Solid TumorPhase 1NCT00701103

Dose Escalation Trial of Dalotuzumab (MK-0646) in Advanced Solid Tumors and Multiple Myeloma (MK-0646-001)

A Phase 1 study testing Dalotuzumab in people with Solid Tumor and Multiple Myeloma, 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

This study will look for the highest tolerated dose of dalotuzumab (MK-0646) given as weekly, every other week. or a every three week infusion. The hypothesis of this study is that administration of dalotuzumab as a one- to two-hour weekly, every other week, or every three week infusion in participants with advanced… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Solid Tumor, Multiple Myeloma
What is being tested?: Dalotuzumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 80 participants
Where: No sites listed yet
Study dates: 12 Jan 2006to 1 Dec 2009
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
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Participant has metastatic or locally advanced solid tumor or multiple myeloma
Tumor specimen has IGF-1R expression
Participant agrees to use birth control throughout study

Who cannot join

Participant must not be recovering from antineoplastic therapy in the last 4 weeks
Participant has participated in a clinical trial in the last 4 weeks
Participant has a history of heart problems such as congestive heart failure, angina, heart attack or stroke in the last 3 months
Participant is taking growth hormone or growth hormone inhibitors
If female, participant is pregnant or breastfeeding
Participant is human immunodeficiency virus (HIV) positive
Participant has a history of hepatitis B or C

About this study

Official title: An Open-Label, Dose Escalation Phase I Trial of MK-0646 Given as a Once Weekly, Every Other Week, or Every Three Week Infusion in Patients With Advanced Solid Tumors and Multiple Myeloma

This study will look for the highest tolerated dose of dalotuzumab (MK-0646) given as weekly, every other week. or a every three week infusion.

The hypothesis of this study is that administration of dalotuzumab as a one- to two-hour weekly, every other week, or every three week infusion in participants with advanced cancer will be generally safe and tolerated at a dose which achieves a trough concentration ≥3 μg/mL.

Read the detailed description

Trial Duration of Treatment: Participants can be treated for up to two years if their disease has not progressed and they are not having unmanageable side effects.

Conditions: Solid Tumor, Multiple Myeloma
Being tested: Dalotuzumab
Medical subject headings: Multiple Myeloma

What participants receive

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

DalotuzumabDrug
Also called MK-0646
IV infusion

Study groups in NCT00701103
Study group	Role	What they receive
Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL)	Experimental	Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) intravenous (IV) infusion 1 time every 1 week (Q1W). Receives: Drug: Dalotuzumab
Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL)	Experimental	Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W. Receives: Drug: Dalotuzumab
Dalotuzumab 5 mg/kg Q1W (10 mg/mL)	Experimental	Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W. Receives: Drug: Dalotuzumab
Dalotuzumab 10 mg/kg Q1W (10 mg/mL)	Experimental	Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W. Receives: Drug: Dalotuzumab
Dalotuzumab 10 mg/kg Q1W (20 mg/mL)	Experimental	Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W. Receives: Drug: Dalotuzumab
Dalotuzumab 15 mg/kg Q1W (10 mg/mL)	Experimental	Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W. Receives: Drug: Dalotuzumab
Dalotuzumab 15 mg/kg Q1W (20 mg/mL)	Experimental	Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W. Receives: Drug: Dalotuzumab
Dalotuzumab 20 mg/kg Q1W (10 mg/mL)	Experimental	Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W. Receives: Drug: Dalotuzumab
Dalotuzumab 20 mg/kg Q1W (20 mg/mL)	Experimental	Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W. Receives: Drug: Dalotuzumab
Dalotuzumab 20 mg/kg Q2W (20 mg/mL)	Experimental	Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion 1 time every 2 weeks (Q2W). Receives: Drug: Dalotuzumab
Dalotuzumab 30 mg/kg Q3W (20 mg/mL)	Experimental	Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion1 time every 3 weeks (Q3W). Receives: Drug: Dalotuzumab

