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

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00551213
Collaborator
(none)
67
2
18.4

Study Details

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
67 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Nov 21, 2007
Actual Primary Completion Date :
Jun 4, 2009
Actual Study Completion Date :
Jun 4, 2009

Arms and Interventions

Arm Intervention/Treatment
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.

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.

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)

Outcome Measures

Primary Outcome Measures

  1. 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 [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.

Secondary Outcome Measures

  1. Number of Participants Who Experienced One or More Adverse Events (AEs) [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.

  2. Best Overall Tumor Response Per Investigator Review [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.

  3. Number of Participants Who Discontinued Study Drug Due to an AE [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.

  4. Best Overall Tumor Response Per Central Review [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.

  5. Change From Baseline in Tumor Growth Rate [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT00551213
Other Study ID Numbers:
  • P04721
  • MK-7454-003
First Posted:
Oct 30, 2007
Last Update Posted:
Aug 24, 2018
Last Verified:
Jul 1, 2018
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Merck Sharp & Dohme LLC
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Robatumumab→Robatumumab Chemotherapy→Robatumumab
Arm/Group 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.
Period Title: Overall Study
STARTED 50 17
Treated 49 15
COMPLETED 0 0
NOT COMPLETED 50 17

Baseline Characteristics

Arm/Group Title Robatumumab→Robatumumab Chemotherapy→Robatumumab Total
Arm/Group Description Participants receive 1 dose of robatumumab 0.3 mg/kg IV 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. 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. Total of all reporting groups
Overall Participants 50 17 67
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
64.7
(10.8)
61.9
(10.6)
64.0
(10.7)
Sex: Female, Male (Count of Participants)
Female
30
60%
9
52.9%
39
58.2%
Male
20
40%
8
47.1%
28
41.8%

Outcome Measures

1. Primary Outcome
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)

Outcome Measure Data

Analysis Population Description
All participants who received ≥1 dose of robatumumab in Periods 1 and 2 and had SUV data before and after the first dose of robatumumab in Period 2 were included in the analysis. No participants in the Chemotherapy→Robatumumab group received robatumumab in Period 1.
Arm/Group Title Robatumumab→Robatumumab Chemotherapy→Robatumumab
Arm/Group Description Participants receive 1 dose of robatumumab 0.3 mg/kg IV 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. 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.
Measure Participants 41 0
Number [Participants]
7
14%
2. Secondary Outcome
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)

Outcome Measure Data

Analysis Population Description
All participants who received ≥1 dose of study drug were included in the analysis.
Arm/Group Title Robatumumab→Robatumumab Chemotherapy→Robatumumab
Arm/Group Description Participants receive 1 dose of robatumumab 0.3 mg/kg IV 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. 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.
Measure Participants 49 15
Number [Participants]
49
98%
15
88.2%
3. Secondary Outcome
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)

Outcome Measure Data

Analysis Population Description
All participants who received ≥1 dose of robatumumab were included in the analysis.
Arm/Group Title Robatumumab→Robatumumab Chemotherapy→Robatumumab
Arm/Group Description Participants receive 1 dose of robatumumab 0.3 mg/kg IV 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. 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.
Measure Participants 49 15
Partial Response
1
2%
0
0%
Stable Disease
10
20%
7
41.2%
Progressive Disease
33
66%
6
35.3%
No post-Baseline assessment
5
10%
2
11.8%
4. Secondary Outcome
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)

Outcome Measure Data

Analysis Population Description
All participants who received ≥1 dose of study drug were included in the analysis.
Arm/Group Title Robatumumab→Robatumumab Chemotherapy→Robatumumab
Arm/Group Description Participants receive 1 dose of robatumumab 0.3 mg/kg IV 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. 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.
Measure Participants 49 15
Number [Participants]
6
12%
3
17.6%
5. Secondary Outcome
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)

Outcome Measure Data

Analysis Population Description
All participants who received ≥1 dose of robatumumab were included in the analysis.
Arm/Group Title Robatumumab→Robatumumab Chemotherapy→Robatumumab
Arm/Group Description Participants receive 1 dose of robatumumab 0.3 mg/kg IV 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. 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.
Measure Participants 49 15
Partial Response
0
0%
0
0%
Stable Disease
10
20%
5
29.4%
Progressive Disease
31
62%
9
52.9%
No post-Baseline assessment
8
16%
1
5.9%
6. Secondary Outcome
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

