Colorectal CancerPhase 1NCT00925015
Phase I Study of Dalotuzumab (MK-0646) in Combination With Cetuximab and Irinotecan in Participants With Colorectal Cancer (MK-0646-016)
A Phase 1 study testing Dalotuzumab 10 mg/kg, Cetuximab and Irinotecan in people with Colorectal Cancer, run by Merck Sharp & Dohme LLC.
Trial summary
The purposes of this study were to assess the safety, tolerability, pharmacokinetic interactions, and the Human Anti-Human Antibody of dalotuzumab in combination with cetuximab and irinotecan in participants with advanced or metastatic colorectal cancer in Japan. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Dalotuzumab 10 mg/kg, Cetuximab and Irinotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- 17 Jun 2009to 6 Dec 2010
- Phase
- Phase 1
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Is 20 years of Age or older
- Has a histologically or cytologically confirmed colorectal cancer
- Has previously failed both Irinotecan and Oxaliplatin containing regimens and should have progressed on or within 3 months of completing their last line of therapy with objective radiological evidence of progression as verified by previous radiologic scans
- Must have adequate organ function
Who cannot join
- Has had chemotherapy, radiotherapy, or biological therapy within 4 weeks prior to initial dosing on this study or whose toxicities from agents administrated 4 weeks earlier have not resolved to at least grade 1 or baseline
- Has experienced intolerable toxicity to Irinotecan therapy
- Has prior exposure to insulin-like growth factor 1 receptor (IGF-1R) inhibitors or epidermal growth factor receptor (EGFR) inhibitors (e.g. Cetuximab)
- Is concurrently using growth hormone (GH), Or GH inhibitors
About this study
Official title: A Phase I Study of MK-0646 in Combination With Cetuximab and Irinotecan in Patients With Advanced or Metastatic Colorectal Cancer
The purposes of this study were to assess the safety, tolerability, pharmacokinetic interactions, and the Human Anti-Human Antibody of dalotuzumab in combination with cetuximab and irinotecan in participants with advanced or metastatic colorectal cancer in Japan.
- Conditions
- Colorectal Cancer
- Being tested
- Dalotuzumab 10 mg/kg, Cetuximab, Irinotecan, Dalotuzumab 15/7.5 mg/kg
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dalotuzumab 10 mg/kgBiological
Also called MK-0646
Dalotuzumab at 10 mg/kg was intravenously administered once weekly
CetuximabBiological
Following pre-treatment with a histamine-receptor antagonist, Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2, followed by subsequent once weekly intravenous infusions of 250 mg/m^2
IrinotecanDrug
Irinotecan was administered with an intravenous infusion of 150 mg/m^2, once every other week for 42 days
Dalotuzumab 15/7.5 mg/kgBiological
Also called MK-0646
Dalotuzumab was intravenously administered, with the first infusion of 15 mg/kg, followed by subsequent infusions of 7.5 mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Cetux/Irin - Dmab 10 mg/kg | Experimental | After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in Cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1, 8, 15, 22, 29 and 36. Each cycle was 6 weeks long. Receives: Biological: Dalotuzumab 10 mg/kg; Biological: Cetuximab; Drug: Irinotecan |
| Cetux/Irin - Dmab 15/7.5 mg/kg | Experimental | After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Days 8, 22 and 36; followed in subsequent cycles by treatment with 7.5 mg/kg on Days 8, 22 and 36. Each cycle was 6 weeks long. Receives: Biological: Cetuximab; Drug: Irinotecan; Biological: Dalotuzumab 15/7.5 mg/kg |
| Dmab 10 mg/kg - Cetux/Irin (DDI) | Experimental | Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For Drug-Drug Interaction (DDI). Each cycle was 6 weeks long. Receives: Biological: Dalotuzumab 10 mg/kg; Biological: Cetuximab; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Dose-limiting Toxicities (DLTs)
To be declared a DLT an adverse experience had a causality related to study therapy. DLTs could be adverse experiences possibly, probably, or definitely related to study therapy by the Investigator, and included the following : Grade 4 neutropenia lasting >= 5 days; Grade 3 or 4 neutropenia with fever >38.5°C; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity, except inadequately treated diarrhea, nausea and vomiting, rash, hyperglycemia, and transient abnormality of electrolytes. Anemia, infusion reactions, hypersensitivity reactions, and adverse experiences not-related to study therapy did not qualify as DLTs.
Measured: Four weeks of Cycle 1 treatment (up to 28 days)
Number of Participants With an Adverse Event (AE)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE.