What is being measured

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

Percentage of Participants Who Experienced One or More Dose-limiting Toxicities (DLTs)
Toxicity was graded and recorded according to National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE 3.0). A DLT was defined as any Grade 3 or 4 toxicity. A Grade 3 toxicity was defined as severe or medically significant but not immediately life-threatening OR hospitalization or prolongation of hospitalization indicated OR disabling OR limiting self care activities of daily living. A Grade 4 toxicity was defined as: life-threatening consequences OR urgent intervention indicated. Participants were monitored for the occurrence of DLTs during the first 3 weeks of dosing with dalotuzumab.
Measured: Up to 3 weeks
Mean Terminal Half-life (t1/2) of Dalotuzumab
Terminal half-life is defined as the time it takes for the blood plasma concentration of a substance to halve (plasma half-life). Blood samples for measurement of serum levels of dalotuzumab were obtained at: pre-dose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post infusion. For infusions >1 hour in duration, an additional sample was obtained at the mid-point of the infusion. Data presented are for the harmonic mean t1/2 for dalotuzumab.
Measured: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
Area Under the Time-concentration Curve From 0 to Infinity Hours (AUC0-∞) of Dalotuzumab
AUC0-∞ represents the total drug exposure over time. Blood samples for measurement of serum levels of dalotuzumab were obtained at: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion. For infusions >1 hour in duration, an additional sample was obtained at the mid-point of the infusion.
Measured: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
Mean Serum Clearance of Dalotuzumab
Clearance is defined as the volume of serum from which study drug was completely removed per unit of time. Blood samples for measurement of serum levels of dalotuzumab were obtained at: pre-dose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post infusion. For infusions >1 hour in duration, an additional sample was obtained at the mid-point of the infusion.
Measured: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
Mean Trough Serum Concentration (Ctrough) of Dalotuzumab
The lowest (trough) concentration of dalotuzumab prior to the next dose of dalotuzumab was measured.
Measured: Pre-dose immediately prior to second infusion: 168 hours for Q1W, 336 hours for Q2W and 504 hours for Q3W dosing

Secondary outcomes (4)

Change From Baseline in Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Expression Level H-score in Skin Samples
IGF-1R expression was measured in pre- and post-dose skin biopsy samples using an immunohistochemistry (IHC) assay as a function of time and dose. Results were expressed as an IGF-1R membrane H-score which could range from 0 to 300; with a score of 0 representing the absence of IGF-1R expression and an H-score of 300 representing maximum IGF-1R expression. Changes in IGF-1R expression levels from Baseline are summarized for all participants for whom these paired data were available. A post-dose decrease in IGF-1R membrane H-score was an indication of target engagement by dalotuzumab. A larger decrease in H-score correlated with a greater target engagement.
Measured: Predose in Cycle 1 (Baseline) and predose in Cycle 3 (Week 4)
Change From Baseline in IGF-1R Protein Expression Level H-score in Tumor Samples
IGF-1R expression was measured in pre- and post-dose tumor biopsy samples using an IHC assay as a function of time and dose. Results were expressed as an IGF-1R membrane H-score which could range from 0 to 300; with a score of 0 representing the absence of IGF-1R expression and an H-score of 300 representing maximum IGF-1R expression. Changes in IGF-1R expression levels from Baseline are summarized for all participants for whom these paired data were available. A post-dose decrease in IGF-1R membrane H-score was an indication of target engagement by dalotuzumab. A larger decrease in H-score correlated with a greater target engagement.
Measured: Predose in Cycle 1 (Baseline) and predose in Cycle 3 (Week 4)
Percentage of Participants Who Developed a Serum Human-anti-humanized-antibody (HAHA) Response to Dalotuzumab
It is thought that the formation of HAHAs may block efficacy by prematurely clearing dalotuzumab and limit the possibility of future dalotuzumab therapy. Blood samples for the measurement of serum levels of HAHAs were obtained prior to treatment with dalotuzumab, and pre-dose Week 2 (Q1W), pre-dose Week 3 (Q2W), pre-dose Week 4 (QW3), pre-dose Week 5 (Q1W/Q2W), pre-dose Week 7 (Q2W/Q3W), pre-dose Week 9 (Q2W), pre-dose Week 10 (QW3) and pre-dose every 4 subsequent weeks and end of treatment (post-study: 4 weeks after last dose of study drug).
Measured: Up to 2 years
Percentage of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)
Tumor responses were measured by using Response Evaluation Criteria in Solid Tumors (RECIST) criteria in participants with solid tumors and using European Group for Blood and Marrow Transplantation (EBMT) criteria in participants with multiple myeloma. RECIST criteria for CR: Disappearance of all target lesions. RECIST criteria for PR: ≥30% decrease in the sum of diameters of target lesions. EBMT criteria for CR: Disappearance of the original mAb protein from the blood and urine AND <5% plasma cells in the bone marrow AND no increase in the size or number of lytic bone lesions AND disappearance of soft tissue plasmacytomas AND normal serum calcium levels. EMBT criteria for PR: ≥50% reduction in the serum mAb protein level AND if a urine M-component is present, a reduction in 24-hour urinary light chain excretion by either ≥90% or to <200 mg AND ≥50% reduction in the size of soft tissue plasmacytomas AND no increase in size or number of lytic bone lesions.
Measured: Up to 2 years

