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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00759785
First received: September 24, 2008
Last updated: March 3, 2017
Last verified: January 2017
  Purpose
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.

Condition Intervention Phase
Breast Cancer Drug: dalotuzumab (MK0646) Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Study to Establish Proof-of-Biology for MK-0646 in Breast Cancer

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants Demonstrating a Decrease in the Growth Factor Signature (GFS) [ Time Frame: 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-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.


Secondary Outcome Measures:
  • Percentage of IGF1R Positive Participants With a Decrease in GFS by Cohort [ Time Frame: 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.

  • Percentage of IGF1R Negative Participants With a Decrease in GFS by Cohort [ Time Frame: 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.

  • Change From Baseline in IGF1R Membrane H-Score After a Single Dose of Dalotuzumab [ Time Frame: 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-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


Enrollment: 48
Study Start Date: September 2008
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ER-positive Luminal B
Single dose of dalotuzumab 20 mg/kg infused intravenously over 60-120 minutes.
Drug: dalotuzumab (MK0646)
Single intravenous infusion
Other Name: MK-0646
Experimental: Triple Negative
Single dose of dalotuzumab 20 mg/kg infused intravenously over 60-120 minutes.
Drug: dalotuzumab (MK0646)
Single intravenous infusion
Other Name: MK-0646

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant has operable stage I-IIIa breast cancer of the following subtypes: (1) estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative breast cancer; (2) ER-positive tumor meeting one of the following criteria: histologic grade 3; histologic grade 2 and PR-negative; histologic grade 2 and Ki67 antigen ≥10%. Tumor is at least 2 cm in diameter as assessed by physical or radiographic exam
  • Participant is female and ≥18 years of age

Exclusion Criteria:

  • Participant is pregnant, breastfeeding or planning to become pregnant while in the study
  • Participant has received prior chemotherapy, biological therapy or radiation
  • Participant has participated in a clinical trial in the last 30 days
  • Participant has a history of drug or alcohol abuse in the last year
  • Participant is human immunodeficiency virus (HIV) positive. Patient has a history of Hepatitis B or C
  • Participant has poorly controlled diabetes mellitus
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00759785

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00759785     History of Changes
Other Study ID Numbers: 0646-013
MK-0646-013 ( Other Identifier: Merck Registration Number )
2008-004180-18 ( EudraCT Number )
Study First Received: September 24, 2008
Results First Received: November 21, 2016
Last Updated: March 3, 2017

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 19, 2017