ELLIPSE Study A Phase 1 study evaluating the tolerance of bevacizumab nasal spray in the treatment of epistaxis in hereditary hemorrhagic telangiectasia

被引:36
作者
Dupuis-Girod, S. [1 ,2 ]
Ambrun, A. [3 ]
Decullier, E. [4 ,5 ,6 ]
Samson, G. [4 ,5 ,6 ]
Roux, A. [4 ,5 ,6 ]
Fargeton, A-E [1 ,2 ]
Rioufol, C. [7 ,8 ]
Schwiertz, V. [7 ]
Disant, F. [3 ]
Chapuis, F. [4 ,5 ,6 ]
Donazzolo, Y. [9 ]
Paintaud, G. [10 ]
Edery, P. [1 ,2 ]
Faure, F. [3 ]
机构
[1] Grp Hosp Est, Hosp Civils Lyon, Serv Genet, Bron, France
[2] Ctr Reference Malad Rendu Osler, Bron, France
[3] Hop Edouard Herriot, Hosp Civils Lyon, Serv ORL, Lyon, France
[4] Hosp Civils Lyon, Pole IMER, Unite Rech Clin, Lyon, France
[5] Univ Lyon, EAM Sante Individu Soc 4128, Lyon, France
[6] Univ Lyon 1, F-69365 Lyon, France
[7] Ctr Hosp Lyon Sud, Hosp Civils Lyon, Unite Pharm Clin Oncol, F-69310 Pierre Benite, France
[8] UFR Lyon Sud, EMR CTO Ciblage Therapeut Oncol 3738, Pierre Benite, France
[9] Ctr Hosp Lyon Sud, Eurofins Optimed, F-69310 Pierre Benite, France
[10] CHRU Tours, Lab Pharmacol Toxicol, Tours, France
关键词
Hereditary hemorrhagic telangiectasia; rare diseases; epistaxis; Phase 1 clinical study; nasal spray; bevacizumab; SEPTUM PERFORATION; ENDOTHELIAL-CELLS; CANCER; MANAGEMENT; MUTATIONS; TRANSPORT; THERAPY; DISEASE; PATIENT; GENE;
D O I
10.4161/mabs.28025
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: Hereditary hemorrhagic telangiectasia (HHT) is a dominantly inherited genetic vascular disorder in which epistaxis is the most frequent manifestation, responsible for high morbidity. Management of this symptom has no standard, and local treatments are often aggressive. Their efficacy is variable and has not been proven. Anti-angiogenic drugs, such as bevacizumab, are a new treatment strategy. Its systemic administration in patients with HHT improves liver damage-related symptoms and epistaxis. To limit the systemic adverse effects of bevacizumab and to ease administration, a local administration seems suitable. Primary objective: To evaluate the tolerance of increasing doses of bevacizumab administered as a nasal spray in patients with HHT-related epistaxis. Secondary objectives were to study the bioavailability and efficacy of bevacizumab against epistaxis when given as a nasal spray. Methodology: Phase 1, randomized, double-blind, placebo-controlled, monocentric study performed sequentially (dose escalation) on 5 groups of 8 patients. Each group was made up of 6 verum and 2 placebos. Five increasing doses of bevacizumab nasal spray (25 mg/mL) were evaluated: 12.5, 25, 50, 75 and 100 mg. Results: A total of 40 patients were included between October 2011 and October 2012. Bevacizumab nasal spray was well tolerated in all patients and the drug was not detected in their serum. No dose limiting toxicity was observed. No efficacy was observed at any dose in this study. Conclusion: Based on these results, bevacizumab nasal spray is a safe treatment of epistaxis in HHT. However, a randomized Phase 2 study is needed to determine its efficacy. Trial Registration: ClinicalTrials.gov Identifier #NCT01507480
引用
收藏
页码:793 / 798
页数:6
相关论文
共 43 条
  • [41] S-1 and oxaliplatin (SOX) plus bevacizumab versus mFOLFOX6 plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer: updated overall survival analyses of the open-label, noninferiority, randomised phase III: SOFT study
    Baba, Hideo
    Yamada, Yasuhide
    Takahari, Daisuke
    Matsumoto, Hiroshi
    Yoshida, Kazuhiro
    Nakamura, Masato
    Yoshida, Motoki
    Iwamoto, Shigeyoshi
    Shimada, Ken
    Komatsu, Yoshito
    Sasaki, Yasutsuna
    Satoh, Taroh
    Takahashi, Keiichi
    Mishima, Hideyuki
    Muro, Kei
    Watanabe, Masahiko
    Sakata, Yuh
    Morita, Satoshi
    Shimada, Yasuhiro
    Sugihara, Kenichi
    ESMO OPEN, 2017, 2 (01)
  • [42] A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (Glassia®) in the Treatment of Recent-Onset Type 1 Diabetes
    Lebenthal, Yael
    Brener, Avivit
    Hershkovitz, Eli
    Shehadeh, Naim
    Shalitin, Shlomit
    Lewis, Eli C.
    Elias, Dana
    Haim, Alon
    Barash, Galia
    Loewenthal, Neta
    Zuckerman-Levin, Nehama
    Stein, Michal
    Tov, Naveh
    Rachmiel, Marianna
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2019, 20 (23)
  • [43] Capecitabine in combination with oxaliplatin and bevacizumab (AXELOX) as 1st line treatment for fit and vulnerable elderly patients (aged >70 years) with metastatic colorectal cancer (mCRC): a multicenter phase II study of the Hellenic Oncology Research Group (HORG)
    Lambros Vamvakas
    Alexios Matikas
    Athanasios Karampeazis
    Dora Hatzidaki
    Stelios Kakolyris
    Charalampos Christophylakis
    Ioannis Boukovinas
    Aris Polyzos
    Vassilis Georgoulias
    John Souglakos
    BMC Cancer, 14