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Phase I clinical trial of lenalidomide in combination with sorafenib in patients with advanced cancer.

AbstractBACKGROUND:
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.
AuthorsPrasanth 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 A Wolff, Apostolia M Tsimberidou
JournalInvestigational new drugs (Invest New Drugs) Vol. 32 Issue 2 Pg. 279-86 (Apr 2014) ISSN: 1573-0646 [Electronic] United States
PMID23756764 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiogenesis Inhibitors
  • Immunologic Factors
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Niacinamide
  • Thalidomide
  • Sorafenib
  • raf Kinases
  • Lenalidomide
Topics
  • Adult
  • Aged
  • Angiogenesis Inhibitors (administration & dosage, adverse effects)
  • Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
  • Disease-Free Survival
  • Female
  • Humans
  • Immunologic Factors (administration & dosage, adverse effects)
  • Lenalidomide
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms (drug therapy)
  • Niacinamide (administration & dosage, adverse effects, analogs & derivatives)
  • Phenylurea Compounds (administration & dosage, adverse effects)
  • Protein Kinase Inhibitors (administration & dosage, adverse effects)
  • Sorafenib
  • Thalidomide (administration & dosage, adverse effects, analogs & derivatives)
  • Young Adult
  • raf Kinases (antagonists & inhibitors)

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