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

A Randomized, Double-Blind, Placebo-controlled Study of the Efficacy & Safety of Monotherapy MORAb-004 Plus Best Supportive Care in Subjects With Chemorefractory Metastatic Colorectal Cancer

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

Study Overview

• Status: Terminated
• Conditions: Metastatic Colorectal Cancer; Colorectal Cancer
• Intervention / Treatment: Drug: MORAb-004; Other: Best supportive care; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Alhambra, California, United States, 91801
      • Central Hem/Onc Medical Group, Inc.
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood and Cancer Center
    • Burbank, California, United States, 91505
      • Providence St. Joseph Medical Center-Disney Family Cancer Center
    • Fullerton, California, United States, 92835
      • St. Jude Heritage Healthcare
    • Northridge, California, United States, 91328
      • The Thomas and Dorothy Leavey Cancer Center Northridge Hospital Medical Center
    • Sacramento, California, United States
      • UC Davis Comprehensive Cancer Center
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
    • San Francisco, California, United States, 94115
      • CPMCRI / Pacific Hematology Oncology Associates
    • Santa Maria, California, United States, 93454
      • Central Coast Medical Oncology
    • Santa Monica, California, United States, 90404
      • UCLA Hematology Oncology
  • Colorado
    • Denver, Colorado, United States, 80224
      • Colorado Cancer Research Program
    • Grand Junction, Colorado, United States, 81501
      • St. Mary's Hospital Regional Cancer Center
    • Wheat Ridge, Colorado, United States, 80033
      • Lutheran Hematology & Oncology
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Health Services
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida Hematology/Oncology
    • Jacksonville, Florida, United States, 32256
      • Integrated Community Oncology Network / Cancer Specialists of North Florida
    • Orange City, Florida, United States, 32763
      • Compass Research, LLC
    • Port Saint Lucie, Florida, United States, 34952
      • Hematology Oncology Associates of the Treasure Coast
    • Rockledge, Florida, United States, 32955
      • Cancer Care Centers of Brevard
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center (Moffitt Cancer Center)
  • Georgia
    • Duluth, Georgia, United States, 30096
      • Suburban Hematology-Oncology Associates, P.C.
    • Lawrenceville, Georgia, United States, 30046
      • Suburban Hematology-Oncology Assoc., PC
    • Snellville, Georgia, United States, 30078
      • Suburban Hematology-Oncology Associates, P.C.
  • Illinois
    • Galesburg, Illinois, United States, 61401
      • Medical and Surgical Specialists
    • Harvey, Illinois, United States, 60426
      • Ingalls Cancer Research Center
    • Park Ridge, Illinois, United States, 60068
      • Oncology Specialists,S.C. Center for Advanced Care
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare, P.C.
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Iowa
    • Clive, Iowa, United States, 50325
      • Medical Oncology & Hematology Associates (Clinic #3)
    • Des Moines, Iowa, United States, 50309
      • Iowa Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology & Hematology Associates (Clinic #1)
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology & Hematology Associates (Clinic #2)
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Central Baptist Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21231-1000
      • John Hopkins University
    • Baltimore, Maryland, United States, 21237
      • Weinberg Cancer Institute at Franklin Square
  • Massachusetts
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Grand Rapids, Michigan, United States, 49503
      • Grand Rapids Clinical Oncology Program
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Duluth CCOP
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center/ CentraCare Health Plaza
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro Minnesota CCOP
    • Saint Louis Park, Minnesota, United States, 55416
      • Regions Hospital
    • Saint Louis Park, Minnesota, United States, 55416
      • St. John's Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • CCCN
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
    • Charlotte, North Carolina, United States, 28204
      • Presbyterian Hospital Cancer Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27103
      • Piedmont Hematology Oncology Associates PA
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Medcenter One
  • Ohio
    • Cincinnati, Ohio, United States, 45247
      • TriHealth Oncology Institute/Oncology Partners Network
    • Sylvania, Ohio, United States, 43560
      • Hickman Cancer Center at Flower Hospital
    • Toledo, Ohio, United States, 43623
      • Mercy Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915
      • Pharma Resource
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54301
      • St. Vincent Hospital / Green Bay Oncology
    • Green Bay, Wisconsin, United States, 54303
      • St. Mary's Hospital / Green Bay Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Best supportive care; Best supportive care to improve quality of life; Drug: Placebo; Placebo - normal saline IV once a week
Active Comparator: MORAb-004	Drug: MORAb-004; MORAb-004 8mg per kg IV once a week; Other: Best supportive care; Best supportive care to improve quality of life

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	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.	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	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.	From the date of randomization to the date of death due to any cause (up to approximately 1 year 7 months)
Overall Response Rate (ORR)	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.	From the date of randomization to the first documentation of CR or PR (up to approximately 1 year 7 months)
Time to Tumor Response (TTR)	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.	From the date of randomization to first documentation of objective tumor response (CR or PR) (up to approximately 1 year 7 months)
Duration of Response (DOR)	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.	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)
Biomarkers Based PFS, Within Treatment Group	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.	From the date of randomization up to approximately 1 year 7 months
Biomarkers Based OS, Within Treatment Group	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.	From the date of randomization up to approximately 1 year 7 months

Collaborators and Investigators

• Sponsor: Morphotek

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2012
• Primary Completion (Actual): October 20, 2013
• Study Completion (Actual): October 20, 2013

Study Registration Dates

• First Submitted: December 5, 2011
• First Submitted That Met QC Criteria: January 10, 2012
• First Posted (Estimate): January 11, 2012

Study Record Updates

• Last Update Posted (Actual): May 6, 2022
• Last Update Submitted That Met QC Criteria: April 8, 2022
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: mCRC; chemorefractory metastatic colorectal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: MORAb-004-202-CRC