Measured: Approximately 4 weeks after last drug treatment (up to Day 293)
Secondary outcomes (22)
Number of Participants With Human Anti-Human Antibody (HAHA)
Sera were collected from participants prior to administration of the first dose of study drug, every 6 weeks during the study period, then 4 weeks, 8 weeks and 12 weeks post-treatment. A sandwich format enzyme-linked immunosorbent assay (ELISA) was used to detect the presence of HAHA in serum.
Measured: Up to 12 weeks after the last administration of dalotuzumab (up to 349 days)
Time to Maximum Concentration (Tmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone in or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Tmax of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Measured: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Concentration at the End of Infusion (Ceoi) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Ceoi of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Measured: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Maximum Concentration (Cmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Cmax of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Measured: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Apparent Terminal Half-life (T1/2) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The T1/2 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Measured: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Clearance From Plasma (CL) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The CL of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Measured: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Steady-state Volume of Distribution (Vss) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Vss of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Measured: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Area Under the Concentration-time Curve From 0-24 Hours Post-dose (AUC0-24) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The AUC0-24 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Measured: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8 and 24 h after initiation of dalotuzumab infusion
Area Under the Concentration-time Curve From 0-168 Hours Post-dose (AUC0-168) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The AUC0-168 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Measured: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Tmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Tmax of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Cmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Cmax of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
T1/2 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The T1/2 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
CL of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The CL of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Vss of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Vss of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
AUC0-24 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The AUC0-24 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8 and 24 h after initiation of cetuximab infusion
AUC0-168 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The AUC0-168 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Tmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Tmax of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
Cmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Cmax of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
T1/2 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The T1/2 of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29..
Measured: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
CL of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The CL of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
Vss of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Vss of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
AUC0-24 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The AUC0-24 of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Measured: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8 and 24 h after completion of Irinotecan infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2009 (estimated)
- Study start17 Jun 2009
- Primary completion28 Jul 2010
- Study completion6 Dec 2010
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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 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
- NCT00925015
- Sponsor's protocol ID
- 0646-016
- Other IDs
- 2009_602
- Status last verified
- Jul 2018
- First submitted
- 17 Jun 2009
- Last updated
- 15 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
Doi T, Muro K, Yoshino T, Fuse N, Ura T, Takahari D, Feng HP, Shimamoto T, Noguchi K, Ohtsu A. Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. Cancer Chemother Pharmacol. 2013 Sep;72(3):643-52. doi: 10.1007/s00280-013-2240-8. Epub 2013 Aug 7.
PubMed 23921573
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of MK-0646 in Combination With Cetuximab and Irinotecan in Patients With Advanced or Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00925015
- Acronym / sponsor ID
- 0646-016
- Conditions
- Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 17 Jun 2009 (actual)
- Primary completion
- 28 Jul 2010 (actual)
- Study completion
- 6 Dec 2010 (actual)
- First posted
- 19 Jun 2009 (estimated)
- Results
- Posted 2 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purposes of this study were to assess the safety, tolerability, pharmacokinetic interactions, and the Human Anti-Human Antibody of dalotuzumab in combination with cetuximab and irinotecan in participants with advanced or metastatic colorectal cancer in Japan.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cetux/Irin - Dmab 10 mg/kg | Experimental | Biological: Dalotuzumab 10 mg/kg, Biological: Cetuximab, Drug: IrinotecanAfter treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in Cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1, 8, 15, 22, 29 and 36. Each cycle was 6 weeks long. |
| Cetux/Irin - Dmab 15/7.5 mg/kg | Experimental | Biological: Cetuximab, Drug: Irinotecan, Biological: Dalotuzumab 15/7.5 mg/kgAfter treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Days 8, 22 and 36; followed in subsequent cycles by treatment with 7.5 mg/kg on Days 8, 22 and 36. Each cycle was 6 weeks long. |
