Clinical trial NCT02442466: Proof of Concept Study With an Endothelin Receptor B Inhibitor (BQ-788) for Human Melanoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Melanoma
Lead sponsor: MelCure SA
Sponsor class: INDUSTRY
Collaborators: name: California Institute of Technology
name: University of Bern
name: Universitaire Ziekenhuizen KU Leuven
First posted: 2015-05-13
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: Intra-lesion administration of an Endothelin Receptor B inhibitor (BQ-788) or vehicle was preformed in 5 melanoma patients to have a preliminary analysis of safety, dose, duration and relevance of results observed in pre-clinical studies to the human disease.


Eligibility criteria: Inclusion Criteria:

* Written Informed consent
* Histologically confirmed melanoma
* Disease stage III or IV
* At least 2 injectable and surgically removable cutaneous metastasis
* Age \> 18 years
* Clinically stable medical condition

Exclusion Criteria:

* Primary ocular melanoma
* Symptomatic intracranial melanoma
* History of severe neurological, cardiovascular, renal, hepatic, endocrinological, respiratory, bone marrow, autoimmune or infectious (HIV) disease
* Pregnancy or lactation

Primary outcomes:
measure: Tumour response by size measurement and histological examination
timeFrame: 3 to14 days
Secondary outcomes:
measure: Measuring changes in tumor cell proliferation by histological analyses using Ab staining
timeFrame: 3 to 14 days
measure: Evaluation of changes in mRNA as well as protein expression levels of Endothelin Receptor B by PCR and Ab staining
timeFrame: 3 to 14 days
measure: Evaluation of changes in blood vessels formation by histological examination using Ab staining
timeFrame: 3 to 14 days
measure: Evaluation of changes in immune cell infiltration by histological examination using Ab staining
timeFrame: 3 to 14 days
Other outcomes:
Locations:
Study officials:
References:
citation: Lahav R, Ziller C, Dupin E, Le Douarin NM. Endothelin 3 promotes neural crest cell proliferation and mediates a vast increase in melanocyte number in culture. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3892-7. doi: 10.1073/pnas.93.9.3892.
citation: Lahav R, Dupin E, Lecoin L, Glavieux C, Champeval D, Ziller C, Le Douarin NM. Endothelin 3 selectively promotes survival and proliferation of neural crest-derived glial and melanocytic precursors in vitro. Proc Natl Acad Sci U S A. 1998 Nov 24;95(24):14214-9. doi: 10.1073/pnas.95.24.14214.
citation: Lahav R, Heffner G, Patterson PH. An endothelin receptor B antagonist inhibits growth and induces cell death in human melanoma cells in vitro and in vivo. Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11496-500. doi: 10.1073/pnas.96.20.11496.
citation: Lahav R, Suva ML, Rimoldi D, Patterson PH, Stamenkovic I. Endothelin receptor B inhibition triggers apoptosis and enhances angiogenesis in melanomas. Cancer Res. 2004 Dec 15;64(24):8945-53. doi: 10.1158/0008-5472.CAN-04-1510.
citation: Lahav R. Endothelin receptor B is required for the expansion of melanocyte precursors and malignant melanoma. Int J Dev Biol. 2005;49(2-3):173-80. doi: 10.1387/ijdb.041951rl.
citation: Wouters J, Hunger RE, Garrod T, Dubuis B, Hunziker T, van den Oord JJ, Lahav-le Coutre R. First-in-Human Proof-of-Concept Study: Intralesional Administration of BQ788, an Endothelin Receptor B Antagonist, to Melanoma Skin Metastases. Oncologist. 2015 Oct;20(10):1121-2. doi: 10.1634/theoncologist.2015-0139. Epub 2015 Sep 1.