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

Primary Purpose

Metastatic Melanoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MORAb-004 (monoclonal antibody)
Sponsored by
Eisai Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Melanoma focused on measuring melanoma, malignant, metastatic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Pinnacle Oncology
  • The Angeles Clinic and Research Institute
  • University of California Los Angeles
  • University of Colorado Cancer Center, Anschutz Cancer Pavilion
  • Yale University
  • The University Of Chicago
  • Oncology Specialists, SC
  • University of Iowa Hospital
  • University of Minnesota
  • Washington University School of Medicine
  • Atlantic Health
  • New York University Cancer Institute
  • Memorial Sloan-Kettering Cancer Center
  • University of North Carolina at Chapel Hill
  • Duke University Medical Center
  • St. Luke's Hospital & Health Network
  • Thomas Jefferson University
  • Fox Chase Cancer Center
  • University of Pittsburgh Cancer Institute
  • University of Utah Huntsman Cancer Institute
  • Sydney Cancer Center - Royal Prince Alfred Hospital
  • Newcastle Melanoma Unit, Calvery Mater Newcastle
  • The Crown Princess Mary Cancer Centre, Westmead Hospital
  • Princess Alexandra Hospital
  • Universitatsklinikum Essen, Klinik fur Dermatologie
  • Universitats-Hautklinik
  • Eberhard Karls University Tuebingen
  • The Royal Marsden Hospital
  • Weston Park Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

MORAb-004, 2 mg/kg

MORAb-004, 4 mg/kg

Arm Description

Biologic (monoclonal antibody)

Biologic (monoclonal antibody)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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).
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.

Full Information

First Posted
March 14, 2011
Last Updated
August 6, 2021
Sponsor
Eisai Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01335009
Brief Title
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

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
May 16, 2011 (Actual)
Primary Completion Date
December 2, 2013 (Actual)
Study Completion Date
April 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Melanoma
Keywords
melanoma, malignant, metastatic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MORAb-004, 2 mg/kg
Arm Type
Experimental
Arm Description
Biologic (monoclonal antibody)
Arm Title
MORAb-004, 4 mg/kg
Arm Type
Experimental
Arm Description
Biologic (monoclonal antibody)
Intervention Type
Biological
Intervention Name(s)
MORAb-004 (monoclonal antibody)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Progression-free Survival (PFS) at Week 24
Description
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.
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Percentage of Participants With PFS at Weeks 16 and 52
Description
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.
Time Frame
Week 16 and Week 52
Title
Overall Survival (OS)
Description
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).
Time Frame
Date of first study treatment (Day 1) to date of death or up to approximately 2 years 7 months
Title
Percentage of Participants With Overall Response
Description
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).
Time Frame
Date of first study treatment (Day 1) to complete response or partial response, assessed up to approximately 2 years 7 months
Title
Optimal Biologic Dosing (OBD) of Morab-004
Description
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.
Time Frame
Day 1 Cycle 1 (Cycle length = 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Pinnacle Oncology
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
19454
Country
United States
Facility Name
The Angeles Clinic and Research Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Facility Name
University of California Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Colorado Cancer Center, Anschutz Cancer Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
The University Of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Oncology Specialists, SC
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
Facility Name
University of Iowa Hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
19454
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Atlantic Health
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962
Country
United States
Facility Name
New York University Cancer Institute
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
19454
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
St. Luke's Hospital & Health Network
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18051
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
University of Pittsburgh Cancer Institute
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
University of Utah Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Sydney Cancer Center - Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Newcastle Melanoma Unit, Calvery Mater Newcastle
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
The Crown Princess Mary Cancer Centre, Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Facility Name
Universitatsklinikum Essen, Klinik fur Dermatologie
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Universitats-Hautklinik
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Eberhard Karls University Tuebingen
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Facility Name
The Royal Marsden Hospital
City
London
ZIP/Postal Code
SW3 6JJ
Country
United Kingdom
Facility Name
Weston Park Hospital
City
Sheffield
ZIP/Postal Code
S10 2SJ
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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