A Phase 2 interventional study of MORAb-004 and Placebo in Metastatic Colorectal Cancer and Colorectal Cancer, sponsored by Morphotek. Terminated at 67 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-05-06.
Sponsored by Morphotek (part of Eisai Co., Ltd.) · Phase 2, Interventional, and Treatment
The purpose of this study is to evaluate whether therapy with MORAb-004 is effective and safe in the treatment of metastatic, colorectal cancer.
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.
5,734 studies on the registry are indexed under Colorectal Neoplasms; 1,481 are open to participants now.
This study's enrollment of 154 is above the median of 77 across 4,222 interventional studies indexed under Colorectal Neoplasms.
Browse Colorectal Neoplasms studies →Morphotek is the lead sponsor of 21 studies on the registry; none are open to participants now.
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Exclusion Criteria:
Drug: MORAb-004 · Other: Best supportive care
Drug: Placebo · Other: Best supportive care
MORAb-004 8mg per kg IV once a week
Placebo - normal saline IV once a week
Best supportive care to improve quality of life
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.
Time frame: 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)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From the date of randomization up to approximately 1 year 7 months
Participants took part in the study at 61 investigative sites in the United States from 27 March 2012 to 20 October 2013.
| Milestone | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC |
|---|---|---|
| Started | 84 | 42 |
| Treated/safety set | 82 | 40 |
| Completed | 0 | 0 |
| Not completed | 84 | 42 |
| Withdrew: Withdrawal by subject | 6 | 2 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Discontinuation of the study by sponsor | 11 | 9 |
| Withdrew: Progressive disease | 60 | 27 |
| Withdrew: Other | 6 | 4 |
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.
| weeks | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC |
|---|---|---|
| Progression-Free Survival (PFS) | 8.1 (7.9 to 8.1) | 8.1 (8.0 to 8.3) |
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.
| months | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC |
|---|---|---|
| Overall Survival (OS) | 4.8 (3.7 to 6.2) | 6.2 (4.7 to 9.7) |
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.
| percentage of participants | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC |
|---|---|---|
| Overall Response Rate (ORR) | 0 (0.000 to 4.296) | 2.4 (0.060 to 12.566) |
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.
| weeks | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC |
|---|---|---|
| Time to Tumor Response (TTR) | — | NA (NA to NA) |
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.
| weeks | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC |
|---|---|---|
| Duration of Response (DOR) | — | NA (NA to NA) |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
Collected over From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| MORAb-004 8.0 mg/kg + BSC | 13/82 (15.9%) | 31/82 (37.8%) | 77/82 (93.9%) |
| Placebo + BSC | 4/40 (10%) | 15/40 (37.5%) | 40/40 (100%) |
| Event | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC |
|---|---|---|
| Neoplasm MalignantNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 7/82 | 2/40 |
| DehydrationMetabolism and nutrition disorders | 5/82 | 2/40 |
| PyrexiaGeneral disorders | 2/82 | 2/40 |
| Back PainMusculoskeletal and connective tissue disorders | 4/82 | 0/40 |
| Abdominal PainGastrointestinal disorders | 3/82 | 0/40 |
| Small Intestinal ObstructionGastrointestinal disorders | 3/82 | 0/40 |
| Hepatic FailureHepatobiliary disorders | 3/82 | 0/40 |
| AnaemiaBlood and lymphatic system disorders | 1/82 | 1/40 |
| ConstipationGastrointestinal disorders | 1/82 | 1/40 |
| Intestinal ObstructionGastrointestinal disorders | 1/82 | 1/40 |
| Event | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC |
|---|---|---|
| FatigueGeneral disorders | 43/82 | 19/40 |
| NauseaGastrointestinal disorders | 32/82 | 14/40 |
| Decreased AppetiteMetabolism and nutrition disorders | 28/82 | 11/40 |
| ConstipationGastrointestinal disorders | 22/82 | 13/40 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 20/82 | 9/40 |
| VomitingGastrointestinal disorders | 17/82 | 9/40 |
| CoughRespiratory, thoracic and mediastinal disorders | 12/82 | 9/40 |
| Abdominal PainGastrointestinal disorders | 16/82 | 8/40 |
| Urinary Tract InfectionInfections and infestations | 4/82 | 8/40 |
| HeadacheNervous system disorders | 16/82 | 8/40 |
Intent-to-treat (ITT) population included all randomized participants, analyzed according to the treatment assigned by the Interactive Voice Response System (IVRS) or Interactive Web Response System (IWRS).
| Age, Continuous(years) | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC | Total |
|---|---|---|---|
| Mean | 61.4 ± 11.72 | 61.8 ± 10.61 | 61.5 ± 11.32 |
| Sex: Female, Male(Participants) | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC | Total |
|---|---|---|---|
| Female | 43 | 16 | 59 |
| Male | 41 | 26 | 67 |
| Ethnicity (NIH/OMB)(Participants) | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC | Total |
|---|---|---|---|
| Hispanic or Latino | 6 | 1 | 7 |
| Not Hispanic or Latino | 75 | 40 | 115 |
| Unknown or Not Reported | 3 | 1 | 4 |
| Race (NIH/OMB)(Participants) | MORAb-004 8.0 mg/kg + BSC | Placebo + BSC | Total |
|---|---|---|---|
| American Indian or Alaska Native | 1 | 1 | 2 |
| Asian | 4 | 2 | 6 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 3 | 3 | 6 |
| White | 74 | 36 | 110 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 2 | 0 | 2 |
This study is terminated, as verified in Sep 2015. You cannot join it, but the record below documents what was studied.
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