Colorectal CancerPhase 2NCT00551213
A Study to Determine the Activity of Robatumumab (SCH 717454, MK-7454) in Participants With Relapsed or Recurrent Colorectal Cancer (P04721, MK-7454-003)
A Phase 2 study testing Robatumumab, Irinotecan and Cetuximab in people with Colorectal Cancer, run by Merck Sharp & Dohme LLC.
Trial 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]… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Robatumumab, Irinotecan and Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- No sites listed yet
- Study dates
- 21 Nov 2007to 4 Jun 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
About this study
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
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.
Read the 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.
- Conditions
- Colorectal Cancer
- Being tested
- Robatumumab, Irinotecan, Cetuximab, Capecitabine, FOLFOX
- Keywords
- anti-IGF-1R
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RobatumumabBiological
IrinotecanDrug
CetuximabBiological
CapecitabineDrug
FOLFOXDrug
Leucovorin calcium (folinic acid)(FOL) + 5-fluorouracil (F)+ oxaliplatin (OX)
CAPEOX/XELOXDrug
Capecitabine (CAPE) or Xeloda® (XEL) + oxaliplatin (OX)
FOLFIRIDrug
Leucovorin calcium (folinic acid)(FOL) + 5-fluorouracil (F)+ irinotecan (IRI)
| Study group | Role | What they receive |
|---|---|---|
| Robatumumab→Robatumumab | Experimental | 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. Receives: Biological: Robatumumab |
| Chemotherapy→Robatumumab | Active comparator | 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. Receives: Biological: Robatumumab; Drug: Irinotecan; Biological: Cetuximab; Drug: Capecitabine; Drug: FOLFOX; Drug: CAPEOX/XELOX; Drug: FOLFIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After the first robatumumab dose in Period 2 (Up to approximately 4 weeks after first robatumumab dose in Period 1)
Secondary outcomes (5)
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.
Measured: Up to 30 days after last dose of study drug (Up to approximately 22 weeks)
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.
Measured: Up to 30 days after last dose of study drug (Up to approximately 22 weeks)
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.
Measured: Up to last dose of study drug (Up to approximately 18 weeks)
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.
Measured: Up to 30 days after last dose of study drug (Up to approximately 22 weeks)
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.
Measured: Baseline and up to approximately 22 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2007 (estimated)
- Study start21 Nov 2007
- Primary completion4 Jun 2009
- Study completion4 Jun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00551213
- Sponsor's protocol ID
- P04721
- Other IDs
- MK-7454-003
- Status last verified
- Jul 2018
- First submitted
- 29 Oct 2007
- Last updated
- 24 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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.
PubMed 24905030
Study at a glance
From the registry record, last updated by the sponsor on 24 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00551213
- Acronym / sponsor ID
- P04721
- Conditions
- Colorectal Cancer
- Keywords
- anti-IGF-1R
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 21 Nov 2007 (actual)
- Primary completion
- 4 Jun 2009 (actual)
- Study completion
- 4 Jun 2009 (actual)
- First posted
- 30 Oct 2007 (estimated)
- Results
- Posted 15 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Robatumumab→Robatumumab | Experimental | Biological: RobatumumabParticipants 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. |
| Chemotherapy→Robatumumab | Active comparator | Biological: Robatumumab, Drug: Irinotecan, Biological: Cetuximab, Drug: Capecitabine, Drug: FOLFOX, Drug: CAPEOX/XELOX, Drug: FOLFIRIParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Robatumumab | Biological | Chemotherapy→Robatumumab, Robatumumab→Robatumumab |
| Irinotecan | Drug | Chemotherapy→Robatumumab |
| Cetuximab | Biological | Chemotherapy→Robatumumab |
| Capecitabine | Drug | Chemotherapy→Robatumumab |
| FOLFOXLeucovorin calcium (folinic acid)(FOL) + 5-fluorouracil (F)+ oxaliplatin (OX) | Drug | Chemotherapy→Robatumumab |
| CAPEOX/XELOXCapecitabine (CAPE) or Xeloda® (XEL) + oxaliplatin (OX) | Drug | Chemotherapy→Robatumumab |
| FOLFIRILeucovorin calcium (folinic acid)(FOL) + 5-fluorouracil (F)+ irinotecan (IRI) | Drug | Chemotherapy→Robatumumab |
Primary outcome
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.
5 secondary outcomes
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)
Best Overall Tumor Response Per Investigator Review
Time frame: Up to 30 days after last dose of study drug (Up to approximately 22 weeks)
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)
Best Overall Tumor Response Per Central Review
Time frame: Up to 30 days after last dose of study drug (Up to approximately 22 weeks)
Change From Baseline in Tumor Growth Rate
Time frame: Baseline and up to approximately 22 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24905030Lin 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.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Robatumumab, Irinotecan and Cetuximab in people with Colorectal Cancer, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00551213, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2018.