- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02590133
A Phase II Clinical Trial of Chemotherapy With or Without Endostar® Continuous Intravenous Infusion in Refractory NPC
A Multi-institutional, Randomized Controlled, Phase II Clinical Trial on Comparison of Efficacy and Safety of Nedaplatin Plus 5-Fu Combined With and Without Endostar® Continuous Intravenous Infusion in Refractory Nasopharyngeal Carcinoma
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
With the extension of survival time in nasopharyngeal carcinoma(NPC), more and more patients suffer from 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. We define these four types as refractory nasopharyngeal carcinoma[1-2] due to the complex and high risk of treatment and poor prognosis. For recurrence and metastasis NPC, the objective response rate ranges from 25% to 46.4% with platinum-based, or 5-Fu-based, or gemcitabine-based salvage chemotherapy[2--5].
At present, there is no standard treatment for refractory nasopharyngeal carcinoma.
Most patients in this trial were pretreated with cisplatin-based chemotherapy. Nedaplatin has the equivalent antitumor effect with cisplatin and less renal toxicity and gastrointestinal toxicity in the treatment of NPC[6]. In addition, nedaplatin does not have the cross tolerance with cisplatin. After cisplatin failure, nedaplatin(80-100 mg/m2) still work in NPC treatment[3].
5-Fu is a classic, effective, and safe chemotherapeutic drug in NPC treatment. Low dose continuous intravenous infusion of 5-Fu(300mg/m2/d, 6 weeks) is a effective regimen for recurrent and metastasis NPC with low toxicity[4].
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[7-9]. Anti-angiogenic therapy might optimally require that endothelial cells be exposed to steady blood levels of the inhibitor, and blood levels of certain angiogenesis inhibitors (such as endostatin) that are too high or too low will be ineffective[7,10]. Endostar® is recombinant human endostatin injection with better medicinal properties, stability and curative effect. Hoekman K. etc conducted a phase I clinical pharmacokinetic study in advanced cancer and the results showed that continuous intravenous pump of endostar® is safe[11]. Moreover, endostar® combined with chemotherapy can improve the outcome of the chemotherapy alone and does not increase the treatment related toxicity, such as in advanced non-small-cell lung cancer[12], advanced cervical cancer[13], advanced gastric cancer[14] and also metastasis NPC[15].
Given that the patients in this trial have the following features: had received standard radical treatment, poor tolerance of treatment due to the toxicity after many courses of chemotherapy, and the present treatment goal is palliative therapy. Therefore, the treatment principle in this trial is using low toxicity, well tolerance treatment regimen to relieve and control tumor, improve the quality of life, and further to prolong the survival time.
Based on above background and considering the Efficacy and tolerability, we use nedaplatin plus continuous low dose 5-Fu intravenous infusion as chemotherapy regimen, and administrate endostar® in continuous intravenous infusion.
This phase II randomized controlled trial is to investigate 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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Yun-fei Xia, Prof
- Phone Number: +86-13602805461
- Email: xiayf@sysucc.org.cn
Study Contact Backup
- Name: Chen Chen, MD
- Phone Number: +86-13570487011
- Email: chenchen@sysucc.org.cn
Study Locations
-
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Guangdong
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Guangzhou, Guangdong, China, 510060
- Recruiting
- Department of Radiation Oncology, Sun Yat-Sen University Cancer Center
-
Contact:
- Yun-fei Xia, Prof.
- Phone Number: +86-13602805461
- Email: xiayf@sysucc.org.cn
-
Contact:
- Chen Chen, M.D.
- Phone Number: +86-13570487011
- Email: chenchen@sysucc.org.cn
-
Sub-Investigator:
- Chen Chen, M.D.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Nedaplatin+5-Fu+Endostar
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
|
15mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total
Other Names:
200mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total
Other Names:
80mg/m2/d, intravenous drip on d1 and d28 each cycle, 60 days as one cycle, 6 cycles in total
Other Names:
|
Active Comparator: Nedaplatin+5-Fu
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
|
200mg/m2/d, continuous intravenous infusion in 2ml/h for 30 days each cycle, 60 days as one cycle, 6 cycles in total
Other Names:
80mg/m2/d, intravenous drip on d1 and d28 each cycle, 60 days as one cycle, 6 cycles in total
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
objective response (OR) rate based on Recist 1.1 edition
Time Frame: 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
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease Control Rate (DCR)
Time Frame: 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
|
include complete remission, partial remission, and progressive 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
|
Progress Free Survival (PFS)
Time Frame: 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
|
3 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
|
Overall Survival (OS)
Time Frame: From the date of first drug administration until the date of death, assessed up to 36 months
|
3 years 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)
Time Frame: 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
|
Safety evaluation according to NCI Common Terminology Criteria (CTC) 4.0
|
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
Time Frame: 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
|
Quality of life evaluation according to EORTC quality of life questionnaire (QLQ)-C30
|
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
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Yun-fei Xia, Prof, Sun Yat-sen University
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Folkman J. Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov. 2007 Apr;6(4):273-86. doi: 10.1038/nrd2115.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
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
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Fluorouracil
- Endostar protein
- Endostatins
- Nedaplatin
Other Study ID Numbers
- B2015-031-01
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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