NeoplasmPhase 1NCT00694356

Study of Dalotuzumab (MK-0646) in Adults With Solid Tumors (MK-0646-009)

A Phase 1 study testing Dalotuzumab in people with Neoplasm, 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 clinical study evaluates the safety, tolerability, pharmacokinetics, and immunogenicity of dalotuzumab (MK-0646) in participants with relapsed or refractory locally advanced or metastatic solid tumors using once weekly and once every other week dose infusion regimens. Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Neoplasm
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: 15 participants
Where: No sites listed yet
Study dates: 4 Aug 2008to 28 Apr 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 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Has histologically- or cytologically-confirmed metastatic or locally advanced solid tumor(s) that has (have) failed to respond to standard therapy, or for which adequate standard therapy does not exist
Has tumor(s) associated with insulin-like growth factor 1 receptor (IGF-1R) expression in the literature (e.g. prostate, pancreatic, colon, lung and breast)
Has Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
Demonstrates adequate organ function

Who cannot join

Has had chemotherapy, radiotherapy, or biological therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration
Is concurrently using growth hormone (GH), or growth hormone inhibitor
Has any active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has any primary CNS tumor - any symptomatic ascites or plural effusion
Has a history or current evidence of any clinically significant disease that might confound the results of the study, complicate the interpretation of the study results, interfere with the participant's participation, or pose an additional risk to the participant
Is pregnant or breast-feeding

About this study

Official title: A Phase I Study of MK-0646 in Patients With Relapsed or Refractory Locally Advanced or Metastatic Solid Tumors

The primary study hypothesis is that administration of dalotuzumab as a once weekly and an every other week infusion will be generally safe and well tolerated

Conditions: Neoplasm
Being tested: Dalotuzumab
Medical subject headings: Neoplasms

What participants receive

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

DalotuzumabBiological
Also called MK-0646
IV infusion

Study groups in NCT00694356
Study group	Role	What they receive
Dalotuzumab 5 mg/kg	Experimental	Participants receive dalotuzumab 5 mg/kg by intravenous (IV) infusion once each week for up to 1 year or until participant withdraws consent, experiences an adverse event (AE), progressive disease or major protocol violation, has moved or is lost to follow up. Receives: Biological: Dalotuzumab
Dalotuzumab 10 mg/kg	Experimental	Participants receive dalotuzumab 10 mg/kg by IV infusion once each week for up to 1 year or until participant withdraws consent, experiences an AE, progressive disease or major protocol violation, has moved or is lost to follow up. Receives: Biological: Dalotuzumab
Dalotuzumab 15 mg/kg/7.5 mg/kg	Experimental	Participants receive an initial dose of dalotuzumab 15 mg/kg by IV infusion followed by a maintenance dose of dalotuzumab 7.5 mg/kg by IV infusion once every 2 weeks for up to 1 year or until participant withdraws consent, experiences an AE, progressive disease or major protocol violation, has moved or is lost to follow up. Receives: Biological: Dalotuzumab

What is being measured

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

Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
Toxicity was graded and recorded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. DLTs were defined as the occurrence of any of the following events when judged to be related to the study medication: Grade 4 neutropenia; Grade 3 neutropenia with fever >38.5°C; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity, except alopecia and inadequately treated diarrhea, nausea and vomiting. The number of participants who experienced a DLT is presented.
Measured: Cycle 1 (Up to 4 weeks)
Number of Participants Who Experienced an Adverse Event (AE)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.
Measured: Up to 30 days after last dose of study treatment (Up to 101 days)
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
Measured: Up to 71 days

Secondary outcomes (7)

Maximum Plasma Concentration (Cmax) of Dalotuzumab
Cmax was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
Measured: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Area Under the Concentration-Time Curve From Zero to Infinity (AUC0-∞) of Dalotuzumab
AUC0-∞ was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
Measured: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Time to Cmax (Tmax) of Dalotuzumab
Tmax was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
Measured: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Apparent Terminal Half-life (t1/2) of Dalotuzumab
t1/2 was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
Measured: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Clearance (CL) of Dalotuzumab
CL of dalotuzumab was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
Measured: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Steady State Volume of Distribution (Vss) of Dalotuzumab
Vss was assessed on Week 2 (Day 8) for the Dalotuzumab 5 mg/kg and Dalotuzumab 10 mg/kg treatment groups and on Week 3 (Day 15) for the Dalotuzumab 15 mg/kg/7.5 mg/kg treatment group.
Measured: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Number of Participants Who Developed a Human Anti-Humanized Antibody (HAHA) Response to Dalotuzumab
Formation of HAHAs may block efficacy by substantially increasing the clearance of dalotuzumab and limit the possibility of future dalotuzumab therapy. The occurrence of HAHAs in the sera of dalotuzumab treated participants at any of the serum collection times was assessed.
Measured: Cycle 1: predose on Days 1, 8, 15, and 22; Cycles 2 and 3: predose on Day 1; 4 weeks after last dose of study drug

Timeline

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

4 Aug 200828 Apr 2009

First posted10 Jun 2008 (estimated)
Study start4 Aug 2008
Primary completion18 Mar 2009
Study completion28 Apr 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.
Other trials for NeoplasmStudies 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: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00694356
Sponsor's protocol ID: 0646-009
Other IDs: 2008_012
Status last verified: Jul 2018
First submitted: 29 May 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

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

Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer

All Neoplasm 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: A Phase I Study of MK-0646 in Patients With Relapsed or Refractory Locally Advanced or Metastatic Solid Tumors
ClinicalTrials.gov ID: NCT00694356
Acronym / sponsor ID: 0646-009
Conditions: Neoplasm
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 4 Aug 2008 (actual)
Primary completion: 18 Mar 2009 (actual)
Study completion: 28 Apr 2009 (actual)
First posted: 10 Jun 2008 (estimated)
Results: Posted 15 Jun 2017

