| General information |
| Database: | DB00305 |
| Objective: | This study aimed to assess the efficacy and safety of combination treatment with lenalidomide and cetuximab in KRASmutant metastatic colorectal cancer patients. |
| Authors: | Siena S, et al |
| Title: | Phase II openlabel study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRASmutant metastatic colorectal cancer. |
| Journal: | PLoS One. |
| Year: | 2013 |
| PMID: | 24244261 |
| Trial Design |
| Clinical Trial Id: | NCT01032291 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | KRASmutated metastatic colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | lenalidomide+ cetuximab |
| Study Type: | a phase II multicenter, openlabel trial |
| Key Patients Feature: | patients were eligible to participate in this study if they were diagnosed with metastatic colorectal adenocarcinoma with a confirmed KRAS mutation status. Patients must have progressed on oxaliplatin and irinotecancontaining regimens, with at least one of these regimens containing bevacizumab. ECOG PS score of patients was less than and equal to 1. |
| Biomarker: | Fc¦ÃR genotyping, EGFR copy number, and immunomodulation |
| Biomark Analysis: | No significant difference in OS was observed between the different genotype groups defined by either Fc¦ÃRIIA or IIIA among these 27 subjects (logrank p value >0.05). In contrast, the correlative analysis of EGFR gene copy number status (FISHpositive or FISHnegative) and OS in the 23 subjects who received lenalidomide plus cetuximab combination therapy showed that OS was significantly longer in EGFR FISHpositive than in EGFR FISHnegative subjects (logrank p value = 0.0294) |
| Control Group Info: | lenalidomide alone |
| Treatment Info: | Phase IIa treatment comprised oral lenalidomide (starting dose 25 mg/day) and intravenous cetuximab (400 mg/m(2) followed by weekly 250 mg/m(2)) in 28day cycles. Inphase IIb patients were randomized to either the phase IIa treatment schedule of lenalidomide plus cetuximab combination therapy or lenalidomide 25 mg/day monotherapy. |
| Primary End Point: | the MTD and response rate. |
| Secondary End Point: | to establish the safety, tolerability, and clinical efficacy of the combination. Identifying biomarkers for validation of clinical efficacy and toxicity was an exploratory objective. |
| Patients Number: | 8(phase IIa); 43(phase IIb) |
| Trial Results |
| DLT_MTD: | phase Iia: 1 patient developed a doselimiting toxicity and the maximum tolerated dose of lenalidomide was determined at 25 mg/day. |
| Objective Response Rate: | Best response was stable disease in 9 patients and study enrollment was terminated prematurely due to lack of efficacy in both treatment arms and failure to achieve the planned response objective. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | terminated |
| Median OS A vs. C: | terminated |
| Adverse Event(agent arm): | The majority of adverse events were grade 1 and 2. In bothphases, the adverse events most commonly attributed to any study drugs were fatigue, rash and other skin disorders, diarrhea, nausea, and stomatitis. |
| Conclusions: | The combination of lenalidomide and cetuximab appeared to be well tolerated but did not have clinically meaningful activity in KRASmutant metastatic colorectal cancer patients. |