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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01507545
• Other study ID #: MORAb-004-202-CRC
• Status: Terminated
• Phase: Phase 2
• Start date: March 27, 2012
• Est. completion date: October 20, 2013

Study information

• Verified date: September 2015
• Source: Morphotek
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 154
• Est. completion date: October 20, 2013
• Est. primary completion date: October 20, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• MORAb-004
MORAb-004 8mg per kg IV once a week
• Placebo
Placebo - normal saline IV once a week

Other:
• Best supportive care
Best supportive care to improve quality of life

Locations

Country	Name	City	State
United States	Central Hem/Onc Medical Group, Inc.	Alhambra	California
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	John Hopkins University	Baltimore	Maryland
United States	Weinberg Cancer Institute at Franklin Square	Baltimore	Maryland
United States	Medcenter One	Bismarck	North Dakota
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Providence St. Joseph Medical Center-Disney Family Cancer Center	Burbank	California
United States	Lahey Clinic	Burlington	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Presbyterian Hospital Cancer Center	Charlotte	North Carolina
United States	TriHealth Oncology Institute/Oncology Partners Network	Cincinnati	Ohio
United States	Medical Oncology & Hematology Associates (Clinic #3)	Clive	Iowa
United States	Colorado Cancer Research Program	Denver	Colorado
United States	Iowa Oncology Research Association	Des Moines	Iowa
United States	Medical Oncology & Hematology Associates (Clinic #1)	Des Moines	Iowa
United States	Medical Oncology & Hematology Associates (Clinic #2)	Des Moines	Iowa
United States	Henry Ford Health System	Detroit	Michigan
United States	Essentia Health Duluth CCOP	Duluth	Minnesota
United States	Suburban Hematology-Oncology Associates, P.C.	Duluth	Georgia
United States	Duke University Medical Center	Durham	North Carolina
United States	Pharma Resource	East Providence	Rhode Island
United States	St. Jude Heritage Healthcare	Fullerton	California
United States	Medical and Surgical Specialists	Galesburg	Illinois
United States	St. Mary's Hospital Regional Cancer Center	Grand Junction	Colorado
United States	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan
United States	St. Mary's Hospital / Green Bay Oncology	Green Bay	Wisconsin
United States	St. Vincent Hospital / Green Bay Oncology	Green Bay	Wisconsin
United States	Ingalls Cancer Research Center	Harvey	Illinois
United States	Integrated Community Oncology Network / Cancer Specialists of North Florida	Jacksonville	Florida
United States	Mayo Clinic Florida Hematology/Oncology	Jacksonville	Florida
United States	CCCN	Las Vegas	Nevada
United States	Suburban Hematology-Oncology Assoc., PC	Lawrenceville	Georgia
United States	Central Baptist Hospital	Lexington	Kentucky
United States	Mount Sinai Medical Center	New York	New York
United States	Christiana Care Health Services	Newark	Delaware
United States	The Thomas and Dorothy Leavey Cancer Center Northridge Hospital Medical Center	Northridge	California
United States	Compass Research, LLC	Orange City	Florida
United States	Oncology Specialists,S.C. Center for Advanced Care	Park Ridge	Illinois
United States	Illinois CancerCare, P.C.	Peoria	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida
United States	Rhode Island Hospital	Providence	Rhode Island
United States	The Miriam Hospital	Providence	Rhode Island
United States	Mayo Clinic	Rochester	Minnesota
United States	Cancer Care Centers of Brevard	Rockledge	Florida
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	Coborn Cancer Center/ CentraCare Health Plaza	Saint Cloud	Minnesota
United States	Metro Minnesota CCOP	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Louis Park	Minnesota
United States	St. John's Hospital	Saint Louis Park	Minnesota
United States	Sharp Memorial Hospital	San Diego	California
United States	CPMCRI / Pacific Hematology Oncology Associates	San Francisco	California
United States	Central Coast Medical Oncology	Santa Maria	California
United States	UCLA Hematology Oncology	Santa Monica	California
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	Suburban Hematology-Oncology Associates, P.C.	Snellville	Georgia
United States	Hickman Cancer Center at Flower Hospital	Sylvania	Ohio
United States	H. Lee Moffitt Cancer Center (Moffitt Cancer Center)	Tampa	Florida
United States	Mercy Cancer Center	Toledo	Ohio
United States	Carle Cancer Center	Urbana	Illinois
United States	Georgetown University	Washington	District of Columbia
United States	Lutheran Hematology & Oncology	Wheat Ridge	Colorado
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Cancer Center of Kansas	Wichita	Kansas
United States	Piedmont Hematology Oncology Associates PA	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Morphotek

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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