Clinical summary

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

The primary study hypothesis is that administration of dalotuzumab as a once weekly and an every other week infusion will be generally safe and well tolerated

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Dalotuzumab 5 mg/kg	Experimental	Biological: DalotuzumabParticipants receive dalotuzumab 5 mg/kg by intravenous (IV) infusion once each week for up to 1 year or until participant withdraws consent, experiences an adverse event (AE), progressive disease or major protocol violation, has moved or is lost to follow up.
Dalotuzumab 10 mg/kg	Experimental	Biological: DalotuzumabParticipants receive dalotuzumab 10 mg/kg by IV infusion once each week for up to 1 year or until participant withdraws consent, experiences an AE, progressive disease or major protocol violation, has moved or is lost to follow up.
Dalotuzumab 15 mg/kg/7.5 mg/kg	Experimental	Biological: DalotuzumabParticipants receive an initial dose of dalotuzumab 15 mg/kg by IV infusion followed by a maintenance dose of dalotuzumab 7.5 mg/kg by IV infusion once every 2 weeks for up to 1 year or until participant withdraws consent, experiences an AE, progressive disease or major protocol violation, has moved or is lost to follow up.

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Has histologically- or cytologically-confirmed metastatic or locally advanced solid tumor(s) that has (have) failed to respond to standard therapy, or for which adequate standard therapy does not exist
Has tumor(s) associated with insulin-like growth factor 1 receptor (IGF-1R) expression in the literature (e.g. prostate, pancreatic, colon, lung and breast)
Has Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
Demonstrates adequate organ function

Key exclusion criteria (6 listed)

Has had chemotherapy, radiotherapy, or biological therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration
Is concurrently using growth hormone (GH), or growth hormone inhibitor
Has any active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has any primary CNS tumor - any symptomatic ascites or plural effusion
Has a history or current evidence of any clinically significant disease that might confound the results of the study, complicate the interpretation of the study results, interfere with the participant's participation, or pose an additional risk to the participant

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	Biological	Dalotuzumab 10 mg/kg, Dalotuzumab 15 mg/kg/7.5 mg/kg, Dalotuzumab 5 mg/kg

Primary outcome

Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
Time frame: Cycle 1 (Up to 4 weeks)
Toxicity was graded and recorded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. DLTs were defined as the occurrence of any of the following events when judged to be related to the study medication: Grade 4 neutropenia; Grade 3 neutropenia with fever >38.5°C; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity, except alopecia and inadequately treated diarrhea, nausea and vomiting. The number of participants who experienced a DLT is presented.
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to 30 days after last dose of study treatment (Up to 101 days)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.
Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: Up to 71 days
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Any worsening (i.e. any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.

7 secondary outcomes

Maximum Plasma Concentration (Cmax) of Dalotuzumab
Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Area Under the Concentration-Time Curve From Zero to Infinity (AUC0-∞) of Dalotuzumab
Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Time to Cmax (Tmax) of Dalotuzumab
Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Apparent Terminal Half-life (t1/2) of Dalotuzumab
Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Clearance (CL) of Dalotuzumab
Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Steady State Volume of Distribution (Vss) of Dalotuzumab
Time frame: Pre-dose, 0.5 h after start of infusion, end of infusion, 5, 10, 24, 30, 48 and 96 and 168 h post-dose
Number of Participants Who Developed a Human Anti-Humanized Antibody (HAHA) Response to Dalotuzumab
Time frame: Cycle 1: predose on Days 1, 8, 15, and 22; Cycles 2 and 3: predose on Day 1; 4 weeks after last dose of study drug

Results and safety

Results posted to the registry on 15 Jun 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 5 mg/kg	3	0
Dalotuzumab 10 mg/kg	6	0
Dalotuzumab 15 mg/kg/7.5 mg/kg	6	0

Primary outcome: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

Time frame: Cycle 1 (Up to 4 weeks). Number. Unit: Participants

Measure	Dalotuzumab 5 mg/kg n = 3	Dalotuzumab 10 mg/kg n = 6	Dalotuzumab 15 mg/kg/7.5 mg/kg n = 6
Value	0	0	0

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

Primary outcome: Number of Participants Who Experienced an Adverse Event (AE)

Time frame: Up to 30 days after last dose of study treatment (Up to 101 days). Number. Unit: Participants

Measure	Dalotuzumab 5 mg/kg n = 3	Dalotuzumab 10 mg/kg n = 6	Dalotuzumab 15 mg/kg/7.5 mg/kg n = 6
Value	3	6	6

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

Primary outcome: Number of Participants Who Discontinued Study Treatment Due to an AE

Time frame: Up to 71 days. Number. Unit: Participants

Measure	Dalotuzumab 5 mg/kg n = 3	Dalotuzumab 10 mg/kg n = 6	Dalotuzumab 15 mg/kg/7.5 mg/kg n = 6
Value	1	0	0

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

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 30 days after last dose of study treatment (Up to 101 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dalotuzumab 5 mg/kg	0 of 3 (0%)	3 of 3 (100%)	Not reported
Dalotuzumab 10 mg/kg	1 of 6 (16.7%)	6 of 6 (100%)	Not reported
Dalotuzumab 15 mg/kg/7.5 mg/kg	0 of 6 (0%)	6 of 6 (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.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Related trials for Neoplasm

Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer

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 Neoplasm, 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 4 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 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 15 Jun 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?

Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) (time frame: Cycle 1 (Up to 4 weeks)). The study lists 3 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 NCT00694356.

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.