Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer.
This study aimed to assess the efficacy and safety of combination treatment with lenalidomide and cetuximab in KRAS-mutant metastatic colorectal cancer patients. This was a phase II multicenter, open-label trial comprising a safety lead-in phase (phase IIa) to determine the maximum tolerated dose, a...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3823943?pdf=render |
| _version_ | 1828345091463315456 |
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| author | Salvatore Siena Eric Van Cutsem Mingyu Li Ulf Jungnelius Alfredo Romano Robert Beck Katia Bencardino Maria Elena Elez Hans Prenen Mireia Sanchis Andrea Sartore-Bianchi Sabine Tejpar Anita Gandhi Tao Shi Josep Tabernero |
| author_facet | Salvatore Siena Eric Van Cutsem Mingyu Li Ulf Jungnelius Alfredo Romano Robert Beck Katia Bencardino Maria Elena Elez Hans Prenen Mireia Sanchis Andrea Sartore-Bianchi Sabine Tejpar Anita Gandhi Tao Shi Josep Tabernero |
| author_sort | Salvatore Siena |
| collection | DOAJ |
| description | This study aimed to assess the efficacy and safety of combination treatment with lenalidomide and cetuximab in KRAS-mutant metastatic colorectal cancer patients. This was a phase II multicenter, open-label trial comprising a safety lead-in phase (phase IIa) to determine the maximum tolerated dose, and a randomized proof of concept phase (phase IIb) to determine the response rate of lenalidomide plus cetuximab combination therapy. 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 28-day cycles. In phase IIb patients were randomized to either the phase IIa treatment schedule of lenalidomide plus cetuximab combination therapy or lenalidomide 25 mg/day monotherapy. Eight patients were enrolled into phase IIa. One patient developed a dose-limiting toxicity and the maximum tolerated dose of lenalidomide was determined at 25 mg/day. Forty-three patients were enrolled into phase IIb proof of concept. 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. The majority of adverse events were grade 1 and 2. In both phases, the adverse events most commonly attributed to any study drugs were fatigue, rash and other skin disorders, diarrhea, nausea, and stomatitis. Thirty-nine deaths occurred; none was related to study drug. The combination of lenalidomide and cetuximab appeared to be well tolerated but did not have clinically meaningful activity in KRAS-mutant metastatic colorectal cancer patients.Clinicaltrials.gov NCT01032291. |
| first_indexed | 2024-04-14T00:06:36Z |
| format | Article |
| id | doaj.art-4a568ab78f1f4a15bc80d84a97ec5af2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T00:06:36Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4a568ab78f1f4a15bc80d84a97ec5af22022-12-22T02:23:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01811e6226410.1371/journal.pone.0062264Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer.Salvatore SienaEric Van CutsemMingyu LiUlf JungneliusAlfredo RomanoRobert BeckKatia BencardinoMaria Elena ElezHans PrenenMireia SanchisAndrea Sartore-BianchiSabine TejparAnita GandhiTao ShiJosep TaberneroThis study aimed to assess the efficacy and safety of combination treatment with lenalidomide and cetuximab in KRAS-mutant metastatic colorectal cancer patients. This was a phase II multicenter, open-label trial comprising a safety lead-in phase (phase IIa) to determine the maximum tolerated dose, and a randomized proof of concept phase (phase IIb) to determine the response rate of lenalidomide plus cetuximab combination therapy. 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 28-day cycles. In phase IIb patients were randomized to either the phase IIa treatment schedule of lenalidomide plus cetuximab combination therapy or lenalidomide 25 mg/day monotherapy. Eight patients were enrolled into phase IIa. One patient developed a dose-limiting toxicity and the maximum tolerated dose of lenalidomide was determined at 25 mg/day. Forty-three patients were enrolled into phase IIb proof of concept. 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. The majority of adverse events were grade 1 and 2. In both phases, the adverse events most commonly attributed to any study drugs were fatigue, rash and other skin disorders, diarrhea, nausea, and stomatitis. Thirty-nine deaths occurred; none was related to study drug. The combination of lenalidomide and cetuximab appeared to be well tolerated but did not have clinically meaningful activity in KRAS-mutant metastatic colorectal cancer patients.Clinicaltrials.gov NCT01032291.http://europepmc.org/articles/PMC3823943?pdf=render |
| spellingShingle | Salvatore Siena Eric Van Cutsem Mingyu Li Ulf Jungnelius Alfredo Romano Robert Beck Katia Bencardino Maria Elena Elez Hans Prenen Mireia Sanchis Andrea Sartore-Bianchi Sabine Tejpar Anita Gandhi Tao Shi Josep Tabernero Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer. PLoS ONE |
| title | Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer. |
| title_full | Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer. |
| title_fullStr | Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer. |
| title_full_unstemmed | Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer. |
| title_short | Phase II open-label study to assess efficacy and safety of lenalidomide in combination with cetuximab in KRAS-mutant metastatic colorectal cancer. |
| title_sort | phase ii open label study to assess efficacy and safety of lenalidomide in combination with cetuximab in kras mutant metastatic colorectal cancer |
| url | http://europepmc.org/articles/PMC3823943?pdf=render |
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