Outcome Measure Data

Analysis Population Description
All participants who received ≥1 dose of robatumumab in Periods 1 and 2 were included in the analysis. No participants in the Chemotherapy→Robatumumab group received robatumumab in Period 1.
Arm/Group Title Robatumumab→Robatumumab Chemotherapy→Robatumumab
Arm/Group Description Participants receive 1 dose of robatumumab 0.3 mg/kg IV 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. 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.
Measure Participants 49 0
Pre Baseline 1 (n=46)
0.49
(0.48)
Cycle 1 (n=24)
0.07
(0.67)
Cycle 2 (n=25)
0.41
(0.57)
Cycle 5 (n=25)
0.53
(0.63)
Cycle 9 (n=7)
0.19
(0.26)

Adverse Events

Time Frame Up to approximately 22 weeks
Adverse Event Reporting Description All participants who received ≥1 dose of study drug. Adverse events are reported based on the study drug a participant was taking at the time of the event.
Arm/Group Title Chemotherapy→Robatumumab Robatumumab→Robatumumab
Arm/Group 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. Participants receive 1 dose of robatumumab 0.3 mg/kg IV 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.
All Cause Mortality
Chemotherapy→Robatumumab Robatumumab→Robatumumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN)
Serious Adverse Events
Chemotherapy→Robatumumab Robatumumab→Robatumumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 6/15 (40%) 14/49 (28.6%)
Cardiac disorders
ATRIAL FIBRILLATION 0/15 (0%) 0 1/49 (2%) 1
Gastrointestinal disorders
ABDOMINAL DISTENSION 1/15 (6.7%) 1 0/49 (0%) 0
ABDOMINAL PAIN 0/15 (0%) 0 3/49 (6.1%) 4
CONSTIPATION 0/15 (0%) 0 1/49 (2%) 1
DIARRHOEA 1/15 (6.7%) 1 1/49 (2%) 2
INTESTINAL OBSTRUCTION 0/15 (0%) 0 1/49 (2%) 1
NAUSEA 0/15 (0%) 0 3/49 (6.1%) 4
SMALL INTESTINAL OBSTRUCTION 1/15 (6.7%) 2 0/49 (0%) 0
UPPER GASTROINTESTINAL HAEMORRHAGE 0/15 (0%) 0 1/49 (2%) 1
VOMITING 0/15 (0%) 0 3/49 (6.1%) 4
General disorders
ASTHENIA 0/15 (0%) 0 1/49 (2%) 1
CATHETER RELATED COMPLICATION 0/15 (0%) 0 1/49 (2%) 1
CHEST PAIN 0/15 (0%) 0 1/49 (2%) 1
MALAISE 0/15 (0%) 0 1/49 (2%) 2
PAIN 0/15 (0%) 0 1/49 (2%) 2
CHILLS 1/15 (6.7%) 1 0/49 (0%) 0
PYREXIA 1/15 (6.7%) 2 0/49 (0%) 0
Hepatobiliary disorders
CHOLECYSTITIS ACUTE 0/15 (0%) 0 1/49 (2%) 1
CHOLELITHIASIS 0/15 (0%) 0 1/49 (2%) 1
HEPATIC FUNCTION ABNORMAL 0/15 (0%) 0 1/49 (2%) 1
HYPERBILIRUBINAEMIA 1/15 (6.7%) 2 0/49 (0%) 0
Infections and infestations
BACTERAEMIA 1/15 (6.7%) 1 0/49 (0%) 0
