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Morphotek Investigation in Colorectal Cancer: Research of MORAb-004 (MICRO)

Phase 2
Terminated
Conditions
Colorectal Cancer
Metastatic Colorectal Cancer
Interventions
Drug: Placebo
Other: Best supportive care
Registration Number
NCT01507545
Lead Sponsor
Morphotek
Brief Summary

The purpose of this study is to evaluate whether therapy with MORAb-004 is effective and safe in the treatment of metastatic, colorectal cancer.

Detailed Description

Tumor endothelial marker-1 also referred to as TEM-1 is expressed in the supportive tissue, as well as, on the cells within the tumor. TEM-1, which is a cell surface glycoprotein, and is expressed in the stromal compartment (cells) of nearly all human tumors. In preclinical studies, it has been shown that TEM-1 plays a key role in tumor growth and the vascularization of tumors. There is evidence suggesting an association between the level of TEM-1, 7, 7R, 8 in relation to lymph node involvement and disease progression. MORAb-004 is a humanized immunoglobulin G (IgG1/κ) antibody directed against endosialin/TEM-1. Nonclinical pharmacological studies showed that MORAb-004 has the ability to block specific TEM-1 receptor-ligand interactions. Immunohistochemistry studies of human tumor biopsy samples demonstrate TEM-1 expression and MORAb-004 binding to tumor stromal cells, in particular mural cell compartment of neovessels and cancer-associated fibroblasts. All of which suggests a potential effective treatment. Researchers hypothesize that an antibody therapy that binds to TEM-1 may be efficacious in the treatment of metastatic, colorectal cancer. This clinical study is a proof of concept study to see if an anti-TEM-1 agent is safe and effective in the treatment of metastatic, colorectal cancer.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
154
Inclusion Criteria
  • Males and females >18 years old
  • Diagnosis of metastatic, colorectal cancer
  • Significant medical conditions must be well-controlled and stable for at least 30 days prior to the first treatment infusion
  • Be willing and able to provide written informed consent
Exclusion Criteria
  • No prior treatment for metastatic colorectal cancer
  • Other serious systemic diseases (bacterial or fungal)
  • Clinically significant heart disease or an arrhythmia on an ECG within the past 6 months
  • Known allergic reaction to monoclonal antibody therapy

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
PlaceboBest supportive care-
MORAb-004MORAb-004-
MORAb-004Best supportive care-
Primary Outcome Measures
NameTimeMethod
Progression-Free Survival (PFS)From the date of randomization to the date of the first observation of PD or death due to any cause (up to approximately 1 year 7 months)

PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 was defined as the time (in weeks) from the date of randomization to the date of the first observation of disease progression (PD) or death due to any cause. PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. If progression or death was not observed for a participant, the PFS time was censored at the date of last tumor assessment without evidence of progression prior to the date of initiation of further antitumor treatment. PFS was summarized for each treatment group using Kaplan-Meier estimation curves.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)From the date of randomization to the date of death due to any cause (up to approximately 1 year 7 months)

OS was defined as the time (in months) from the date of randomization to the date of death, regardless of the cause. OS was summarized for each treatment group using Kaplan-Meier estimation curves. In the absence of death confirmation or for participants alive at the time of analysis, the survival time was censored at the last date known to be alive.

Biomarkers Based OS, Within Treatment GroupFrom the date of randomization up to approximately 1 year 7 months

The statistical evidence to support the use of the biomarker identified in Stage 1 interim analysis for Stage 2 selection of participants as designed was not adequate to clearly define a biomarker responsive population. The study was terminated by the sponsor at the end of Stage 1 and enrollment of stage 2 did not occur due to futility, hence Stage 2 and biomarker based analysis for OS was not carried out.

Overall Response Rate (ORR)From the date of randomization to the first documentation of CR or PR (up to approximately 1 year 7 months)

ORR was defined as the percentage of subjects achieving either CR or PR using RECIST v.1.1. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Time to Tumor Response (TTR)From the date of randomization to first documentation of objective tumor response (CR or PR) (up to approximately 1 year 7 months)

Time to tumor response was defined for those participants with objective evidence of confirmed CR or PR as the time from randomization to first documentation of objective tumor response (CR or PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Duration of Response (DOR)From the date of first objective response (CR or PR) to objective tumor progression or death regardless of cause (up to approximately 1 year 7 months)

The DOR was defined as the time from first documentation of objective response (CR or PR) to the first documentation of objective tumor progression or death due to any cause. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Biomarkers Based PFS, Within Treatment GroupFrom the date of randomization up to approximately 1 year 7 months

The statistical evidence to support the use of the biomarker identified in Stage 1 interim analysis for Stage 2 selection of participants as designed was not adequate to clearly define a biomarker responsive population. The study was terminated by the sponsor at the end of Stage 1 and enrollment of stage 2 did not occur due to futility, hence Stage 2 and biomarker based analysis for PFS was not carried out.