Timeline

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

12 Jan 20061 Dec 2009

First posted19 Jun 2008 (estimated)
Study start12 Jan 2006
Primary completion1 Dec 2009
Study completion1 Dec 2009

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Solid TumorStudies 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: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 80 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00701103
Sponsor's protocol ID: 0646-001
Other IDs: 2007_660
Status last verified: Jul 2018
First submitted: 17 Jun 2008
Last updated: 8 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

Publications

Atzori F, Tabernero J, Cervantes A, Prudkin L, Andreu J, Rodriguez-Braun E, Domingo A, Guijarro J, Gamez C, Rodon J, Di Cosimo S, Brown H, Clark J, Hardwick JS, Beckman RA, Hanley WD, Hsu K, Calvo E, Rosello S, Langdon RB, Baselga J. A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2011 Oct 1;17(19):6304-12. doi: 10.1158/1078-0432.CCR-10-3336. Epub 2011 Aug 2.
PubMed 21810918

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

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
Active, not recruitingPhase 3
A Safety and Efficacy Extension Study of Pertuzumab in Patients With Solid Tumors Previously Enrolled in a Hoffmann-La Roche-Sponsored Pertuzumab Clinical Trial
Solid Tumors
RecruitingPhase 1
IL-12 Genetically Engineered Myeloid Cells in Participants With Relapsed, Refractory Solid Tumors
Relapsed Solid Tumor Malignancies, Refractory Solid Tumor Malignancies
RecruitingObservational study
Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors
Malignant Solid Neoplasm

All Solid Tumor trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label, Dose Escalation Phase I Trial of MK-0646 Given as a Once Weekly, Every Other Week, or Every Three Week Infusion in Patients With Advanced Solid Tumors and Multiple Myeloma
ClinicalTrials.gov ID: NCT00701103
Acronym / sponsor ID: 0646-001
Conditions: Solid Tumor, Multiple Myeloma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 80 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 12 Jan 2006 (actual)
Primary completion: 1 Dec 2009 (actual)
Study completion: 1 Dec 2009 (actual)
First posted: 19 Jun 2008 (estimated)
Results: Posted 21 Mar 2017

Clinical summary

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

This study will look for the highest tolerated dose of dalotuzumab (MK-0646) given as weekly, every other week. or a every three week infusion.

Detailed description

Trial Duration of Treatment: Participants can be treated for up to two years if their disease has not progressed and they are not having unmanageable side effects.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 11

Arm	Type	Receives
Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL)	Experimental	Drug: DalotuzumabParticipants received dalotuzumab 1.25 mg/kg (10 mg/mL) intravenous (IV) infusion 1 time every 1 week (Q1W).
Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL)	Experimental	Drug: DalotuzumabParticipants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.
Dalotuzumab 5 mg/kg Q1W (10 mg/mL)	Experimental	Drug: DalotuzumabParticipants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.
Dalotuzumab 10 mg/kg Q1W (10 mg/mL)	Experimental	Drug: DalotuzumabParticipants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W.
Dalotuzumab 10 mg/kg Q1W (20 mg/mL)	Experimental	Drug: DalotuzumabParticipants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W.
Dalotuzumab 15 mg/kg Q1W (10 mg/mL)	Experimental	Drug: DalotuzumabParticipants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W.
Dalotuzumab 15 mg/kg Q1W (20 mg/mL)	Experimental	Drug: DalotuzumabParticipants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W.
Dalotuzumab 20 mg/kg Q1W (10 mg/mL)	Experimental	Drug: DalotuzumabParticipants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W.
Dalotuzumab 20 mg/kg Q1W (20 mg/mL)	Experimental	Drug: DalotuzumabParticipants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W.
Dalotuzumab 20 mg/kg Q2W (20 mg/mL)	Experimental	Drug: DalotuzumabParticipants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion 1 time every 2 weeks (Q2W).
Dalotuzumab 30 mg/kg Q3W (20 mg/mL)	Experimental	Drug: DalotuzumabParticipants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion1 time every 3 weeks (Q3W).

