Phase 1
Completed N=20
Phase I Study of Dalotuzumab (MK-0646) in Combination With Cetuximab and Irinotecan in Participants With Colorectal Cancer (MK-0646-016)
Source: ClinicalTrials.gov NCT00925015 ↗Enrolled (actual)
20
Serious AEs
15.0%
Results posted
Aug 2017
Primary outcomePrimary: Number of Dose-limiting Toxicities (DLTs) — 0; 1 DLT
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Dose-limiting Toxicities (DLTs) |
0; 1 | — |
| PRIMARY Number of Participants With an Adverse Event (AE) |
8; 6; 6 | — |
| SECONDARY Number of Participants With Human Anti-Human Antibody (HAHA) |
0; 0; 0 | — |
| SECONDARY Time to Maximum Concentration (Tmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone in or in Combination With Cetuximab / Irinotecan |
5.0; 3.5 | — |
| SECONDARY Concentration at the End of Infusion (Ceoi) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan |
211.2; 267.3 | — |
| SECONDARY Maximum Concentration (Cmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan |
247.6; 311.9 | — |
| SECONDARY Apparent Terminal Half-life (T1/2) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan |
131.4; 141.4 | — |
| SECONDARY Clearance From Plasma (CL) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan |
0.0049; 0.0038 | — |
| SECONDARY Steady-state Volume of Distribution (Vss) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan |
0.0558; 0.0459 | — |
| SECONDARY 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 |
4.56; 5.39 | — |
| SECONDARY 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 |
19.6; 24.5 | — |
| SECONDARY Tmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
7.9; 2.0 | — |
| SECONDARY Cmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
204.0; 236.5 | — |
| SECONDARY T1/2 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
129.4; 131.9 | — |
| SECONDARY CL of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
7.81; 6.82 | — |
| SECONDARY Vss of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
1.45; 1.32 | — |
| SECONDARY AUC0-24 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
4.02; 4.12 | — |
| SECONDARY AUC0-168 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
18.6; 20.1 | — |
| SECONDARY Tmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
1.0; 1.0 | — |
| SECONDARY Cmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
1.21; 1.13 | — |
| SECONDARY T1/2 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
8.95; 9.67 | — |
| SECONDARY CL of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
12.3; 13.1 | — |
| SECONDARY Vss of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
117; 137 | — |
| SECONDARY AUC0-24 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab |
7.19; 6.64 | — |
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Data sourced from ClinicalTrials.gov (NCT00925015). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.