NCT02442466

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.

Trial Health

10
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for early_phase_1

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2011

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2012

Completed
3 years until next milestone

First Submitted

Initial submission to the registry

April 26, 2015

Completed
17 days until next milestone

First Posted

Study publicly available on registry

May 13, 2015

Completed
Last Updated

May 20, 2015

Status Verified

May 1, 2015

Enrollment Period

1 year

First QC Date

April 26, 2015

Last Update Submit

May 18, 2015

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

  • Tumour response by size measurement and histological examination

    3 to14 days

Secondary Outcomes (4)

  • Measuring changes in tumor cell proliferation by histological analyses using Ab staining

    3 to 14 days

  • Evaluation of changes in mRNA as well as protein expression levels of Endothelin Receptor B by PCR and Ab staining

    3 to 14 days

  • Evaluation of changes in blood vessels formation by histological examination using Ab staining

    3 to 14 days

  • Evaluation of changes in immune cell infiltration by histological examination using Ab staining

    3 to 14 days

Study Arms (2)

Endothelin receptor B inhibitor BQ-788

EXPERIMENTAL

Intra-lesion administration of an Endothelin Receptor B inhibitor (BQ-788)

Drug: Endothelin Receptor B inhibitor BQ788

PBS

EXPERIMENTAL

Intra-lesion administration of vehicle

Drug: PBS

Interventions

Endothelin Receptor B inhibitor BQ788DRUG
Endothelin receptor B inhibitor BQ-788
PBSDRUG
PBS

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (6)

  • 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.

    PMID: 8632985BACKGROUND

  • 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.

    PMID: 9826680BACKGROUND

  • 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.

    PMID: 10500205BACKGROUND

  • 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.

    PMID: 15604257BACKGROUND

  • 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.

    PMID: 15906230BACKGROUND

  • 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.

    PMID: 26330458DERIVED

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Study Design

Study Type
interventional
Phase
early phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 26, 2015

First Posted

May 13, 2015

Study Start

May 1, 2011

Primary Completion

May 1, 2012

Last Updated

May 20, 2015

Record last verified: 2015-05