Who may qualify

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

Key inclusion criteria (3 listed)

Participant has metastatic or locally advanced solid tumor or multiple myeloma
Tumor specimen has IGF-1R expression
Participant agrees to use birth control throughout study

Key exclusion criteria (7 listed)

Participant must not be recovering from antineoplastic therapy in the last 4 weeks
Participant has participated in a clinical trial in the last 4 weeks
Participant has a history of heart problems such as congestive heart failure, angina, heart attack or stroke in the last 3 months
Participant is taking growth hormone or growth hormone inhibitors
If female, participant is pregnant or breastfeeding

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
DalotuzumabAlso: MK-0646IV infusion	Drug	Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL), Dalotuzumab 10 mg/kg Q1W (10 mg/mL), Dalotuzumab 10 mg/kg Q1W (20 mg/mL), Dalotuzumab 15 mg/kg Q1W (10 mg/mL), Dalotuzumab 15 mg/kg Q1W (20 mg/mL), Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL), Dalotuzumab 20 mg/kg Q1W (10 mg/mL), Dalotuzumab 20 mg/kg Q1W (20 mg/mL), Dalotuzumab 20 mg/kg Q2W (20 mg/mL), Dalotuzumab 30 mg/kg Q3W (20 mg/mL), Dalotuzumab 5 mg/kg Q1W (10 mg/mL)

Primary outcome

Percentage of Participants Who Experienced One or More Dose-limiting Toxicities (DLTs)
Time frame: Up to 3 weeks
Toxicity was graded and recorded according to National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE 3.0). A DLT was defined as any Grade 3 or 4 toxicity. A Grade 3 toxicity was defined as severe or medically significant but not immediately life-threatening OR hospitalization or prolongation of hospitalization indicated OR disabling OR limiting self care activities of daily living. A Grade 4 toxicity was defined as: life-threatening consequences OR urgent intervention indicated. Participants were monitored for the occurrence of DLTs during the first 3 weeks of dosing with dalotuzumab.
Mean Terminal Half-life (t1/2) of Dalotuzumab
Time frame: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
Terminal half-life is defined as the time it takes for the blood plasma concentration of a substance to halve (plasma half-life). Blood samples for measurement of serum levels of dalotuzumab were obtained at: pre-dose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post infusion. For infusions >1 hour in duration, an additional sample was obtained at the mid-point of the infusion. Data presented are for the harmonic mean t1/2 for dalotuzumab.
Area Under the Time-concentration Curve From 0 to Infinity Hours (AUC0-∞) of Dalotuzumab
Time frame: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
AUC0-∞ represents the total drug exposure over time. Blood samples for measurement of serum levels of dalotuzumab were obtained at: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion. For infusions >1 hour in duration, an additional sample was obtained at the mid-point of the infusion.
Mean Serum Clearance of Dalotuzumab
Time frame: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion
Clearance is defined as the volume of serum from which study drug was completely removed per unit of time. Blood samples for measurement of serum levels of dalotuzumab were obtained at: pre-dose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post infusion. For infusions >1 hour in duration, an additional sample was obtained at the mid-point of the infusion.
Mean Trough Serum Concentration (Ctrough) of Dalotuzumab
Time frame: Pre-dose immediately prior to second infusion: 168 hours for Q1W, 336 hours for Q2W and 504 hours for Q3W dosing
The lowest (trough) concentration of dalotuzumab prior to the next dose of dalotuzumab was measured.

4 secondary outcomes

Change From Baseline in Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Expression Level H-score in Skin Samples
Time frame: Predose in Cycle 1 (Baseline) and predose in Cycle 3 (Week 4)
Change From Baseline in IGF-1R Protein Expression Level H-score in Tumor Samples
Time frame: Predose in Cycle 1 (Baseline) and predose in Cycle 3 (Week 4)
Percentage of Participants Who Developed a Serum Human-anti-humanized-antibody (HAHA) Response to Dalotuzumab
Time frame: Up to 2 years
Percentage of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)
Time frame: Up to 2 years

