Skip to content
Triangle logo TriangleGet started
← Study library

NCT00701103 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1
Status at capture
COMPLETED
Registry last update
2018-08-08

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

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

→

outcome · POSTED

Mean Serum Clearance of Dalotuzumab

→

outcome · POSTED

Mean Trough Serum Concentration (Ctrough) of Dalotuzumab

→

outcome · POSTED

Change From Baseline in Insulin-like Growth Factor Receptor Type 1 (IGF-1R) Protein Expression Level H-score in Skin Samples

→

outcome · POSTED

Change From Baseline in IGF-1R Protein Expression Level H-score in Tumor Samples

→

outcome · POSTED

Percentage of Participants Who Developed a Serum Human-anti-humanized-antibody (HAHA) Response to Dalotuzumab

→

outcome · POSTED

Percentage of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→
Who could take part
eligibility Criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Participants received dalotuzumab 1.25 mg/kg (10 mg/mL) intravenous (IV) infusion 1 time every 1 week (Q1W).
    intervention Names
    1. Drug: Dalotuzumab
    label
    Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL)
    type
    EXPERIMENTAL
  2. description
    Participants received dalotuzumab 2.5 mg/kg (10 mg/mL) IV infusion Q1W.
    intervention Names
    1. Drug: Dalotuzumab
    label
    Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL)
    type
    EXPERIMENTAL
  3. description
    Participants received dalotuzumab 5 mg/kg (10 mg/mL) IV infusion Q1W.
    intervention Names
    1. Drug: Dalotuzumab
    label
    Dalotuzumab 5 mg/kg Q1W (10 mg/mL)
    type
    EXPERIMENTAL
  4. description
    Participants received dalotuzumab 10 mg/kg (10 mg/mL) IV infusion Q1W.
    intervention Names
    1. Drug: Dalotuzumab
    label
    Dalotuzumab 10 mg/kg Q1W (10 mg/mL)
    type
    EXPERIMENTAL
  5. description
    Participants received dalotuzumab 10 mg/kg (20 mg/mL) IV infusion Q1W.
    intervention Names
    1. Drug: Dalotuzumab
    label
    Dalotuzumab 10 mg/kg Q1W (20 mg/mL)
    type
    EXPERIMENTAL
  6. description
    Participants received dalotuzumab 15 mg/kg (10 mg/mL) IV infusion Q1W.
    intervention Names
    1. Drug: Dalotuzumab
    label
    Dalotuzumab 15 mg/kg Q1W (10 mg/mL)
    type
    EXPERIMENTAL
  7. description
    Participants received dalotuzumab 15 mg/kg (20 mg/ mL) IV infusion Q1W.
    intervention Names
    1. Drug: Dalotuzumab
    label
    Dalotuzumab 15 mg/kg Q1W (20 mg/mL)
    type
    EXPERIMENTAL
  8. description
    Participants received dalotuzumab 20 mg/kg (10 mg/mL) IV infusion Q1W.
    intervention Names
    1. Drug: Dalotuzumab
    label
    Dalotuzumab 20 mg/kg Q1W (10 mg/mL)
    type
    EXPERIMENTAL
  9. description
    Participants received dalotuzumab 20.0 mg/kg (20 mg/mL) IV infusion Q1W.
    intervention Names
    1. Drug: Dalotuzumab
    label
    Dalotuzumab 20 mg/kg Q1W (20 mg/mL)
    type
    EXPERIMENTAL
  10. description
    Participants received dalotuzumab 20 mg/kg (20 mg/mL) IV infusion 1 time every 2 weeks (Q2W).
    intervention Names
    1. Drug: Dalotuzumab
    label
    Dalotuzumab 20 mg/kg Q2W (20 mg/mL)
    type
    EXPERIMENTAL
  11. description
    Participants received dalotuzumab 30 mg/kg (20 mg/mL) IV infusion1 time every 3 weeks (Q3W).
    intervention Names
    1. Drug: Dalotuzumab
    label
    Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Dalotuzumab 1.25 mg/kg Q1W (10 mg/mL)
    2. Dalotuzumab 10 mg/kg Q1W (10 mg/mL)
    3. Dalotuzumab 10 mg/kg Q1W (20 mg/mL)
    4. Dalotuzumab 15 mg/kg Q1W (10 mg/mL)
    5. Dalotuzumab 15 mg/kg Q1W (20 mg/mL)
    6. Dalotuzumab 2.5 mg/kg Q1W (10 mg/mL)
    7. Dalotuzumab 20 mg/kg Q1W (10 mg/mL)
    8. Dalotuzumab 20 mg/kg Q1W (20 mg/mL)
    9. Dalotuzumab 20 mg/kg Q2W (20 mg/mL)
    10. Dalotuzumab 30 mg/kg Q3W (20 mg/mL)
