Efficacy Study of Pharmacokinetic(PK)/Pharmacodynamic(PD) Relationship of Monotherapy MORAb-004 in Metastatic Melanoma

NCT ID: NCT01335009

Last Updated: 2021-09-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-05-16
• Study Completion Date: 2020-04-10

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.

Conditions

Metastatic Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MORAb-004, 2 mg/kg

Biologic (monoclonal antibody)

Group Type: EXPERIMENTAL

MORAb-004 (monoclonal antibody)

Intervention Type: BIOLOGICAL

Subjects will receive one cycle of treatment with MORAb-004, administered intravenously, on Days 1, 8, 15, and 22 (4 administrations per cycle). Additional cycles will continue without interruption until disease progression occurs or clinical or symptomatic progression as suggested by an investigator.

MORAb-004, 4 mg/kg

Biologic (monoclonal antibody)

Group Type: EXPERIMENTAL

MORAb-004 (monoclonal antibody)

Intervention Type: BIOLOGICAL

Subjects will receive one cycle of treatment with MORAb-004, administered intravenously, on Days 1, 8, 15, and 22 (4 administrations per cycle). Additional cycles will continue without interruption until disease progression occurs or clinical or symptomatic progression as suggested by an investigator.

Interventions

MORAb-004 (monoclonal antibody)

Subjects will receive one cycle of treatment with MORAb-004, administered intravenously, on Days 1, 8, 15, and 22 (4 administrations per cycle). Additional cycles will continue without interruption until disease progression occurs or clinical or symptomatic progression as suggested by an investigator.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Pinnacle Oncology

Scottsdale, Arizona, United States

The Angeles Clinic and Research Institute

Los Angeles, California, United States

University of California Los Angeles

Los Angeles, California, United States

University of Colorado Cancer Center, Anschutz Cancer Pavilion

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

The University Of Chicago

Chicago, Illinois, United States

Oncology Specialists, SC

Park Ridge, Illinois, United States

University of Iowa Hospital

Iowa City, Iowa, United States

University of Minnesota

Minneapolis, Minnesota, United States

Washington University School of Medicine

St Louis, Missouri, United States

Atlantic Health

Morristown, New Jersey, United States

New York University Cancer Institute

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

St. Luke's Hospital & Health Network

Bethlehem, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, United States

Sydney Cancer Center - Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Newcastle Melanoma Unit, Calvery Mater Newcastle

Waratah, New South Wales, Australia

The Crown Princess Mary Cancer Centre, Westmead Hospital

Westmead, New South Wales, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Universitatsklinikum Essen, Klinik fur Dermatologie

Essen, , Germany

Universitats-Hautklinik

Mainz, , Germany

Eberhard Karls University Tuebingen

Tübingen, , Germany

The Royal Marsden Hospital

London, , United Kingdom

Weston Park Hospital

Sheffield, , United Kingdom

Countries

United States; Australia; Germany; United Kingdom

Other Identifiers

2011-001282-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MORAb-004-201MEL

Identifier Type: -

Identifier Source: org_study_id