| Dmab 10 mg/kg - Cetux/Irin (DDI) | Experimental | Biological: Dalotuzumab 10 mg/kg, Biological: Cetuximab, Drug: IrinotecanDmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For Drug-Drug Interaction (DDI). Each cycle was 6 weeks long. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Is 20 years of Age or older
- Has a histologically or cytologically confirmed colorectal cancer
- Has previously failed both Irinotecan and Oxaliplatin containing regimens and should have progressed on or within 3 months of completing their last line of therapy with objective radiological evidence of progression as verified by previous radiologic scans
- Must have adequate organ function
Key exclusion criteria (4 listed)
- Has had chemotherapy, radiotherapy, or biological therapy within 4 weeks prior to initial dosing on this study or whose toxicities from agents administrated 4 weeks earlier have not resolved to at least grade 1 or baseline
- Has experienced intolerable toxicity to Irinotecan therapy
- Has prior exposure to insulin-like growth factor 1 receptor (IGF-1R) inhibitors or epidermal growth factor receptor (EGFR) inhibitors (e.g. Cetuximab)
- Is concurrently using growth hormone (GH), Or GH inhibitors
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 |
|---|---|---|
| Dalotuzumab 10 mg/kgAlso: MK-0646Dalotuzumab at 10 mg/kg was intravenously administered once weekly | Biological | Cetux/Irin - Dmab 10 mg/kg, Dmab 10 mg/kg - Cetux/Irin (DDI) |
| CetuximabFollowing pre-treatment with a histamine-receptor antagonist, Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 | Biological | Cetux/Irin - Dmab 10 mg/kg, Cetux/Irin - Dmab 15/7.5 mg/kg, Dmab 10 mg/kg - Cetux/Irin (DDI) |
| IrinotecanIrinotecan was administered with an intravenous infusion of 150 mg/m^2, once every other week for 42 days | Drug | Cetux/Irin - Dmab 10 mg/kg, Cetux/Irin - Dmab 15/7.5 mg/kg, Dmab 10 mg/kg - Cetux/Irin (DDI) |
| Dalotuzumab 15/7.5 mg/kgAlso: MK-0646Dalotuzumab was intravenously administered, with the first infusion of 15 mg/kg, followed by subsequent infusions of 7.5 mg/kg | Biological | Cetux/Irin - Dmab 15/7.5 mg/kg |
Primary outcome
Number of Dose-limiting Toxicities (DLTs)
Time frame: Four weeks of Cycle 1 treatment (up to 28 days)
To be declared a DLT an adverse experience had a causality related to study therapy. DLTs could be adverse experiences possibly, probably, or definitely related to study therapy by the Investigator, and included the following : Grade 4 neutropenia lasting >= 5 days; Grade 3 or 4 neutropenia with fever >38.5°C; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity, except inadequately treated diarrhea, nausea and vomiting, rash, hyperglycemia, and transient abnormality of electrolytes. Anemia, infusion reactions, hypersensitivity reactions, and adverse experiences not-related to study therapy did not qualify as DLTs.
Number of Participants With an Adverse Event (AE)
Time frame: Approximately 4 weeks after last drug treatment (up to Day 293)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE.
22 secondary outcomes
Number of Participants With Human Anti-Human Antibody (HAHA)
Time frame: Up to 12 weeks after the last administration of dalotuzumab (up to 349 days)
Time to Maximum Concentration (Tmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone in or in Combination With Cetuximab / Irinotecan
Time frame: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Concentration at the End of Infusion (Ceoi) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Time frame: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Maximum Concentration (Cmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Time frame: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Apparent Terminal Half-life (T1/2) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Time frame: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Clearance From Plasma (CL) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Time frame: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Steady-state Volume of Distribution (Vss) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Time frame: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Area Under the Concentration-time Curve From 0-24 Hours Post-dose (AUC0-24) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Time frame: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8 and 24 h after initiation of dalotuzumab infusion
Area Under the Concentration-time Curve From 0-168 Hours Post-dose (AUC0-168) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Time frame: Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Tmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Cmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
T1/2 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
CL of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Vss of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
AUC0-24 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8 and 24 h after initiation of cetuximab infusion
AUC0-168 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Tmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
Cmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
T1/2 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
CL of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
Vss of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
AUC0-24 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Time frame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8 and 24 h after completion of Irinotecan infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23921573Doi T, Muro K, Yoshino T, Fuse N, Ura T, Takahari D, Feng HP, Shimamoto T, Noguchi K, Ohtsu A. Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. Cancer Chemother Pharmacol. 2013 Sep;72(3):643-52. doi: 10.1007/s00280-013-2240-8. Epub 2013 Aug 7.
- 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 1 study testing Dalotuzumab 10 mg/kg, Cetuximab and Irinotecan 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 4 inclusion and 4 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 15 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 2 Aug 2017). 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 Dose-limiting Toxicities (DLTs) (time frame: Four weeks of Cycle 1 treatment (up to 28 days)). The study lists 2 primary outcomes in all. 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 NCT00925015, 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 15 Aug 2018.