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| ID | Type | Description | Link |
|---|---|---|---|
| MK-0646-013 | Other Identifier | Merck Registration Number | |
| 2008-004180-18 | EudraCT Number |
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A study to evaluate the response of growth factor signatures (GFS) to a single dose of dalotuzumab in participants with triple negative (TN) or estrogen receptor (ER)-positive luminal B breast cancer. The primary hypothesis is that dalotuzumab will induce a decrease in the GFS in at least 40% of participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ER-positive Luminal B | Experimental | Single dose of dalotuzumab 20 mg/kg infused intravenously over 60-120 minutes. |
|
| Triple Negative | Experimental | Single dose of dalotuzumab 20 mg/kg infused intravenously over 60-120 minutes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dalotuzumab (MK0646) | Drug | Single intravenous infusion |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Demonstrating a Decrease in the Growth Factor Signature (GFS) | GFS was measured by microarray analysis of the entire 101 gene signature expression. The GFS is quantified as the change in gene expression between two separate samples collected from the same participant. A log (base 10) ratio of expression in the post-dose sample was generated relative to the reference in both the Up and DOWN arms of the gene signature. A log ratio value of zero indicated no change in the expression between the two samples. GFS was calculated as the mean log ratio of genes in the UP arm minus mean log ratio of genes in the Down arm. GFS was compared for paired samples (pre-dose and post-dose) by a T-statistic calculated as the GFS divided by its standard error. Responders to therapy had a T-statistic that was smaller than the threshold 1st percentile of student's T-distribution and were counted as having a decrease in GFS. | Up to 12 Days Post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of IGF1R Positive Participants With a Decrease in GFS by Cohort | Insulin-like Growth Factor Receptor Type 1 (IGF1R) expression was measured in pre-dose biopsy samples using an immunohistochemistry assay to establish baseline IGF1R positivity. Biopsy samples were considered IGF1R positive if at least 10% of tumor cells stain with intensity 1+ or greater based on staining criteria of very weak (+/-); weak (1+); moderate (2+); or strong (3+). GFS response was correlated with IGF1R expression for ER-positive luminal B and triple negative cohorts. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| ID | Title | Description |
|---|---|---|
| FG000 | ER-positive Luminal B (ER+) | ER-positive Luminal B participants received a single dose of dalotuzumab 20 mg/kg infused over 60-120 minutes. |
| FG001 | Triple Negative (TN) | Triple Negative participants received a single dose of dalotuzumab 20 mg/kg infused over 60-120 minutes. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | ER-positive Luminal B (ER+) | ER-positive Luminal B participants received a single dose of dalotuzumab 20 mg/kg infused over 60-120 minutes. |
| BG001 | Triple Negative (TN) | Triple Negative participants received a single dose of dalotuzumab 20 mg/kg infused over 60-120 minutes. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants Demonstrating a Decrease in the Growth Factor Signature (GFS) | GFS was measured by microarray analysis of the entire 101 gene signature expression. The GFS is quantified as the change in gene expression between two separate samples collected from the same participant. A log (base 10) ratio of expression in the post-dose sample was generated relative to the reference in both the Up and DOWN arms of the gene signature. A log ratio value of zero indicated no change in the expression between the two samples. GFS was calculated as the mean log ratio of genes in the UP arm minus mean log ratio of genes in the Down arm. GFS was compared for paired samples (pre-dose and post-dose) by a T-statistic calculated as the GFS divided by its standard error. Responders to therapy had a T-statistic that was smaller than the threshold 1st percentile of student's T-distribution and were counted as having a decrease in GFS. | All participants who received a single dose of dalotuzumab and had evaluable baseline and post-dose biopsy samples. | Posted | Number | 80% Confidence Interval | Percentage of participants | Up to 12 Days Post-dose |
|
Up to 12 Days Post-dose
Adverse events for all participants who received a single dose of dalotuzumab
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ER-positive Luminal B (ER+) | ER-positive Luminal B participants received a single dose of dalotuzumab 20 mg/kg infused over 60-120 minutes. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| C569480 | dalotuzumab |
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| Up to 12 Days Post-dose |
| Percentage of IGF1R Negative Participants With a Decrease in GFS by Cohort | Biopsy samples were considered IGF1R negative if less than 10% of tumor cells stain. GFS response was correlated with IGF1R expression for ER-positive luminal B and triple negative cohorts. | Up to 12 Days Post-dose |
| Change From Baseline in IGF1R Membrane H-Score After a Single Dose of Dalotuzumab | IGF1R expression was measured in pre and post-dose biopsy samples using an immunohistochemistry assay. Results were expressed as an IGF1R membrane H-score. The H-score was calculated from the percentage of cells staining very weak (+/-); weak (1+); moderate (2+); or strong (3+) and obtained by the formula: (3 x percentage of strongly staining nuclei) + (2 x percentage of moderately staining nuclei) + (1 x percentage of weakly staining nuclei) + (0.5 x percentage of weakly staining nuclei). The H-score ranges from 0 to 300; with a score of 0 representing the absence of IGF1R expression and an H-score of 300 representing maximum IGF1R expression. A decrease in IGF1R membrane H-score was an indication of target engagement by dalotuzumab. A larger decrease in H-score correlated with a greater target engagement | Baseline and Up to 12 Days |
| Protocol Violation |
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| Physician Decision |
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| Withdrawal by Subject |
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| BG002 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Title |
|---|
| Description |
|---|
| OG000 | ER-positive Luminal B (ER+) | ER-positive Luminal B participants received a single dose of dalotuzumab 20 mg/kg infused over 60-120 minutes. |
| OG001 | Triple Negative (TN) | Triple Negative participants received a single dose of dalotuzumab 20 mg/kg infused over 60-120 minutes. |
|
|
| Secondary | Percentage of IGF1R Positive Participants With a Decrease in GFS by Cohort | Insulin-like Growth Factor Receptor Type 1 (IGF1R) expression was measured in pre-dose biopsy samples using an immunohistochemistry assay to establish baseline IGF1R positivity. Biopsy samples were considered IGF1R positive if at least 10% of tumor cells stain with intensity 1+ or greater based on staining criteria of very weak (+/-); weak (1+); moderate (2+); or strong (3+). GFS response was correlated with IGF1R expression for ER-positive luminal B and triple negative cohorts. | All participants who received a single dose of dalotuzumab, were IGF1R positive at baseline, and had evaluable postdose biopsy samples. | Posted | Number | 80% Confidence Interval | Percentage of participants | Up to 12 Days Post-dose |
|
|
|
| Secondary | Percentage of IGF1R Negative Participants With a Decrease in GFS by Cohort | Biopsy samples were considered IGF1R negative if less than 10% of tumor cells stain. GFS response was correlated with IGF1R expression for ER-positive luminal B and triple negative cohorts. | All participants who received a single dose of dalotuzumab, were IGF1R negative at baseline, and had evaluable postdose biopsy samples. | Posted | Number | 80% Confidence Interval | Percentage of participants | Up to 12 Days Post-dose |
|
|
|
| Secondary | Change From Baseline in IGF1R Membrane H-Score After a Single Dose of Dalotuzumab | IGF1R expression was measured in pre and post-dose biopsy samples using an immunohistochemistry assay. Results were expressed as an IGF1R membrane H-score. The H-score was calculated from the percentage of cells staining very weak (+/-); weak (1+); moderate (2+); or strong (3+) and obtained by the formula: (3 x percentage of strongly staining nuclei) + (2 x percentage of moderately staining nuclei) + (1 x percentage of weakly staining nuclei) + (0.5 x percentage of weakly staining nuclei). The H-score ranges from 0 to 300; with a score of 0 representing the absence of IGF1R expression and an H-score of 300 representing maximum IGF1R expression. A decrease in IGF1R membrane H-score was an indication of target engagement by dalotuzumab. A larger decrease in H-score correlated with a greater target engagement | All participants who received a single dose of dalotuzumab, had evaluable baseline and post-dose biopsy samples, and had H-score data available for pre- and post-dose measurements. | Posted | Mean | Full Range | H-score | Baseline and Up to 12 Days |
|
|
|
| 1 |
| 25 |
| 2 |
| 25 |
| EG001 | Triple Negative (TN) | Triple Negative participants received a single dose of dalotuzumab 20 mg/kg infused over 60-120 minutes. | 1 | 20 | 4 | 20 |
| Breast abscess | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
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| Breast cellulitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 13.0 | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
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The sponsor must review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation and can delete information identified as confidential prior to submission.
| D017437 |
| Skin and Connective Tissue Diseases |