Abstract 1178: Phase I clinical trial of Lenalidomide in combination with Sorafenib in patients with advanced cancer.
Authors: Ganesan Prasanth , Piha-Paul Sarina , Naing Aung , Falchook Gerald , Wheler Jennifer , Fu Siqing , Hong David S. , Kurzrock Razelle , Janku Filip , Laday Shell , Bedikian Agop Y. , Kies Merrill , Wolff Robert , Tsimberidou Apostolia M. 
Published: August 2014

Abstract
Background: Preclinical data have shown that lenalidomide and sorafenib target endothelial cells, inhibiting growth of ocular melanoma cells and growth of tumors in a xenograft model (additive to synergistic activity)(Mangiameli et al, J Transl Med 2007;5:38).
Patients and Methods: We conducted a phase 1 study in patients with advanced cancer. During the escalation phase (“3+3” design), lenalidomide (D1-21) and sorafenib (D1-28) were given orally at the following respective daily doses: Level 1 (10mg, 200mg); Level 2 (10mg, 400mg); Level 3 (20mg, 400mg); and Level 4 (25mg, 400mg) (1 cycle=28 days).
Results: Forty-one patients were treated [median age: 50 yrs (16-72); men: 18 (44%); median no. of prior therapies: 3 (0-12); ≥2 metastatic sites: 80%]. The most common diagnoses were adenoid cystic carcinoma (N=9), ovarian adenocarcinoma (N=7) and melanoma (N=6). Overall, 140 cycles (median: 3; range, 1-17) were administered. No DLTs were noted during the escalation phase (N=19) and Level 4 (lenalidomide 25 mg/day D1-21 and sorafenib 400mg/day Day 1-28), the maximum tested dose was used in the expansion phase (N=22). Grade 3-4 treatment-related toxicities were as follows: neutropenia (N=7; 17%), thrombocytopenia (N=2; 5%), skin rash (N=2; 5%) and thromboembolism (N=2; 5%). Thirty-eight patients were evaluable for response. Stable disease (SD) was noted in 20 (53%) patients, including SD ≥6 months in 6 (16%). SD≥6 months by tumor type was as follows: ocular melanoma, 1/1 (100%); other melanoma, 2/5 (40%); adenoid cystic carcinoma, 2/9 (22%); and ovarian cancer, 1/5 (20%) (Table). The median progression-free survival (N=41) was 3.7 months (95% CI, 2.0-5.4) and median overall survival (N=41) was 12.3 months (95% CI, 10.1-14.5).
Conclusions: Lenalidomide 25mg (D1-21) combined with sorafenib 400 mg (D1-28) was well tolerated and it was associated with disease stabilization for ≥6 months in selected patients with melanoma, adenoid cystic carcinoma and ovarian adenocarcinoma.
Characteristics of patients with SD≥6 months Dose level Age/Sex/ECOG PS Diagnosis No. of metastatic sites/no.prior Rx Best RECIST Response,% No. of cycles Reason of treatment discontinuation Survival Status Progression-free survival, months Overall survival, months 3 74/M/2 Adenoid cystic carcinoma 2/1 −17 17 Travel issues Alive 19 19.5 4 55/F/2 Ovarian Cancer 2/10 −5 7 Progr.dis Alive 8 12.1 4 67/F/1 Ocular Melanoma 1/1 −6 7 Ipilimumab became available Alive 8 9.2 4 35/F/1 Melanoma 4/5 −4 14+ On study Alive 13+ 13 4 35/F/0 Adenoid cystic carcinoma 4/1 −1 6 Progr.dis Alive 8 10.5 4 65/M/1 Melanoma 2/1 −8 7 Progr.dis Alive 6 7.4
Citation Format: Prasanth Ganesan, Sarina Piha-Paul, Aung Naing, Gerald Falchook, Jennifer Wheler, Siqing Fu, David S. Hong, Razelle Kurzrock, Filip Janku, Shell Laday, Agop Y. Bedikian, Merrill Kies, Robert Wolff, Apostolia M. Tsimberidou. Phase I clinical trial of Lenalidomide in combination with Sorafenib in patients with advanced cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1178. doi:10.1158/1538-7445.AM2013-1178
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.