Results and safety

Results posted to the registry on 21 Mar 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
Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL)	5	0
Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL)	3	0
Dalotuzumab 5 mg/kg Q1W (10 mg/mL)	8	0
Dalotuzumab 10 mg/kg Q1W (10 mg/mL)	6	0
Dalotuzumab 10 mg/kg Q1W (20 mg/mL)	6	0
Dalotuzumab 15 mg/kg Q1W (10 mg/mL)	6	0
Dalotuzumab 15 mg/kg Q1W (20 mg/mL)	8	0
Dalotuzumab 20 mg/kg Q1W (10 mg/mL)	7	0
Dalotuzumab 20 mg/kg Q1W (20 mg/mL)	9	0
Dalotuzumab 20 mg/kg Q2W (20 mg/mL)	11	0
Dalotuzumab 30 mg/kg Q3W (20 mg/mL)	11	0

Primary outcome: Percentage of Participants Who Experienced One or More Dose-limiting Toxicities (DLTs)

Time frame: Up to 3 weeks. Number. Unit: Percentage of Participants

Measure	Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) n = 5	Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) n = 3	Dalotuzumab 5 mg/kg Q1W (10 mg/mL) n = 8	Dalotuzumab 10 mg/kg Q1W (10 mg/mL) n = 6	Dalotuzumab 10 mg/kg Q1W (20 mg/mL) n = 6	Dalotuzumab 15 mg/kg Q1W (10 mg/mL) n = 6	Dalotuzumab 15 mg/kg Q1W (20 mg/mL) n = 8	Dalotuzumab 20 mg/kg Q1W (10 mg/mL) n = 7	Dalotuzumab 20 mg/kg Q1W (20 mg/mL) n = 9	Dalotuzumab 20 mg/kg Q2W (20 mg/mL) n = 11	Dalotuzumab 30 mg/kg Q3W (20 mg/mL) n = 11
Value	0	0	13	0	0	0	0	0	0	0	0

Population analysed: The population consisted of all participants who received at least one dose of study drug.

Primary outcome: Mean Terminal Half-life (t1/2) of Dalotuzumab

Time frame: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion. Mean (Full Range). Unit: Hours

Measure	Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) n = 5	Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) n = 3	Dalotuzumab 5 mg/kg Q1W (10 mg/mL) n = 8	Dalotuzumab 10 mg/kg Q1W (10 mg/mL) n = 6	Dalotuzumab 10 mg/kg Q1W (20 mg/mL) n = 3	Dalotuzumab 15 mg/kg Q1W (10 mg/mL) n = 6	Dalotuzumab 15 mg/kg Q1W (20 mg/mL) n = 8	Dalotuzumab 20 mg/kg Q1W (10 mg/mL) n = 7	Dalotuzumab 20 mg/kg Q1W (20 mg/mL) n = 9	Dalotuzumab 20 mg/kg Q2W (20 mg/mL) n = 11	Dalotuzumab 30 mg/kg Q3W (20 mg/mL) n = 11
Value	67 (46 to 121)	79 (53 to 113)	83 (41 to 240)	169 (134 to 265)	100 (81 to 123)	95 (43 to 165)	110 (83 to 215)	129 (74 to 240)	120 (66 to 184)	106 (44 to 134)	142 (73 to 187)

Population analysed: The population consisted of all evaluable participants who received \>90% of intended drug volume and had t1/2 pharmacokinetic measurements at Baseline and at least once during treatment.

Primary outcome: Area Under the Time-concentration Curve From 0 to Infinity Hours (AUC0-∞) of Dalotuzumab

Time frame: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion. Mean (Standard Deviation). Unit: mg*hr/mL

Measure	Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) n = 5	Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) n = 3	Dalotuzumab 5 mg/kg Q1W (10 mg/mL) n = 8	Dalotuzumab 10 mg/kg Q1W (10 mg/mL) n = 6	Dalotuzumab 10 mg/kg Q1W (20 mg/mL) n = 3	Dalotuzumab 15 mg/kg Q1W (10 mg/mL) n = 6	Dalotuzumab 15 mg/kg Q1W (20 mg/mL) n = 8	Dalotuzumab 20 mg/kg Q1W (10 mg/mL) n = 7	Dalotuzumab 20 mg/kg Q1W (20 mg/mL) n = 9	Dalotuzumab 20 mg/kg Q2W (20 mg/mL) n = 11	Dalotuzumab 30 mg/kg Q3W (20 mg/mL) n = 11
Value	1.6 (0.4)	3.7 (1.1)	12.9 (4.4)	28.9 (10.4)	18.4 (4.1)	39.4 (14.5)	28.8 (8.8)	52.7 (19.2)	44.3 (20.0)	45.9 (14.4)	92.6 (29.8)

Population analysed: The population consisted of all evaluable participants who received \>90% of intended drug volume and had AUC0-last pharmacokinetic measurements at Baseline and at least once during treatment.

