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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00694356
First Posted: June 10, 2008
Last Update Posted: June 15, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
  Purpose

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


Condition Intervention Phase
Neoplasm Biological: Dalotuzumab Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of MK-0646 in Patients With Relapsed or Refractory Locally Advanced or Metastatic Solid Tumors

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

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]
    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.

  • 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 ]
    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.

  • 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 ]
    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.

  • 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 ]
    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.

  • 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 ]
    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.

  • 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 ]
    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.

  • 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 ]
    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.


Enrollment: 15
Study Start Date: August 4, 2008
Study Completion Date: April 28, 2009
Primary Completion Date: March 18, 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: MK-0646

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00694356


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: NCT00694356     History of Changes
Other Study ID Numbers: 0646-009
2008_012 ( Other Identifier: Telerex Study Number )
First Submitted: May 29, 2008
First Posted: June 10, 2008
Results First Submitted: March 28, 2017
Results First Posted: June 15, 2017
Last Update Posted: June 15, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs