NCT00759785

A Study of Dalotuzumab (MK-0646) in Breast Cancer Patients (MK-0646-013)

Completed Phase 1 Results posted Last updated 15 August 2018

What this trial tests

Phase 1 trial testing dalotuzumab (MK0646) in Breast Cancer in 48 participants. Completed in 17 February 2010.

Timeline

30 September 2008

Primary endpoint
17 February 2010

17 February 2010

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	48
Start date	30 September 2008
Primary completion	17 February 2010
Estimated completion	17 February 2010

Drugs / interventions tested

• dalotuzumab (MK0646) — full drug profile →

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, female only, with Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Demonstrating a Decrease in the Growth Factor Signature (GFS) Primary · Up to 12 Days Post-dose

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-d

Group	Value	95% CI
ER-positive Luminal B (ER+)	28.6	13.1 – 49.2
Triple Negative (TN)	17.6	6.7 – 35.2

Percentage of IGF1R Positive Participants With a Decrease in GFS by Cohort Secondary · Up to 12 Days Post-dose

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.

Group	Value	95% CI
ER-positive Luminal B (ER+)	25.0	9.6 – 47.5
Triple Negative (TN)	11.1	1.2 – 36.8

Percentage of IGF1R Negative Participants With a Decrease in GFS by Cohort Secondary · Up to 12 Days Post-dose

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.

Group	Value	95% CI
ER-positive Luminal B (ER+)	0.0	0.0 – 90.0
Triple Negative (TN)	20.0	2.1 – 58.4

Change From Baseline in IGF1R Membrane H-Score After a Single Dose of Dalotuzumab Secondary · Baseline and Up to 12 Days

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

Group	Value	95% CI
ER-positive Luminal B (ER+)	-104.5	-235 – -4
Triple Negative (TN)	-11.5	-105 – 100

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 12 Days Post-dose. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

ER-positive Luminal B (ER+)

Serious: 1/25 (4%)

Deaths: —

Triple Negative (TN)

Serious: 1/20 (5%)

Deaths: —

Serious adverse events (4 terms)

Reaction	System	ER-positive Luminal B (ER+)	Triple Negative (TN)
Diarrhoea	Gastrointestinal disorders	—	—
Breast abscess	Infections and infestations	—	—
Breast cellulitis	Infections and infestations	—	—
Syncope	Nervous system disorders	—	—

Other adverse events (4 terms — click to expand)

Reaction	System	ER-positive Luminal B (ER+)	Triple Negative (TN)
Nausea	Gastrointestinal disorders	—	—
Fatigue	General disorders	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—

Most-reported serious reactions: Diarrhoea, Breast abscess, Breast cellulitis, Syncope.

Data from ClinicalTrials.gov NCT00759785 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Small is beautiful: insulin-like growth factors and their role in growth, development, and cancer.
   Maki RG. · · 2010 · cited 157× · PMID 20975071 · DOI 10.1200/jco.2009.27.5040
2. Insulin-like growth factor: current concepts and new developments in cancer therapy.
   King ER, Wong KK. · · 2012 · cited 57× · PMID 21875414 · DOI 10.2174/157489212798357930
3. Comparison of TCGA and GENIE genomic datasets for the detection of clinically actionable alterations in breast cancer.
   Kaur P, Porras TB, Ring A, Carpten JD, et al · · 2019 · cited 20× · PMID 30728399 · DOI 10.1038/s41598-018-37574-8