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A Study to Determine the Activity of Robatumumab (SCH 717454, MK-7454) in Participants With Relapsed or Recurrent Colorectal Cancer (P04721, MK-7454-003)

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Robatumumab
Irinotecan
Cetuximab
Capecitabine
FOLFOX
CAPEOX/XELOX
FOLFIRI
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring anti-IGF-1R

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Older than 18 years of age, of any race, and gender;
  • Diagnosis of histologically confirmed relapsed or recurrent colorectal carcinoma that has progressed on at least first-line therapy;
  • Must have a computed tomography (CT) or magnetic resonance imaging (MRI) scan performed at some point during their immediate prior treatment or observation in order to determine tumor growth rate;
  • Must have measurable disease on a CT or MRI study, performed during Screening;
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status of <=2 and a minimum life expectancy of ≥4 months;
  • Must have adequate organ function within 3 weeks prior to treatment assignment

Exclusion Criteria:

  • History of another malignancy;
  • Known treated or untreated leptomeningeal metastasis, or a metastatic central nervous system lesion;
  • Surgery within 3 weeks;
  • Radiation therapy within 6 weeks;
  • A history of uncontrolled diabetes mellitus, defined as a hemoglobin A1C of >7.5% in a participant with known diabetes mellitus;
  • A recent myocardial infarction (within the past year); or a participant who at the time of Screening presents with unstable or uncontrolled angina, New York Heart Association Class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram abnormality;
  • An active infection;
  • Has clinically significant hepatitis at Screening, or is hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Robatumumab→Robatumumab

    Chemotherapy→Robatumumab

    Arm Description

    Participants receive 1 dose of robatumumab 0.3 mg/kg intravenously (IV) followed by 1 dose of robatumumab 10 mg/kg IV once every 2 weeks (Q2W) until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.

    Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.

    Outcomes

    Primary Outcome Measures

    Number of Participants With a >20% Decrease in Positron Emission Tomography (PET)-Assessed Tumor Glucose Metabolism: Fluorodeoxyglucose (FDG) Standardized Uptake Value (SUV) in the Target Lesion
    FDG-PET was used in this study to detect the biological activity of modulation of the target within the tumor. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 was used to select the target lesion. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs were identified as target lesions and recorded and measured at Baseline. The changes in SUVmax were calculated using the formula: (endpoint SUVmax - baseline SUVmax)/baseline SUVmax as a percentage. If multiple lesions had been measured at a visit, percentages calculated for all target lesions were averaged to find the decrease during the treatment period per participant. FDG SUVmax responder was defined as participants with >20% decrease in SUVmax after the first cycle of robatumumab in Period 2.

    Secondary Outcome Measures

    Number of Participants Who Experienced One or More Adverse Events (AEs)
    An AE is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the study drug. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
    Best Overall Tumor Response Per Investigator Review
    Tumor response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) scans using RECIST v 1.0 criteria at Screening, at every 8 weeks of robatumumab treatment during Period 2 and at post study. A sum of the longest diameter (LD) for all target lesions was calculated and reported as the baseline sum LD. Overall tumor responses were defined as: Complete Response (CR) - Disappearance of all target lesions; Partial Response (PR) - At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or Stable Disease (SD) - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
    Number of Participants Who Discontinued Study Drug Due to an AE
    An AE is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the study drug. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
    Best Overall Tumor Response Per Central Review
    Tumor response was assessed by CT or MRI scan using RECIST v1.0 criteria at Screening, at every 8 weeks of robatumumab treatment during Period 2 and at post study. A sum of the LD for all target lesions was calculated and reported as the baseline sum LD. Overall tumor responses were defined as: Complete Response (CR) - Disappearance of all target lesions; Partial Response (PR) - At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or Stable Disease (SD) - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
    Change From Baseline in Tumor Growth Rate
    Tumor growth rate was assessed by CT or MRI scans using RECIST criteria at Screening, at every 8 weeks of robatumumab treatment and at post study. For Pre Baseline 1, tumor growth rate=(sum of longest diameter of target lesions at Baseline - the most recent prior to Baseline)/duration between Baseline and Pre Baseline. For all other cycles, tumor growth rate=(sum of longest diameter of target lesions at a cycle - Baseline)/ duration between Baseline and the cycle. The cycles presented below are relative to the first dose of robatumumab in Period 1.

