Clinical trial NCT03989830: Second-Line Chemotherapy Combined With Endostatin for Recurrent/Metastatic HN Epithelial Tumors
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Head and Neck Neoplasms
Keywords: Endostatins
Head and Neck Neoplasms
Lead sponsor: Peking University
Sponsor class: OTHER
Collaborators: name: Peking University
name: Peking University Cancer Hospital & Institute
First posted: 2019-06-18
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: 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:
measure: Objective Response Rate (ORR)
timeFrame: 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
measure: Progress Free Survival (PFS)
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: From the date of first drug administration until the date of death, assessed up to 36 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Sun Yan, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.
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. doi: 10.3892/ol.2012.856. Epub 2012 Aug 8.
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.
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.
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.
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.
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. doi: 10.1093/annonc/mdi318. Epub 2005 Jul 12.
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.