Phase I Study of Pemetrexed and Sorafenib in Advanced Malignancy
I. To determine doses for the combination of pemetrexed (pemetrexed disodium) with sorafenib
(sorafenib tosylate) appropriate for Phase II study.
II. To gain additional safety and dosing experience with the combination of pemetrexed and
sorafenib at the recommended phase II dose (RP2D) (s) in a breast cancer expansion cohort.
I. To evaluate the safety, tolerance, and toxicity of the combination of pemetrexed and
II. To observe antitumor effects of the combination. III. To assess the feasibility of
analyzing tissue staining of Beclin1 in biopsy specimens.
IV. To assess the feasibility of analyzing PDGFRb expression in biopsy specimens.
V. To assess the feasibility of analyzing pTEN expression in biopsy specimens. VI. To assess
the feasibility of analyzing ZMP levels (marker of AICART inhibition) in peripheral blood
mononuclear cells (PBMCs), collected before and after pemetrexed administration.
VII. To assess the feasibility of analyzing ZMP levels in circulating tumor cells (CTCs),
collected before and after pemetrexed administration.
VIII. To assess the feasibility of analyzing LC3A levels by immunohistochemistry (IHC) in
CTCs of patients, before and after pemetrexed administration.
OUTLINE: This is a dose-escalation study of pemetrexed disodium and sorafenib tosylate.
Patients receive pemetrexed disodium intravenously (IV) on day 1 every 2 weeks and sorafenib
tosylate orally (PO) twice daily (BID) for 4 weeks. Courses repeat every 4 weeks in the
absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase 2 doses for the combination of pemetrexed disodium with sorafenib tosylate
Maximum doses of pemetrexed and sorafenib, which, when administered in combination are determined to be tolerable and will be tested in a Phase 2 trial for efficacy.
Massey Cancer Center
United States: Institutional Review Board
|Virginia Commonwealth University/Massey Cancer Center||Richmond, Virginia 23298|