    Full Information

    First Posted
    October 29, 2007
    Last Updated
    July 25, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00551213
    Brief Title
    A Study to Determine the Activity of Robatumumab (SCH 717454, MK-7454) in Participants With Relapsed or Recurrent Colorectal Cancer (P04721, MK-7454-003)
    Official Title
    A Fixed-Sequence, Open-Label Study to Determine the Activity of SCH 717454 as Assessed by Positron Emission Tomography in Subjects With Relapsed or Recurrent Colorectal Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    November 21, 2007 (Actual)
    Primary Completion Date
    June 4, 2009 (Actual)
    Study Completion Date
    June 4, 2009 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study was to determine the activity of two doses of robatumumab (SCH 717454, MK-7454) in participants with relapsed or recurrent colorectal cancer. The primary study hypothesis was that decreases in Positron Emission Tomography (PET)-assessed tumor glucose metabolism (i.e., fluorodeoxyglucose [FDG] standardized uptake value [SUV]) following administration of 10 mg/kg robatumumab will exceed those following administration of 0.3 mg/kg robatumumab in participants with relapsed or recurrent colorectal cancer who had progressed after first-line chemotherapy. Investigator choices of standard chemotherapy: irinotecan as a single agent +/- cetuximab OR capecitabine as a single agent, OR FOLFOX (leucovorin calcium [folinic acid][FOL] + fluorouracil [F] + oxaliplatin [OX]) OR CAPEO(capecitabine [CAPE] or Xeloda® [XEL] + oxaliplatin [OX]) OR FOLFIRI (leucovorin calcium [folinic acid][FOL] + fluorouracil [F] + irinotecan [IRI]) +/- cetuximab OR cetuximab as a single agent.
    Detailed Description
    Standard chemotherapy was used as a positive validation arm. Randomization was performed so that there could be no bias in the selection of participants for enrollment into the fixed-sequence arms. Once three chemotherapy-treated participants demonstrated decreases in FDG-PET SUV in the target lesion (i.e., >20% decrease in SUVmax in the defined target lesion) in the PET/computed tomography (CT) scan performed following Cycle 1 Period 1 treatment, it was concluded that this positive validation arm had accomplished its purpose, and all subsequent participants enrolled in the study were assigned treatment with robatumumab for Period 1. There was no intention to compare the data in either period across participants who received chemotherapy with those who received robatumumab.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Colorectal Cancer
    Keywords
    anti-IGF-1R

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    67 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Robatumumab→Robatumumab
    Arm Type
    Experimental
    Arm Description
    Participants receive 1 dose of robatumumab 0.3 mg/kg intravenously (IV) followed by 1 dose of robatumumab 10 mg/kg IV once every 2 weeks (Q2W) until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.
    Arm Title
    Chemotherapy→Robatumumab
    Arm Type
    Active Comparator
    Arm Description
    Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.
    Intervention Type
    Biological
    Intervention Name(s)
    Robatumumab
    Intervention Type
    Drug
    Intervention Name(s)
    Irinotecan
    Intervention Type
    Biological
    Intervention Name(s)
    Cetuximab
    Intervention Type
    Drug
    Intervention Name(s)
    Capecitabine
    Intervention Type
    Drug
    Intervention Name(s)
    FOLFOX
    Intervention Description
    Leucovorin calcium (folinic acid)(FOL) + 5-fluorouracil (F)+ oxaliplatin (OX)
    Intervention Type
    Drug
    Intervention Name(s)
    CAPEOX/XELOX
    Intervention Description
    Capecitabine (CAPE) or Xeloda® (XEL) + oxaliplatin (OX)
    Intervention Type
    Drug
    Intervention Name(s)
    FOLFIRI
    Intervention Description
    Leucovorin calcium (folinic acid)(FOL) + 5-fluorouracil (F)+ irinotecan (IRI)
    Primary Outcome Measure Information:
    Title
    Number of Participants With a >20% Decrease in Positron Emission Tomography (PET)-Assessed Tumor Glucose Metabolism: Fluorodeoxyglucose (FDG) Standardized Uptake Value (SUV) in the Target Lesion
    Description
    FDG-PET was used in this study to detect the biological activity of modulation of the target within the tumor. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 was used to select the target lesion. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs were identified as target lesions and recorded and measured at Baseline. The changes in SUVmax were calculated using the formula: (endpoint SUVmax - baseline SUVmax)/baseline SUVmax as a percentage. If multiple lesions had been measured at a visit, percentages calculated for all target lesions were averaged to find the decrease during the treatment period per participant. FDG SUVmax responder was defined as participants with >20% decrease in SUVmax after the first cycle of robatumumab in Period 2.
    Time Frame
    After the first robatumumab dose in Period 2 (Up to approximately 4 weeks after first robatumumab dose in Period 1)
    Secondary Outcome Measure Information:
    Title
    Number of Participants Who Experienced One or More Adverse Events (AEs)
    Description
    An AE is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the study drug. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
    Time Frame
    Up to 30 days after last dose of study drug (Up to approximately 22 weeks)
    Title
    Best Overall Tumor Response Per Investigator Review
    Description
    Tumor response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI) scans using RECIST v 1.0 criteria at Screening, at every 8 weeks of robatumumab treatment during Period 2 and at post study. A sum of the longest diameter (LD) for all target lesions was calculated and reported as the baseline sum LD. Overall tumor responses were defined as: Complete Response (CR) - Disappearance of all target lesions; Partial Response (PR) - At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or Stable Disease (SD) - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
    Time Frame
    Up to 30 days after last dose of study drug (Up to approximately 22 weeks)
    Title
    Number of Participants Who Discontinued Study Drug Due to an AE
    Description
    An AE is any untoward medical occurrence in a participant administered study drug which does not necessarily have a causal relationship with the study drug. AEs may include the onset of new illness and the exacerbation of pre-existing conditions.
    Time Frame
    Up to last dose of study drug (Up to approximately 18 weeks)
    Title
    Best Overall Tumor Response Per Central Review
    Description
    Tumor response was assessed by CT or MRI scan using RECIST v1.0 criteria at Screening, at every 8 weeks of robatumumab treatment during Period 2 and at post study. A sum of the LD for all target lesions was calculated and reported as the baseline sum LD. Overall tumor responses were defined as: Complete Response (CR) - Disappearance of all target lesions; Partial Response (PR) - At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or Stable Disease (SD) - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
    Time Frame
    Up to 30 days after last dose of study drug (Up to approximately 22 weeks)
    Title
    Change From Baseline in Tumor Growth Rate
    Description
    Tumor growth rate was assessed by CT or MRI scans using RECIST criteria at Screening, at every 8 weeks of robatumumab treatment and at post study. For Pre Baseline 1, tumor growth rate=(sum of longest diameter of target lesions at Baseline - the most recent prior to Baseline)/duration between Baseline and Pre Baseline. For all other cycles, tumor growth rate=(sum of longest diameter of target lesions at a cycle - Baseline)/ duration between Baseline and the cycle. The cycles presented below are relative to the first dose of robatumumab in Period 1.
    Time Frame
    Baseline and up to approximately 22 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Older than 18 years of age, of any race, and gender; Diagnosis of histologically confirmed relapsed or recurrent colorectal carcinoma that has progressed on at least first-line therapy; Must have a computed tomography (CT) or magnetic resonance imaging (MRI) scan performed at some point during their immediate prior treatment or observation in order to determine tumor growth rate; Must have measurable disease on a CT or MRI study, performed during Screening; Must have an Eastern Cooperative Oncology Group (ECOG) performance status of <=2 and a minimum life expectancy of ≥4 months; Must have adequate organ function within 3 weeks prior to treatment assignment Exclusion Criteria: History of another malignancy; Known treated or untreated leptomeningeal metastasis, or a metastatic central nervous system lesion; Surgery within 3 weeks; Radiation therapy within 6 weeks; A history of uncontrolled diabetes mellitus, defined as a hemoglobin A1C of >7.5% in a participant with known diabetes mellitus; A recent myocardial infarction (within the past year); or a participant who at the time of Screening presents with unstable or uncontrolled angina, New York Heart Association Class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram abnormality; An active infection; Has clinically significant hepatitis at Screening, or is hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    24905030
    Citation
    Lin EH, Lenz HJ, Saleh MN, Mackenzie MJ, Knost JA, Pathiraja K, Langdon RB, Yao SL, Lu BD. A randomized, phase II study of the anti-insulin-like growth factor receptor type 1 (IGF-1R) monoclonal antibody robatumumab (SCH 717454) in patients with advanced colorectal cancer. Cancer Med. 2014 Aug;3(4):988-97. doi: 10.1002/cam4.263. Epub 2014 Jun 6.
    Results Reference
    result
    Available IPD and Supporting Information:
    Available IPD/Information Type
    CSR Synopsis
    Available IPD/Information URL
    http://www.merck.com/clinical-trials/study.html?id=P04721&kw=P04721&tab=access

    Learn more about this trial

    A Study to Determine the Activity of Robatumumab (SCH 717454, MK-7454) in Participants With Relapsed or Recurrent Colorectal Cancer (P04721, MK-7454-003)

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