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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)

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ClinicalTrials.gov Identifier: NCT00551213
Recruitment Status : Completed
First Posted : October 30, 2007
Results First Posted : December 15, 2015
Last Update Posted : August 24, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE October 29, 2007
First Posted Date  ICMJE October 30, 2007
Results First Submitted Date  ICMJE November 10, 2015
Results First Posted Date  ICMJE December 15, 2015
Last Update Posted Date August 24, 2018
Actual Study Start Date  ICMJE November 21, 2007
Actual Primary Completion Date June 4, 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 22, 2015)
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 [ Time Frame: After the first robatumumab dose in Period 2 (Up to approximately 4 weeks after first robatumumab dose in Period 1) ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 29, 2007)
Response rate by PET. [ Time Frame: Approximately 4 weeks. ]
Change History Complete list of historical versions of study NCT00551213 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2015)
  • Number of Participants Who Experienced One or More Adverse Events (AEs) [ Time Frame: Up to 30 days after last dose of study drug (Up to approximately 22 weeks) ]
    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 [ Time Frame: Up to 30 days after last dose of study drug (Up to approximately 22 weeks) ]
    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 [ Time Frame: Up to last dose of study drug (Up to approximately 18 weeks) ]
    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 [ Time Frame: Up to 30 days after last dose of study drug (Up to approximately 22 weeks) ]
    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 [ Time Frame: Baseline and up to approximately 22 weeks ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2007)
  • Assess Safety and tolerability of SCH 717454. [ Time Frame: Until discontinuation of SCH 717454. ]
  • Tumor response rate, duration of response, and tumor growth rate. [ Time Frame: Until disease progression. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • Biological: Robatumumab
  • Drug: Irinotecan
  • Biological: Cetuximab
  • Drug: Capecitabine
  • Drug: FOLFOX
    Leucovorin calcium (folinic acid)(FOL) + 5-fluorouracil (F)+ oxaliplatin (OX)
  • Drug: CAPEOX/XELOX
    Capecitabine (CAPE) or Xeloda® (XEL) + oxaliplatin (OX)
  • Drug: FOLFIRI
    Leucovorin calcium (folinic acid)(FOL) + 5-fluorouracil (F)+ irinotecan (IRI)
Study Arms  ICMJE
  • Experimental: Robatumumab→Robatumumab
    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.
    Intervention: Biological: Robatumumab
  • Active Comparator: Chemotherapy→Robatumumab
    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.
    Interventions:
    • Biological: Robatumumab
    • Drug: Irinotecan
    • Biological: Cetuximab
    • Drug: Capecitabine
    • Drug: FOLFOX
    • Drug: CAPEOX/XELOX
    • Drug: FOLFIRI
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 1, 2013)
67
Original Estimated Enrollment  ICMJE
 (submitted: October 29, 2007)
59
Actual Study Completion Date  ICMJE June 4, 2009
Actual Primary Completion Date June 4, 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Canada,   United States
 
Administrative Information
NCT Number  ICMJE NCT00551213
Other Study ID Numbers  ICMJE P04721
MK-7454-003 ( Other Identifier: Merck Protocol Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP