L, HB=90g/L, PLT=100 x109/L. AST, ALT, Creatinine, urea nitrogen<1.25 ULN, normal coagulation function parameters.

Exclusion Criteria:

1. Malignant melanoma, lymphoma, other tumors from mesenchymal tissues.

2. Second primary malignant tumors.

3. Contraindications of chemotherapy: severe infections, significant cardiovascular disease, symptomatic arrythmia, uncontrolled diabetes mellitus, et al.

4. HIV infection, untreated chronic hepatitis B infection or carriers of HBV DNA copies >500IU/ml, active hepatitis C patients.

5. Uncontrolled hypertension.

6. Hemorrhagic tendency.

7. Epileptic seizure.

8. History of progression after anti-angiogenic target treatment.

9. History of allergy to recombinant human endostatin.

10. Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the last dose of study treatment. Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment.

11. Receiving treatment of other clinical trials.

Related Conditions & MeSH terms

• Head and Neck Neoplasms

Intervention

Drug:
• second-line chemotherapy
choose appropriate regimen according to efficacy and adverse effects of first-line chemotherapy. q3W regimen, 6 cycles.
• Recombinant human endostatin
7.5mg/m2/d,continuous intravenous pumping in 2ml/h for 5 days each cycle. Endostar(d-7) begins one week before chemotherapy(d0), first 5-day-pump(d-7 to d-2, 240ml, 2ml/h). Second 5-day-pump begins two days later (d1 to d5). the rest pumps can be done in the same manner. Three 5-day-pumps can be done during one chemotherapy cycle. Endostar will be pumped 18 weeks during 6 cycles'second-line chemotherapy.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing

Sponsors (3)

Lead Sponsor	Collaborator
Sun Yan	Beijing Cancer Hospital, Peking University

Country where clinical trial is conducted

China, 

References & Publications (9)

Cui C, Mao L, Chi Z, Si L, Sheng X, Kong Y, Li S, Lian B, Gu K, Tao M, Song X, Lin T, Ren X, Qin S, Guo J. A phase II, randomized, double-blind, placebo-controlled multicenter trial of Endostar in patients with metastatic melanoma. Mol Ther. 2013 Jul;21(7):1456-63. doi: 10.1038/mt.2013.79. Epub 2013 May 14. — View Citation

Guan Y, Li A, Xiao W, Liu S, Chen B, Lu T, Zhao C, Han F. The efficacy and safety of Endostar combined with chemoradiotherapy for patients with advanced, locally recurrent nasopharyngeal carcinoma. Oncotarget. 2015 Oct 20;6(32):33926-34. doi: 10.18632/oncotarget.5271. — View Citation

Hansma AH, Broxterman HJ, van der Horst I, Yuana Y, Boven E, Giaccone G, Pinedo HM, Hoekman K. Recombinant human endostatin administered as a 28-day continuous intravenous infusion, followed by daily subcutaneous injections: a phase I and pharmacokinetic study in patients with advanced cancer. Ann Oncol. 2005 Oct;16(10):1695-701. Epub 2005 Jul 12. — View Citation

Jin T, Li B, Chen XZ. A phase II trial of Endostar combined with gemcitabine and cisplatin chemotherapy in patients with metastatic nasopharyngeal carcinoma (NCT01612286). Oncol Res. 2013;21(6):317-23. doi: 10.3727/096504014X13983417587401. — View Citation

Li X, Gu G, Soliman F, Sanders AJ, Wang X, Liu C. The Evaluation of Durative Transfusion of Endostar Combined with Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer. Chemotherapy. 2018;63(4):214-219. doi: 10.1159/000493098. Epub 2018 Oct 22. — View Citation

Lu S, Li L, Luo Y, Zhang L, Wu G, Chen Z, Huang C, Guo S, Zhang Y, Song X, Yu Y, Zhou C, Li W, Liao M, Li B, Xu L, Chen P, Hu C, Hu C. A multicenter, open-label, randomized phase II controlled study of rh-endostatin (Endostar) in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer. J Thorac Oncol. 2015 Jan;10(1):206-11. doi: 10.1097/JTO.0000000000000343. — View Citation

Wen QL, Meng MB, Yang B, Tu LL, Jia L, Zhou L, Xu Y, Lu Y. Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice. Cancer Sci. 2009 Aug;100(8):1510-9. doi: 10.1111/j.1349-7006.2009.01193.x. Epub 2009 May 21. — View Citation

Ye W, Liu R, Pan C, Jiang W, Zhang L, Guan Z, Wu J, Ying X, Li L, Li S, Tan W, Zeng M, Kang T, Liu Q, Thomas GR, Huang M, Deng W, Huang W. Multicenter randomized phase 2 clinical trial of a recombinant human endostatin adenovirus in patients with advanced head and neck carcinoma. Mol Ther. 2014 Jun;22(6):1221-1229. doi: 10.1038/mt.2014.53. Epub 2014 Mar 25. — View Citation

Zhou J, Wang L, Xu X, Tu Y, Qin S, Yin Y. Antitumor activity of Endostar combined with radiation against human nasopharyngeal carcinoma in mouse xenograft models. Oncol Lett. 2012 Nov;4(5):976-980. Epub 2012 Aug 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Control Rate (DCR)	include complete remission, partial remission, and stable disease	From the date of first drug administration, evaluation of response was performed every cycle during the treatment and then every 3 months after the completion of the treatment up to 36 months
Secondary	Objective Response Rate (ORR)	include complete remission and partial remission	From the date of first drug administration, evaluation of response was performed every cycle during the treatment and then every 3 months after the completion of the treatment up to 36 months
Secondary	Progress Free Survival (PFS)	1,2 years PFS	From the date of first drug administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Secondary	Overall Survival (OS)	1,2 years OS	From the date of first drug administration until the date of death, assessed up to 36 months