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

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

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.

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 Overview

• Status: Completed
• Conditions: Neoplasm
• Intervention / Treatment: Biological: Dalotuzumab

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dalotuzumab 5 mg/kg; 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.	Biological: Dalotuzumab; IV infusion; Other Names: MK-0646
Experimental: Dalotuzumab 10 mg/kg; 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.	Biological: Dalotuzumab; IV infusion; Other Names: MK-0646
Experimental: Dalotuzumab 15 mg/kg/7.5 mg/kg; 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.	Biological: Dalotuzumab; IV infusion; Other Names: MK-0646

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Up to 71 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2008
• Primary Completion (Actual): March 18, 2009
• Study Completion (Actual): April 28, 2009

Study Registration Dates

• First Submitted: May 29, 2008
• First Submitted That Met QC Criteria: June 9, 2008
• First Posted (Estimate): June 10, 2008

Study Record Updates

• Last Update Posted (Actual): August 8, 2018
• Last Update Submitted That Met QC Criteria: July 12, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 0646-009; 2008_012 (Other Identifier: Telerex Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf