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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Metastatic Colorectal Cancer, Colorectal Cancer

Intervention / Treatment
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* Drug: MORAb-004
* Drug: Placebo
* Other: Best supportive care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mCRC, chemorefractory metastatic colorectal cancer