CELLULITIS 0/15 (0%) 0 1/49 (2%) 1
KLEBSIELLA BACTERAEMIA 0/15 (0%) 0 1/49 (2%) 1
PERIHEPATIC ABSCESS 0/15 (0%) 0 1/49 (2%) 1
PNEUMONIA 0/15 (0%) 0 1/49 (2%) 1
SEPSIS 0/15 (0%) 0 1/49 (2%) 1
TOOTH INFECTION 0/15 (0%) 0 1/49 (2%) 1
Metabolism and nutrition disorders
DEHYDRATION 2/15 (13.3%) 2 1/49 (2%) 1
Musculoskeletal and connective tissue disorders
BACK PAIN 0/15 (0%) 0 1/49 (2%) 1
MUSCULOSKELETAL CHEST PAIN 1/15 (6.7%) 1 0/49 (0%) 0
Nervous system disorders
DIZZINESS 0/15 (0%) 0 1/49 (2%) 1
Psychiatric disorders
MENTAL STATUS CHANGES 1/15 (6.7%) 1 0/49 (0%) 0
Renal and urinary disorders
RENAL FAILURE ACUTE 0/15 (0%) 0 1/49 (2%) 1
Respiratory, thoracic and mediastinal disorders
DYSPNOEA 1/15 (6.7%) 1 1/49 (2%) 1
HYPOXIA 0/15 (0%) 0 1/49 (2%) 1
ACUTE RESPIRATORY FAILURE 1/15 (6.7%) 1 0/49 (0%) 0
Vascular disorders
DEEP VEIN THROMBOSIS 0/15 (0%) 0 1/49 (2%) 1
Other (Not Including Serious) Adverse Events
Chemotherapy→Robatumumab Robatumumab→Robatumumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 15/15 (100%) 48/49 (98%)
Blood and lymphatic system disorders
ANAEMIA 1/15 (6.7%) 1 2/49 (4.1%) 11
LEUKOPENIA 1/15 (6.7%) 4 0/49 (0%) 0
LYMPHOPENIA 1/15 (6.7%) 1 1/49 (2%) 1
NEUTROPENIA 1/15 (6.7%) 10 1/49 (2%) 1
Cardiac disorders
SINUS TACHYCARDIA 1/15 (6.7%) 1 0/49 (0%) 0
VENTRICULAR EXTRASYSTOLES 1/15 (6.7%) 1 0/49 (0%) 0
Ear and labyrinth disorders
EAR HAEMORRHAGE 1/15 (6.7%) 1 0/49 (0%) 0
Eye disorders
LACRIMATION INCREASED 1/15 (6.7%) 1 1/49 (2%) 1
MYODESOPSIA 1/15 (6.7%) 1 0/49 (0%) 0
PHOTOPSIA 1/15 (6.7%) 1 0/49 (0%) 0
Gastrointestinal disorders
ABDOMINAL PAIN 5/15 (33.3%) 6 15/49 (30.6%) 23
ABDOMINAL PAIN UPPER 1/15 (6.7%) 1 4/49 (8.2%) 5
ASCITES 1/15 (6.7%) 1 1/49 (2%) 1
CONSTIPATION 6/15 (40%) 7 16/49 (32.7%) 22
DIARRHOEA 8/15 (53.3%) 12 14/49 (28.6%) 19
DRY MOUTH 1/15 (6.7%) 1 5/49 (10.2%) 5
DYSPHAGIA 1/15 (6.7%) 1 1/49 (2%) 1
ERUCTATION 1/15 (6.7%) 1 0/49 (0%) 0
FLATULENCE 1/15 (6.7%) 1 0/49 (0%) 0
FREQUENT BOWEL MOVEMENTS 1/15 (6.7%) 1 0/49 (0%) 0
GASTROINTESTINAL PAIN 1/15 (6.7%) 1 1/49 (2%) 1
GASTROOESOPHAGEAL REFLUX DISEASE 1/15 (6.7%) 1 1/49 (2%) 1
HAEMATOCHEZIA 1/15 (6.7%) 1 1/49 (2%) 1
NAUSEA 9/15 (60%) 12 24/49 (49%) 31
ODYNOPHAGIA 1/15 (6.7%) 1 1/49 (2%) 1
PROCTALGIA 0/15 (0%) 0 3/49 (6.1%) 5
RECTAL HAEMORRHAGE 1/15 (6.7%) 1 2/49 (4.1%) 2
RECTAL TENESMUS 1/15 (6.7%) 1 0/49 (0%) 0
SALIVARY HYPERSECRETION 1/15 (6.7%) 1 0/49 (0%) 0
STOMATITIS 3/15 (20%) 3 2/49 (4.1%) 2
TOOTHACHE 1/15 (6.7%) 1 2/49 (4.1%) 2
