TY - JOUR
T1 - Phase i clinical trial of lenalidomide in combination with sorafenib in patients with advanced cancer
AU - Ganesan, Prasanth
AU - Piha-Paul, Sarina
AU - Naing, Aung
AU - Falchook, Gerald
AU - Wheler, Jennifer
AU - Fu, Siqing
AU - Hong, David S.
AU - Kurzrock, Razelle
AU - Janku, Filip
AU - Laday, Shell
AU - Bedikian, Agop Y.
AU - Kies, Merrill
AU - Wolff, Robert A.
AU - Tsimberidou, Apostolia M.
N1 - Funding Information:
Funding source This research is supported in part by Celgene (provided free lenalidomide and a research grant to Dr. Tsimberidou).
PY - 2014/4
Y1 - 2014/4
N2 - Background Preclinical data have shown that lenalidomide and sorafenib target endothelial cells, inhibiting growth of ocular melanoma cells in a xenograft model. We conducted a Phase I study of lenalidomide and sorafenib in patients with advanced cancer. Methods During the escalation phase, lenalidomide (days 1-21) and sorafenib (days 1-28) were given orally once daily at the following respective doses: level 1 (10 mg, 200 mg); level 2 (10 mg, 400 mg); level 3 (20 mg, 400 mg); and level 4 (25 mg, 400 mg) (1 cycle = 28 days). A "3 + 3" study design was used. Results Forty-one patients were treated (median age: 50 years). The most common diagnoses were adenoid cystic carcinoma (N = 9), ovarian adenocarcinoma (N = 7), and melanoma (N = 6); 142 cycles (median: 3) were administered. No dose-limiting toxicities were noted. The maximum tested dose (dose level 4) was used in the expansion phase. Grade 3-4 treatment-related toxicities were neutropenia, thrombocytopenia, skin rash, and thromboembolism. Of 38 patients who were evaluable for response, stable disease (SD) was noted in 53 % of patients (SD ≥6 months: 16 %). Tumor types with SD ≥ 6 months were as follows: ocular melanoma, 2/2 (100 %); other melanoma, 1/4 (25 %); adenoid cystic carcinoma, 2/9 (22 %); and ovarian cancer, 1/6 (17 %). The median progression-free survival duration was 3.5 months (95 % CI, 1.9-5.0), and the median overall survival duration was 12.3 months (95 % CI, 10.1-14.5). Conclusions Lenalidomide and sorafenib was well tolerated and associated with disease stabilization for ≥6 months in patients with melanoma, adenoid cystic carcinoma, and ovarian adenocarcinoma.
AB - Background Preclinical data have shown that lenalidomide and sorafenib target endothelial cells, inhibiting growth of ocular melanoma cells in a xenograft model. We conducted a Phase I study of lenalidomide and sorafenib in patients with advanced cancer. Methods During the escalation phase, lenalidomide (days 1-21) and sorafenib (days 1-28) were given orally once daily at the following respective doses: level 1 (10 mg, 200 mg); level 2 (10 mg, 400 mg); level 3 (20 mg, 400 mg); and level 4 (25 mg, 400 mg) (1 cycle = 28 days). A "3 + 3" study design was used. Results Forty-one patients were treated (median age: 50 years). The most common diagnoses were adenoid cystic carcinoma (N = 9), ovarian adenocarcinoma (N = 7), and melanoma (N = 6); 142 cycles (median: 3) were administered. No dose-limiting toxicities were noted. The maximum tested dose (dose level 4) was used in the expansion phase. Grade 3-4 treatment-related toxicities were neutropenia, thrombocytopenia, skin rash, and thromboembolism. Of 38 patients who were evaluable for response, stable disease (SD) was noted in 53 % of patients (SD ≥6 months: 16 %). Tumor types with SD ≥ 6 months were as follows: ocular melanoma, 2/2 (100 %); other melanoma, 1/4 (25 %); adenoid cystic carcinoma, 2/9 (22 %); and ovarian cancer, 1/6 (17 %). The median progression-free survival duration was 3.5 months (95 % CI, 1.9-5.0), and the median overall survival duration was 12.3 months (95 % CI, 10.1-14.5). Conclusions Lenalidomide and sorafenib was well tolerated and associated with disease stabilization for ≥6 months in patients with melanoma, adenoid cystic carcinoma, and ovarian adenocarcinoma.
KW - Advanced cancer
KW - Lenalidomide
KW - Phase I trial
KW - Sorafenib
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U2 - 10.1007/s10637-013-9966-3
DO - 10.1007/s10637-013-9966-3
M3 - Article
C2 - 23756764
AN - SCOPUS:84896395358
SN - 0167-6997
VL - 32
SP - 279
EP - 286
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 2
ER -