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

A Phase 1 study testing dalotuzumab (MK0646) in people with Breast Cancer, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Cancer
What is being tested?: dalotuzumab (MK0646)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 48 participants
Where: No sites listed yet
Study dates: 30 Sep 2008to 17 Feb 2010
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

About this study

Official title: A Study to Establish Proof-of-Biology for MK-0646 in Breast Cancer

Conditions: Breast Cancer
Being tested: dalotuzumab (MK0646)
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

dalotuzumab (MK0646)Drug
Also called MK-0646
Single intravenous infusion

Study groups in NCT00759785
Study group	Role	What they receive
ER-positive Luminal B	Experimental	Single dose of dalotuzumab 20 mg/kg infused intravenously over 60-120 minutes. Receives: Drug: dalotuzumab (MK0646)
Triple Negative	Experimental	Single dose of dalotuzumab 20 mg/kg infused intravenously over 60-120 minutes. Receives: Drug: dalotuzumab (MK0646)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Up to 12 Days Post-dose

Secondary outcomes (3)

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.
Measured: 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.
Measured: 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
Measured: Baseline and Up to 12 Days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Sep 200817 Feb 2010

First posted25 Sep 2008 (estimated)
Study start30 Sep 2008
Primary completion17 Feb 2010
Study completion17 Feb 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00759785
Sponsor's protocol ID: 0646-013
Other IDs: MK-0646-013, 2008-004180-18, 2008
Status last verified: Jul 2018
First submitted: 24 Sep 2008
Last updated: 15 Aug 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

All Breast Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study to Establish Proof-of-Biology for MK-0646 in Breast Cancer
ClinicalTrials.gov ID: NCT00759785
Acronym / sponsor ID: 0646-013
Conditions: Breast Cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 30 Sep 2008 (actual)
Primary completion: 17 Feb 2010 (actual)
Study completion: 17 Feb 2010 (actual)
First posted: 25 Sep 2008 (estimated)
Results: Posted 14 Apr 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
ER-positive Luminal B	Experimental	Drug: dalotuzumab (MK0646)Single dose of dalotuzumab 20 mg/kg infused intravenously over 60-120 minutes.
Triple Negative	Experimental	Drug: dalotuzumab (MK0646)Single dose of dalotuzumab 20 mg/kg infused intravenously over 60-120 minutes.

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
dalotuzumab (MK0646)Also: MK-0646Single intravenous infusion	Drug	ER-positive Luminal B, Triple Negative

Primary outcome

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.

3 secondary outcomes

Percentage of IGF1R Positive Participants With a Decrease in GFS by Cohort
Time frame: Up to 12 Days Post-dose
Percentage of IGF1R Negative Participants With a Decrease in GFS by Cohort
Time frame: Up to 12 Days Post-dose
Change From Baseline in IGF1R Membrane H-Score After a Single Dose of Dalotuzumab
Time frame: Baseline and Up to 12 Days

Results and safety

Results posted to the registry on 14 Apr 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ER-positive Luminal B (ER+)	26	14
Triple Negative (TN)	22	17

Primary outcome: Percentage of Participants Demonstrating a Decrease in the Growth Factor Signature (GFS)

Time frame: Up to 12 Days Post-dose. Number (80% Confidence Interval). Unit: Percentage of participants

Measure	ER-positive Luminal B (ER+) n = 14	Triple Negative (TN) n = 17
Value	28.6 (13.1 to 49.2)	17.6 (6.7 to 35.2)

Population analysed: All participants who received a single dose of dalotuzumab and had evaluable baseline and post-dose biopsy samples.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 12 Days Post-dose. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
ER-positive Luminal B (ER+)	1 of 25 (4%)	2 of 25 (8%)	Not reported
Triple Negative (TN)	1 of 20 (5%)	4 of 20 (20%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Related trials for Breast Cancer

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing dalotuzumab (MK0646) in people with Breast Cancer, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Demonstrating a Decrease in the Growth Factor Signature (GFS) (time frame: Up to 12 Days Post-dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00759785.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2018.