VOMITING 7/15 (46.7%) 9 16/49 (32.7%) 20
ABDOMINAL DISTENSION 1/15 (6.7%) 1 0/49 (0%) 0
General disorders
ASTHENIA 5/15 (33.3%) 6 8/49 (16.3%) 10
CATHETER RELATED COMPLICATION 1/15 (6.7%) 1 0/49 (0%) 0
CATHETER SITE RASH 1/15 (6.7%) 1 1/49 (2%) 1
CHILLS 1/15 (6.7%) 1 1/49 (2%) 1
EARLY SATIETY 1/15 (6.7%) 1 2/49 (4.1%) 2
FATIGUE 9/15 (60%) 11 26/49 (53.1%) 36
GAIT DISTURBANCE 2/15 (13.3%) 2 1/49 (2%) 1
GENERAL PHYSICAL HEALTH DETERIORATION 0/15 (0%) 0 3/49 (6.1%) 3
MUCOSAL INFLAMMATION 1/15 (6.7%) 1 4/49 (8.2%) 4
OEDEMA 1/15 (6.7%) 1 0/49 (0%) 0
OEDEMA PERIPHERAL 3/15 (20%) 4 6/49 (12.2%) 8
PAIN 0/15 (0%) 0 3/49 (6.1%) 3
PERFORMANCE STATUS DECREASED 1/15 (6.7%) 1 0/49 (0%) 0
PYREXIA 2/15 (13.3%) 2 0/49 (0%) 0
PITTING OEDEMA 1/15 (6.7%) 1 1/49 (2%) 1
Hepatobiliary disorders
BILE DUCT STENOSIS 1/15 (6.7%) 1 0/49 (0%) 0
JAUNDICE 1/15 (6.7%) 1 1/49 (2%) 3
Infections and infestations
ORAL HERPES 2/15 (13.3%) 2 0/49 (0%) 0
TOOTH ABSCESS 1/15 (6.7%) 1 0/49 (0%) 0
URINARY TRACT INFECTION 2/15 (13.3%) 3 2/49 (4.1%) 2
TINEA INFECTION 1/15 (6.7%) 1 0/49 (0%) 0
Injury, poisoning and procedural complications
CONTUSION 1/15 (6.7%) 1 3/49 (6.1%) 3
INCISIONAL HERNIA 1/15 (6.7%) 1 0/49 (0%) 0
THERMAL BURN 1/15 (6.7%) 1 0/49 (0%) 0
WRIST FRACTURE 1/15 (6.7%) 1 0/49 (0%) 0
Investigations
BLOOD CALCIUM DECREASED 1/15 (6.7%) 1 0/49 (0%) 0
BLOOD CREATININE INCREASED 0/15 (0%) 0 3/49 (6.1%) 4
GAMMA-GLUTAMYLTRANSFERASE INCREASED 0/15 (0%) 0 4/49 (8.2%) 4
HAEMOGLOBIN DECREASED 1/15 (6.7%) 1 1/49 (2%) 1
INTERNATIONAL NORMALISED RATIO INCREASED 1/15 (6.7%) 1 1/49 (2%) 1
WEIGHT DECREASED 4/15 (26.7%) 9 6/49 (12.2%) 10
Metabolism and nutrition disorders
ANOREXIA 8/15 (53.3%) 10 15/49 (30.6%) 18
DECREASED APPETITE 4/15 (26.7%) 4 3/49 (6.1%) 3
DEHYDRATION 4/15 (26.7%) 4 11/49 (22.4%) 14
HYPERGLYCAEMIA 2/15 (13.3%) 7 7/49 (14.3%) 9
HYPOKALAEMIA 2/15 (13.3%) 3 1/49 (2%) 1
HYPOMAGNESAEMIA 1/15 (6.7%) 1 0/49 (0%) 0
Musculoskeletal and connective tissue disorders
ARTHRALGIA 0/15 (0%) 0 4/49 (8.2%) 4
BACK PAIN 2/15 (13.3%) 2 3/49 (6.1%) 3
GROIN PAIN 1/15 (6.7%) 1 0/49 (0%) 0
MUSCLE SPASMS 1/15 (6.7%) 1 5/49 (10.2%) 6
MUSCULAR WEAKNESS 2/15 (13.3%) 2 0/49 (0%) 0
MUSCULOSKELETAL CHEST PAIN 1/15 (6.7%) 1 1/49 (2%) 2
MUSCULOSKELETAL PAIN 3/15 (20%) 3 3/49 (6.1%) 4
MYALGIA 1/15 (6.7%) 1 3/49 (6.1%) 3
PAIN IN EXTREMITY 0/15 (0%) 0 5/49 (10.2%) 7
FLANK PAIN 1/15 (6.7%) 1 1/49 (2%) 1
Nervous system disorders
COGNITIVE DISORDER 0/15 (0%) 0 3/49 (6.1%) 3