    11. Dalotuzumab 5 mg/kg Q1W (10 mg/mL)
    description
    IV infusion
    name
    Dalotuzumab
    other Names
    1. MK-0646
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
80
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Percentage of Participants Who Experienced One or More Dose-limiting Toxicities (DLTs)
    time Frame
    Up to 3 weeks
  2. description
    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.
    measure
    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
  3. description
    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.
    measure
    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
  4. description
    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.
    measure
    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
  5. description
    The lowest (trough) concentration of dalotuzumab prior to the next dose of dalotuzumab was measured.
    measure
    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
secondary Outcomes
  1. description
    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.
    measure
    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)
  2. description
    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.
    measure
    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)
  3. description
    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).
    measure
    Percentage of Participants Who Developed a Serum Human-anti-humanized-antibody (HAHA) Response to Dalotuzumab
    time Frame
    Up to 2 years
  4. description
    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.
    measure
    Percentage of Participants Who Experienced a Complete Response (CR) or Partial Response (PR)
    time Frame
    Up to 2 years
Full study description
brief 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 cancer will be generally safe and tolerated at a dose which achieves a trough concentration ≥3 μg/mL.
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.
Source references
references
  1. citation
    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.
    pmid
    21810918
    type
    RESULT
Source notices and limitations
    Discovery and provenance
    1. release id
      ctgov-registry-1336d216cbd1bbff780dac70
      edge id
      nct-edge-514894a5961c67eacedc
      requested nct id
      NCT00701103
      primary nct id
      NCT00701103
      source kind
      ctgov_condition_query
      source record id
      Source null
      source file sha256
      2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
      payload sha256
      952f9df34f1061ea736a0a28c0517d0aea3c6aa2008e6fa6d80f1ceea5bfa737
      payload
      clinical indication matching status
      condition_index_match_asserted_by_registry_not_reviewed
      end exclusive
      true
      id
      nct-edge-514894a5961c67eacedc
      link basis
      returned_by_explicit_condition_and_posted_results_filter_query
      nct id
      NCT00701103
      occurrences
      1. context exact
        NCT00701103
        end
        11
        exact text
        NCT00701103
        start
        0
      offset unit
      unicode_code_points
      query cond
      Plasma Cell Neoplasms
      query disease state id
      ds-plasma-cell-neoplasms
      source file
      /Users/arunverma/Documents/ChatGPT/Cancer Statistics Website/research-data/2026-09-10/clinicaltrials-condition/round-0000/raw/cond-plasma-cell-neoplasms-000.json
      source file sha256
      2314ce01316b2d7044d298c6d25eda12e99cc5f44273bc75efed6cd5e03a8c14
      source json pointer
      /studies/469/protocolSection/identificationModule/nctId
      source kind
      ctgov_condition_query
      source record id
      Source null
      source string basis
      parsed_JSON_string_unmodified
      source string sha256
      b16ca71d0d2286ed7b9fc1f5727cd78edc18706dd94bd360a10d29a9e9735de5

    Preserved source evidence · Not medical advice