A Phase II Clinical Trial of Chemotherapy With or Without Endostar® Continuous Intravenous Infusion in Refractory NPC

NCT02590133 | Unknown Phase 2 DMC

• 1 other identifier: B2015-031-01
• Study Type: interventional
• Target: 328
• Locations: 1 country
• Sites: 1

Brief Summary

We define refractory nasopharyngeal carcinoma as the following: recurrence with radiation brain injury after radiotherapy, recurrence after the second or more courses of radiotherapy, standard treatment failure after recurrence, and first-line treatment failure after multiple distant metastasis. There is no standard treatment for refractory nasopharyngeal carcinoma. Platinum plus 5-Fu is the classic regimen for primary treatment of nasopharyngeal carcinoma. Endostatin is a multiple targeted angiogenesis inhibitor acting on tumor associated neovascular endothelial cells, normalizing the morphology and function of tumor vasculature, and indirectly leading to the quiescence or reduction of tumors. The purpose of this phase II clinical trial is to determine the efficacy and safety of nedaplatin plus continuous low dose 5-Fu intravenous infusion combined with endostar® (Recombinant Human Endostatin Injection) continuous intravenous infusion compared with nedaplatin plus continuous low dose 5-Fu intravenous infusion alone in refractory nasopharyngeal carcinoma. The study hypothesis is that nedaplatin plus continuous low dose 5-Fu intravenous infusion combined with endostar® continuous intravenous infusion is effective and safe in refractory nasopharyngeal carcinoma.

Conditions

Nasopharyngeal Carcinoma

Keywords

Refractory Nasopharyngeal Carcinoma, Endostar, 5-Fu

Outcome Measures

Primary Outcomes (1)

• objective response (OR) rate based on Recist 1.1 edition

  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 Outcomes (5)

• Disease Control Rate (DCR)

  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

• Progress Free Survival (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

• Overall Survival (OS)

  From the date of first drug administration until the date of death, assessed up to 36 months

• Number of participants with adverse events (AEs) and serious adverse events (SAEs)

  From the date of first drug administration, evaluation was performed every cycle during the treatment and then every 3 months after the completion of the treatment up to 36 months, using NCI CTCAE version 4.0

• Quality of life

  From the date of first drug administration, evaluation was performed every cycle during the treatment and then every 3 months after the completion of the treatment up to 36 months, using EORTC quality of life questionnaire (QLQ)-C30

Study Arms (2)

Nedaplatin+5-Fu+Endostar

EXPERIMENTAL

Drug: Recombinant Human Endostatin Injection (Endostar) Endostar, 15mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total Drug: Fluorouracil (5-Fu) 5-Fu, 200mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total Drug: Nedaplatin Nedaplatin, 80mg/m2/d, intravenous drip on d1 and d28 each cycle, 60 days as one cycle, 6 cycles in total

Drug: Recombinant Human Endostatin Injection (Endostar); Drug: Fluorouracil (5-Fu); Drug: Nedaplatin

Nedaplatin+5-Fu

ACTIVE COMPARATOR

Drug: Fluorouracil (5-Fu) 5-Fu, 200mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total Drug: Nedaplatin Nedaplatin, 80mg/m2/d, intravenous drip on d1 and d28 each cycle, 60 days as one cycle, 6 cycles in total

Drug: Fluorouracil (5-Fu); Drug: Nedaplatin

Interventions

Recombinant Human Endostatin Injection (Endostar) DRUG

15mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total

Also known as: Endostar

Nedaplatin+5-Fu+Endostar

Fluorouracil (5-Fu) DRUG

200mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total

Also known as: 5-Fu

Nedaplatin+5-Fu; Nedaplatin+5-Fu+Endostar

Nedaplatin DRUG

80mg/m2/d, intravenous drip on d1 and d28 each cycle, 60 days as one cycle, 6 cycles in total

Also known as: Nedaplait

Nedaplatin+5-Fu; Nedaplatin+5-Fu+Endostar

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients have provided a signed Informed Consent Form.
• Histologically confirmed diagnosis of refractory nasopharyngeal carcinoma (the best), or when histology is difficult to obtained, the following clinical diagnosis of refractory nasopharyngeal carcinoma must be confirmed: clear and directional clinical symptoms, at least two kinds of imaging diagnosis on the basis of magnetic resonance (MR), and clear and directional signs.
• Age: 18-70 years old.
• Without dysfunction of heart, lung, liver, kidney, and hematopoiesis, and normal electrocardiogram.
• Karnofsky Performance Scores ≥ 50, Life expectancy ≥ 3 months, tolerance to at least two cycles of chemotherapy.
• At least one measurable tumor based on RECIST 1.1 ( longest diameter: ≥20 mm by CT or magnetic resonance (MR) scan)
• No history of serious allergic to biologic agents
• No history of other malignant tumors, except cured cervical carcinoma in situ and basal skin cancer.

You may not qualify if:

• Having the serious cardiovascular disease or other serious complications.
• Woman in pregnancy and breast-feeding.
• Allergic to intervention drugs and dextran.
• Patients participated in clinical trials of other drugs within 4 weeks.
• Use of other chemotherapy drugs, biological treatment, and Chinese medicine anti-cancer drugs at the same time.

Sponsors & Collaborators

• Yun-fei Xia: lead

Study Sites (1)

Department of Radiation Oncology, Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (15)

• Zhang F, Wu K, Gao F, Zhang W, Shi F, Li C. Refractory nasopharyngeal carcinoma: positron emission tomography combined with computed tomography-guided 125I seed implantation therapy after repeated traditional radiochemotherapy. Otolaryngol Head Neck Surg. 2013 Sep;149(3):417-23. doi: 10.1177/0194599813491221. Epub 2013 May 28.

  PMID: 23715683 BACKGROUND

• Gao Y, Huang HQ, Bai B, Cai QC, Wang XX, Cai QQ. Treatment outcome of docetaxel, capecitabine and cisplatin regimen for patients with refractory and relapsed nasopharyngeal carcinoma who failed previous platinum-based chemotherapy. Expert Opin Pharmacother. 2014 Feb;15(2):163-71. doi: 10.1517/14656566.2014.866652. Epub 2013 Dec 3.

  PMID: 24295173 BACKGROUND

• Peng PJ, Ou XQ, Chen ZB, Liao H, Peng YL, Wang SY, Zhang HY, Lin Z. Multicenter phase II study of capecitabine combined with nedaplatin for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy. Cancer Chemother Pharmacol. 2013 Aug;72(2):323-8. doi: 10.1007/s00280-013-2203-0. Epub 2013 Jun 1.

  PMID: 23728706 BACKGROUND

• Fandi A, Taamma A, Azli N, Bachouchi M, Yanes B, Armand JP, Cvitkovic E. Palliative treatment with low-dose continuous infusion 5-fluorouracil in recurrent and/or metastatic undifferentiated nasopharyngeal carcinoma type. Head Neck. 1997 Jan;19(1):41-7. doi: 10.1002/(sici)1097-0347(199701)19:13.0.co;2-v.

  PMID: 9030944 BACKGROUND

• Chen C, Wang FH, Wang ZQ, An X, Luo HY, Zhang L, Chen YC, Xu RH, Li YH. Salvage gemcitabine-vinorelbine chemotherapy in patients with metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Oral Oncol. 2012 Nov;48(11):1146-51. doi: 10.1016/j.oraloncology.2012.05.021. Epub 2012 Jun 27.

  PMID: 22748450 BACKGROUND

• Zheng J, Wang G, Yang GY, Wang D, Luo X, Chen C, Zhang Z, Li Q, Xu W, Li Z, Wang D. Induction chemotherapy with nedaplatin with 5-FU followed by intensity-modulated radiotherapy concurrent with chemotherapy for locoregionally advanced nasopharyngeal carcinoma. Jpn J Clin Oncol. 2010 May;40(5):425-31. doi: 10.1093/jjco/hyp183. Epub 2010 Jan 19.

  PMID: 20085903 BACKGROUND

• Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov. 2007 Apr;6(4):273-86. doi: 10.1038/nrd2115.

  PMID: 17396134 BACKGROUND

• Folkman J. Antiangiogenesis in cancer therapy--endostatin and its mechanisms of action. Exp Cell Res. 2006 Mar 10;312(5):594-607. doi: 10.1016/j.yexcr.2005.11.015. Epub 2005 Dec 22.

  PMID: 16376330 BACKGROUND

• 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.

  PMID: 22496834 BACKGROUND

• Kisker O, Becker CM, Prox D, Fannon M, D'Amato R, Flynn E, Fogler WE, Sim BK, Allred EN, Pirie-Shepherd SR, Folkman J. Continuous administration of endostatin by intraperitoneally implanted osmotic pump improves the efficacy and potency of therapy in a mouse xenograft tumor model. Cancer Res. 2001 Oct 15;61(20):7669-74.

  PMID: 11606410 BACKGROUND

• 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. doi: 10.1093/annonc/mdi318. Epub 2005 Jul 12.

  PMID: 16012180 BACKGROUND

• Rong B, Yang S, Li W, Zhang W, Ming Z. Systematic review and meta-analysis of Endostar (rh-endostatin) combined with chemotherapy versus chemotherapy alone for treating advanced non-small cell lung cancer. World J Surg Oncol. 2012 Aug 24;10:170. doi: 10.1186/1477-7819-10-170.

  PMID: 22917490 BACKGROUND

• Ke QH, Zhou SQ, Huang M, Lei Y, Du W, Yang JY. Early efficacy of Endostar combined with chemoradiotherapy for advanced cervical cancers. Asian Pac J Cancer Prev. 2012;13(3):923-6. doi: 10.7314/apjcp.2012.13.3.923.

  PMID: 22631672 BACKGROUND

• Xu R, Ma N, Wang F, Ma L, Chen R, Chen R, Kebinu M, Ma L, Han Z, Ayixiamu, Mayier M, Su P, Naman Y, Jieensi H, Yang H, Adili A, Aili S, Liu J. Results of a randomized and controlled clinical trial evaluating the efficacy and safety of combination therapy with Endostar and S-1 combined with oxaliplatin in advanced gastric cancer. Onco Targets Ther. 2013 Jul 25;6:925-9. doi: 10.2147/OTT.S46487. Print 2013.

  PMID: 23926435 BACKGROUND

• 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.

  PMID: 25198661 BACKGROUND

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Endostatins; endostar protein; Fluorouracil; nedaplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Angiostatic Proteins; Angiogenic Proteins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Collagen Type XVIII; Non-Fibrillar Collagens; Collagen; Extracellular Matrix Proteins; Scleroproteins; Biological Factors; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Yun-fei Xia, Prof

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yun-fei Xia, Prof

CONTACT

+86-13602805461; xiayf@sysucc.org.cn

Chen Chen, MD

CONTACT

+86-13570487011; chenchen@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center

Study Record Dates

• First Submitted: October 27, 2015
• First Posted: October 28, 2015
• Study Start: July 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2020
• Last Updated: December 22, 2017

Record last verified: 2017-10

Locations

CN (1)