DIZZINESS 1/15 (6.7%) 1 4/49 (8.2%) 4
DYSGEUSIA 2/15 (13.3%) 2 3/49 (6.1%) 3
HEADACHE 2/15 (13.3%) 2 9/49 (18.4%) 11
MEMORY IMPAIRMENT 1/15 (6.7%) 1 2/49 (4.1%) 2
NEUROPATHY PERIPHERAL 2/15 (13.3%) 2 4/49 (8.2%) 5
PERIPHERAL SENSORY NEUROPATHY 2/15 (13.3%) 2 3/49 (6.1%) 3
SCIATICA 1/15 (6.7%) 1 0/49 (0%) 0
Psychiatric disorders
ANXIETY 0/15 (0%) 0 6/49 (12.2%) 6
CONFUSIONAL STATE 1/15 (6.7%) 1 4/49 (8.2%) 5
DEPRESSION 0/15 (0%) 0 5/49 (10.2%) 5
DISORIENTATION 1/15 (6.7%) 1 0/49 (0%) 0
INSOMNIA 2/15 (13.3%) 2 6/49 (12.2%) 8
MENTAL STATUS CHANGES 1/15 (6.7%) 1 0/49 (0%) 0
Renal and urinary disorders
HAEMATURIA 1/15 (6.7%) 1 0/49 (0%) 0
MICTURITION URGENCY 1/15 (6.7%) 1 0/49 (0%) 0
NOCTURIA 0/15 (0%) 0 3/49 (6.1%) 3
POLLAKIURIA 1/15 (6.7%) 1 0/49 (0%) 0
RENAL VEIN THROMBOSIS 1/15 (6.7%) 1 0/49 (0%) 0
URETHRAL OBSTRUCTION 1/15 (6.7%) 1 0/49 (0%) 0
Respiratory, thoracic and mediastinal disorders
COUGH 4/15 (26.7%) 4 8/49 (16.3%) 8
DYSPNOEA 6/15 (40%) 6 6/49 (12.2%) 6
EPISTAXIS 2/15 (13.3%) 2 2/49 (4.1%) 2
HAEMOPTYSIS 1/15 (6.7%) 1 0/49 (0%) 0
OROPHARYNGEAL PAIN 2/15 (13.3%) 3 1/49 (2%) 1
PARANASAL SINUS HYPERSECRETION 1/15 (6.7%) 2 0/49 (0%) 0
RHINORRHOEA 1/15 (6.7%) 1 1/49 (2%) 1
SINUS CONGESTION 1/15 (6.7%) 1 1/49 (2%) 1
Skin and subcutaneous tissue disorders
ALOPECIA 4/15 (26.7%) 5 3/49 (6.1%) 3
DERMATITIS ACNEIFORM 1/15 (6.7%) 1 0/49 (0%) 0
DRY SKIN 3/15 (20%) 3 3/49 (6.1%) 3
ERYTHEMA 2/15 (13.3%) 2 0/49 (0%) 0
NAIL DISCOLOURATION 1/15 (6.7%) 1 0/49 (0%) 0
PRURITUS GENERALISED 1/15 (6.7%) 1 0/49 (0%) 0
RASH 4/15 (26.7%) 4 3/49 (6.1%) 3
SKIN DISCOLOURATION 1/15 (6.7%) 1 0/49 (0%) 0
SKIN DISORDER 1/15 (6.7%) 1 1/49 (2%) 2
SKIN LESION 1/15 (6.7%) 1 0/49 (0%) 0
FACIAL WASTING 1/15 (6.7%) 1 0/49 (0%) 0
PRURITUS 1/15 (6.7%) 1 1/49 (2%) 1
Vascular disorders
FLUSHING 1/15 (6.7%) 2 0/49 (0%) 0
HYPERTENSION 1/15 (6.7%) 1 3/49 (6.1%) 3
HYPOTENSION 2/15 (13.3%) 2 1/49 (2%) 1
DEEP VEIN THROMBOSIS 1/15 (6.7%) 1 1/49 (2%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Investigator agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study.

Results Point of Contact

Name/Title Senior Vice President, Global Clinical Development
Organization Merck Sharp & Dohme Corp.
Phone 1-800-672-6372
Email ClinicalTrialsDisclosure@merck.com
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT00551213
Other Study ID Numbers:
  • P04721
  • MK-7454-003
First Posted:
Oct 30, 2007
Last Update Posted:
Aug 24, 2018
Last Verified:
Jul 1, 2018