Trial Locations

Locations (65)

Providence St. Joseph Medical Center-Disney Family Cancer Center

🇺🇸

Burbank, California, United States

St. Jude Heritage Healthcare

🇺🇸

Fullerton, California, United States

Comprehensive Blood and Cancer Center

🇺🇸

Bakersfield, California, United States

Siouxland Hematology-Oncology Associates, LLP

🇺🇸

Sioux City, Iowa, United States

Regions Hospital

🇺🇸

Saint Louis Park, Minnesota, United States

Mercy Cancer Center

🇺🇸

Toledo, Ohio, United States

The Thomas and Dorothy Leavey Cancer Center Northridge Hospital Medical Center

🇺🇸

Northridge, California, United States

Cancer Care Centers of Brevard

🇺🇸

Rockledge, Florida, United States

Suburban Hematology-Oncology Associates, P.C.

🇺🇸

Snellville, Georgia, United States

Central Baptist Hospital

🇺🇸

Lexington, Kentucky, United States

Christiana Care Health Services

🇺🇸

Newark, Delaware, United States

Lutheran Hematology & Oncology

🇺🇸

Wheat Ridge, Colorado, United States

Compass Research, LLC

🇺🇸

Orange City, Florida, United States

Ingalls Cancer Research Center

🇺🇸

Harvey, Illinois, United States

Grand Rapids Clinical Oncology Program

🇺🇸

Grand Rapids, Michigan, United States

St. Mary's Hospital / Green Bay Oncology

🇺🇸

Green Bay, Wisconsin, United States

Central Coast Medical Oncology

🇺🇸

Santa Maria, California, United States

Integrated Community Oncology Network / Cancer Specialists of North Florida

🇺🇸

Jacksonville, Florida, United States

Illinois CancerCare, P.C.

🇺🇸

Peoria, Illinois, United States

Suburban Hematology-Oncology Assoc., PC

🇺🇸

Lawrenceville, Georgia, United States

Medical and Surgical Specialists

🇺🇸

Galesburg, Illinois, United States

Essentia Health Duluth CCOP

🇺🇸

Duluth, Minnesota, United States

St. Mary's Hospital Regional Cancer Center

🇺🇸

Grand Junction, Colorado, United States

Hickman Cancer Center at Flower Hospital

🇺🇸

Sylvania, Ohio, United States

Mayo Clinic Florida Hematology/Oncology

🇺🇸

Jacksonville, Florida, United States

Pharma Resource

🇺🇸

East Providence, Rhode Island, United States

UCLA Hematology Oncology

🇺🇸

Santa Monica, California, United States

Oncology Specialists,S.C. Center for Advanced Care

🇺🇸

Park Ridge, Illinois, United States

Metro Minnesota CCOP

🇺🇸

Saint Louis Park, Minnesota, United States

Lahey Clinic

🇺🇸

Burlington, Massachusetts, United States

Coborn Cancer Center/ CentraCare Health Plaza

🇺🇸

Saint Cloud, Minnesota, United States

Medcenter One

🇺🇸

Bismarck, North Dakota, United States

John Hopkins University

🇺🇸

Baltimore, Maryland, United States

Weinberg Cancer Institute at Franklin Square

🇺🇸

Baltimore, Maryland, United States

Georgetown University

🇺🇸

Washington, District of Columbia, United States

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Colorado Cancer Research Program

🇺🇸

Denver, Colorado, United States

TriHealth Oncology Institute/Oncology Partners Network

🇺🇸

Cincinnati, Ohio, United States

Sharp Memorial Hospital

🇺🇸

San Diego, California, United States

CPMCRI / Pacific Hematology Oncology Associates

🇺🇸

San Francisco, California, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

CCCN

🇺🇸

Las Vegas, Nevada, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Central Hem/Onc Medical Group, Inc.

🇺🇸

Alhambra, California, United States

Medical Oncology & Hematology Associates (Clinic #1)

🇺🇸

Des Moines, Iowa, United States

Iowa Oncology Research Association

🇺🇸

Des Moines, Iowa, United States

Medical Oncology & Hematology Associates (Clinic #3)

🇺🇸

Clive, Iowa, United States

Hematology Oncology Associates of the Treasure Coast

🇺🇸

Port Saint Lucie, Florida, United States

Carle Cancer Center

🇺🇸

Urbana, Illinois, United States

Medical Oncology & Hematology Associates (Clinic #2)

🇺🇸

Des Moines, Iowa, United States

Cancer Center of Kansas

🇺🇸

Wichita, Kansas, United States

St. John's Hospital

🇺🇸

Saint Louis Park, Minnesota, United States

Roswell Park Cancer Institute

🇺🇸

Buffalo, New York, United States

Presbyterian Hospital Cancer Center

🇺🇸

Charlotte, North Carolina, United States

Mount Sinai Medical Center

🇺🇸

New York, New York, United States

St. Vincent Hospital / Green Bay Oncology

🇺🇸

Green Bay, Wisconsin, United States

The Miriam Hospital

🇺🇸

Providence, Rhode Island, United States

UC Davis Comprehensive Cancer Center

🇺🇸

Sacramento, California, United States

H. Lee Moffitt Cancer Center (Moffitt Cancer Center)

🇺🇸

Tampa, Florida, United States

St. Joseph Mercy Hospital

🇺🇸

Ann Arbor, Michigan, United States

University of Michigan Comprehensive Cancer Center

🇺🇸

Ann Arbor, Michigan, United States

Piedmont Hematology Oncology Associates PA

🇺🇸

Winston-Salem, North Carolina, United States

University of North Carolina at Chapel Hill

🇺🇸

Chapel Hill, North Carolina, United States

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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