Primary outcome: Mean Serum Clearance of Dalotuzumab

Time frame: Predose; pre-end infusion; 0.5, 5, 10, 24, 30 (Q1W only), 48, 96, 168 (Q2W/Q3W only), 336 (Q3W only) hours post-infusion. Mean (Standard Deviation). Unit: mL/min/kg

Measure	Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL) n = 5	Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL) n = 3	Dalotuzumab 5 mg/kg Q1W (10 mg/mL) n = 8	Dalotuzumab 10 mg/kg Q1W (10 mg/mL) n = 6	Dalotuzumab 10 mg/kg Q1W (20 mg/mL) n = 3	Dalotuzumab 15 mg/kg Q1W (10 mg/mL) n = 6	Dalotuzumab 15 mg/kg Q1W (20 mg/mL) n = 8	Dalotuzumab 20 mg/kg Q1W (10 mg/mL) n = 7	Dalotuzumab 20 mg/kg Q1W (20 mg/mL) n = 9	Dalotuzumab 20 mg/kg Q2W (20 mg/mL) n = 11	Dalotuzumab 30 mg/kg Q3W (20 mg/mL) n = 11
Value	0.013 (0.004)	0.012 (0.003)	0.007 (0.003)	0.006 (0.002)	0.009 (0.002)	0.007 (0.004)	0.010 (0.004)	0.007 (0.003)	0.009 (0.004)	0.008 (0.003)	0.006 (0.003)

Population analysed: The population consisted of all evaluable participants who received \>90% of intended drug volume and had mean serum clearance pharmacokinetic measurements at Baseline and at least once during treatment.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 30 days after last dose of study drug (Up to 25 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL)	0 of 5 (0%)	5 of 5 (100%)	Not reported
Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL)	0 of 3 (0%)	3 of 3 (100%)	Not reported
Dalotuzumab 5 mg/kg Q1W (10 mg/mL)	2 of 8 (25%)	6 of 8 (75%)	Not reported
Dalotuzumab 10 mg/kg Q1W (10 mg/mL)	2 of 6 (33.3%)	5 of 6 (83.3%)	Not reported
Dalotuzumab 10 mg/kg Q1W (20 mg/mL)	2 of 6 (33.3%)	4 of 6 (66.7%)	Not reported
Dalotuzumab 15 mg/kg Q1W (10 mg/mL)	3 of 6 (50%)	5 of 6 (83.3%)	Not reported
Dalotuzumab 15 mg/kg Q1W (20 mg/mL)	3 of 8 (37.5%)	8 of 8 (100%)	Not reported
Dalotuzumab 20 mg/kg Q1W (10 mg/mL)	0 of 7 (0%)	6 of 7 (85.7%)	Not reported
Dalotuzumab 20 mg/kg Q1W (20 mg/mL)	2 of 9 (22.2%)	8 of 9 (88.9%)	Not reported
Dalotuzumab 20 mg/kg Q2W (20 mg/mL)	3 of 11 (27.3%)	9 of 11 (81.8%)	Not reported
Dalotuzumab 30 mg/kg Q3W (20 mg/mL)	1 of 11 (9.1%)	11 of 11 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21810918Atzori F, Tabernero J, Cervantes A, Prudkin L, Andreu J, Rodriguez-Braun E, Domingo A, Guijarro J, Gamez C, Rodon J, Di Cosimo S, Brown H, Clark J, Hardwick JS, Beckman RA, Hanley WD, Hsu K, Calvo E, Rosello S, Langdon RB, Baselga J. A phase I pharmacokinetic and pharmacodynamic study of dalotuzumab (MK-0646), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res. 2011 Oct 1;17(19):6304-12. doi: 10.1158/1078-0432.CCR-10-3336. Epub 2011 Aug 2.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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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 in people with Solid Tumor and Multiple Myeloma, 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 3 inclusion and 7 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 8 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 21 Mar 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 Who Experienced One or More Dose-limiting Toxicities (DLTs) (time frame: Up to 3 weeks). The study lists 5 primary outcomes in all. 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 NCT00701103, which also lists 1 linked publication.

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 8 Aug 2018.