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

Metastatic Melanoma Clinical Trial

Official title:

A Study of the Efficacy and PK/PD Relationship of Monotherapy MORAb-004 in Subjects With Metastatic Melanoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01335009
• Other study ID #: MORAb-004-201MEL
• Secondary ID: 2011-001282-40
• Status: Completed
• Phase: Phase 2
• Start date: May 16, 2011
• Est. completion date: April 10, 2020

Study information

• Verified date: April 2021
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: April 10, 2020
• Est. primary completion date: December 2, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
Australia	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
Germany	Universitatsklinikum Essen, Klinik fur Dermatologie	Essen
Germany	Universitats-Hautklinik	Mainz
Germany	Eberhard Karls University Tuebingen	Tuebingen
United Kingdom	The Royal Marsden Hospital	London
United Kingdom	Weston Park Hospital	Sheffield
United States	University of Colorado Cancer Center, Anschutz Cancer Pavilion	Aurora	Colorado
United States	St. Luke's Hospital & Health Network	Bethlehem	Pennsylvania
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	The University Of Chicago	Chicago	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Iowa Hospital	Iowa City	Iowa
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 Minnesota	Minneapolis	Minnesota
United States	Atlantic Health	Morristown	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	New York University Cancer Institute	New York	New York
United States	Oncology Specialists, SC	Park Ridge	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Utah Huntsman Cancer Institute	Salt Lake City	Utah
United States	Pinnacle Oncology	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Countries where clinical trial is conducted

United States,  Australia,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Progression-free Survival (PFS) at Week 24	PFS was defined as the time (in weeks) from the date of randomization to the date of the first sign of disease progression (PD) based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or date of death, regardless of cause. PD greater than or equal to (>=) 20 percent (%) increase in the nadir of total tumor burden (TTB) (minimum 5 millimeter [mm]). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received a new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was started. PFS was analyzed using Kaplan Meier method.	Week 24
Secondary	Percentage of Participants With PFS at Weeks 16 and 52	PFS was defined as the time (in weeks) from the date of randomization to the date of the first observation of PD (RECIST version 1.1) or date of death, regardless of the cause. PD >=20% increase in the nadir of TTB (minimum 5 mm). Participants who were alive with no disease progression had their PFS time censored at the date of their last tumor assessment. Participants who received new anti-cancer therapy before disease progression had their PFS time censored at the date of their last tumor assessment before the new anti-cancer therapy was initiated. PFS was based on the Kaplan-Meier method.	Week 16 and Week 52
Secondary	Overall Survival (OS)	OS was defined as the time (in weeks) from the date of randomization to the date of death, regardless of cause. In the absence of death confirmation, or for participants alive at the time of analysis, the survival time was censored at the date of the last study follow-up. OS was calculated using the Kaplan-Meier method. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).	Date of first study treatment (Day 1) to date of death or up to approximately 2 years 7 months
Secondary	Percentage of Participants With Overall Response	ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) that occurred (defined by RECIST version 1.1) using CT/MRI. Per RECIST 1.1, CR= disappearance of all lesions; PR greater than or equal to (>=) 30percent (%) decrease from baseline in TTB. As per planned analysis, efficacy outcomes was planned to be analyzed until cut-off date (02 December 2013).	Date of first study treatment (Day 1) to complete response or partial response, assessed up to approximately 2 years 7 months
Secondary	Optimal Biologic Dosing (OBD) of Morab-004	OBD is defined as the dose level/exposure level at which three parameters are met: 1) adequate pharmacokinetic (PK) profile with a serum half-life (t1/2) of >=48 hours, 2) at least minimal demonstration of antitumor efficacy (50% or greater PFS rate at 16 weeks), and 3) change of 25% or greater from baseline value in any of the pharmacodynamic (PD) parameters assessed in the study in 30% of participants at that dose level.	Day 1 Cycle 1 (Cycle length = 28 days)