Clinical trial NCT01335009: Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma
Official title: A Study of the Efficacy and PK/PD Relationship of Monotherapy MORAb-004 in Subjects With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Melanoma
Keywords: melanoma
malignant
metastatic
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2011-04-13
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a global, Phase 2, open label, dose selection, proof-of-concept study to assess progression free survival in subjects with metastatic melanoma.

Approximately 80 subjects at 29 sites in the U.S., U.K., Germany and Australia will be randomized into one of two dose groups: 2 mg/kg, 4 mg/kg. Weekly treatment will continue until disease progression.

Subjects must have measurable disease by CT Scan or MRI and must have completed at least one prior round of chemotherapy.

Subjects will be assessed for Efficacy, PK/PD, Overall survival, and Safety (Adverse Events/Adverse Events of Interest, Electrocardiograms (ECG's), clinical labs, physical exams/vital signs, tolerability).

Detailed description: MORAb-004 is a monoclonal antibody directed against endosialin, a cell surface glycoprotein, which is expressed on cells involved in tumor vasculature. Studies have found endosialin to play a key role in tumor growth and neovessel formation in numerous cancer types including melanoma. Preclinical pharmacological studies have shown that MORAb-004 is a potentially useful anti-cancer agent. This clinical trial is being performed to determine the efficacy of MORAb-004 at two dose levels in subjects with metastatic melanoma, as well as to establish serum pharmacokinetics and pharmacodynamics of the antibody.

Eligibility criteria: Inclusion Criteria:

* Be surgically sterile or consent to use a medically acceptable method of contraception throughout the study period.
* Histologically confirmed diagnosis of metastatic melanoma
* At least 1 prior systemic treatment for metastatic melanoma with disease progression following treatment
* Measurable disease, as defined by RECIST v1.1, assessed within 4 weeks prior to study entry
* At least 3 week interval between first infusion of test article and most recent prior systemic anticancer therapy. All treatment-associated toxicity must be resolved to less than or equal to Grade 1 before the administration of MORAb-004
* Have a life expectancy of at least 3 months as estimated by the investigator
* Have other significant medical conditions well-controlled and stable, in the opinion of the investigator, for at least 30 days prior to Study Day 1
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
* Have sites of disease amenable to the protocol-specified biopsy (Note: All participants will have protocol-specified biopsy at Screening. The second, on-treatment biopsy will be mandatory in the first 30 randomized participants only. For all other participants, the second biopsy is optional.
* Laboratory tests results prior to Study Day 1 within limits as outlined in protocol

Exclusion Criteria:

* Have received no prior systemic treatment for metastatic melanoma
* Evidence of other active malignancy requiring treatment within the last 5 years (other than basal cell or squamous cell carcinoma of the skin), or active brain metastasis
* Clinically significant heart disease (Congestive heart failure of New York Heart Association \[NYHA\] Class 3 or 4, angina not well controlled by medication, or myocardial infarction within 6 mos.), or ECGs demonstrating clinically significant arrhythmias
* Have any other serious systemic disease, including active bacterial or fungal infection, or any medical condition requiring cytotoxic therapy or chronic (at least 4 consecutive weeks) systemic corticosteroid use
* Have active viral hepatitis or symptomatic Human immunodeficiency virus (HIV) infection
* Be breast-feeding, pregnant, or likely to become pregnant during the study
* Known allergic reaction to a prior monoclonal antibody therapy
* Previous treatment with MORAb-004
* Brain metastasis

Primary outcomes:
measure: Percentage of Participants With Progression-free Survival (PFS) at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With PFS at Weeks 16 and 52
timeFrame: Week 16 and Week 52
measure: Overall Survival (OS)
timeFrame: Date of first study treatment (Day 1) to date of death or up to approximately 2 years 7 months
measure: Percentage of Participants With Overall Response
timeFrame: Date of first study treatment (Day 1) to complete response or partial response, assessed up to approximately 2 years 7 months
measure: Optimal Biologic Dosing (OBD) of Morab-004
timeFrame: Day 1 Cycle 1 (Cycle length = 28 days)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Pinnacle Oncology
state: Arizona
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center, Anschutz Cancer Pavilion
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Chicago
country: United States
facility: The University Of Chicago
state: Illinois
city: Park Ridge
country: United States
facility: Oncology Specialists, SC
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospital
state: Iowa
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Morristown
country: United States
facility: Atlantic Health
state: New Jersey
city: New York
country: United States
facility: New York University Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Bethlehem
country: United States
facility: St. Luke's Hospital & Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah Huntsman Cancer Institute
state: Utah
city: Camperdown
country: Australia
facility: Sydney Cancer Center - Royal Prince Alfred Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Newcastle Melanoma Unit, Calvery Mater Newcastle
state: New South Wales
city: Westmead
country: Australia
facility: The Crown Princess Mary Cancer Centre, Westmead Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Essen
country: Germany
facility: Universitatsklinikum Essen, Klinik fur Dermatologie
city: Mainz
country: Germany
facility: Universitats-Hautklinik
city: Tuebingen
country: Germany
facility: Eberhard Karls University Tuebingen
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
Study officials:
References: