Phase I clinical trial of temozolomide and methoxyamine (TRC-102), an inhibitor of base excision repair, in patients with advanced solid tumors.

Temozolomide (TMZ) generates DNA adducts that are repaired by direct DNA and base excision repair mechanisms. Methoxyamine (MX, TRC-102) potentiates TMZ activity by binding to apurinic and apyrimidinic (AP) sites after removal of N-methyladenine and N-methylguanine, inhibiting site recognition of AP endonuclease. We conducted a phase I trial to determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of intravenous MX when given with oral TMZ.

Phase II study of dasatinib (BMS-354825) in patients with metastatic adenocarcinoma of the pancreas.

Background: Src, EphA2, and platelet-derived growth factor receptors α and β are dysregulated in pancreatic ductal adenocarcinoma (PDAC).

Methods: Dasatinib is an oral multitarget tyrosine kinase inhibitor that targets BCR-ABL, c-Src, c-KIT, platelet-derived growth factor receptor β, and EphA2. We conducted a phase II, single-arm study of dasatinib as first-line therapy in patients with metastatic PDAC.

A Phase I study of the combination of oxaliplatin/docetaxel and vandetanib for the treatment of advanced gastroesophageal cancer.

Introduction: This study aimed to assess the safety and tolerability of the multitargeted tyrosine kinase inhibitor, vandetanib (V), in combination with two chemotherapeutic agents, oxaliplatin (O) and docetaxel (D) in advanced gastroesophageal (GE) cancer.

Methods: This was a Phase I study (NCT00732745) with a standard 3+3 dose escalation design. The primary aim was to determine the optimal dose of the combination of vandetanib and OD chemotherapy.

Phase I trial of pomalidomide given for patients with advanced solid tumors.

Purpose: To determine the safety, the maximal tolerated dose, and to assess for any clinical activity of pomalidomide given to patients with advanced solid tumors.

Patients And Methods: Patients with incurable solid tumors were enrolled. Two different dosing schedules were explored.

Phase I trial of sunitinib and gemcitabine in patients with advanced solid tumors.

Purpose: Combining cytotoxic agents with bevacizumab has yielded significant benefits in a number of solid tumors. Combining small-molecule kinase inhibitors of VEGFR with chemotherapy has yet to demonstrate clinical benefit. The dose, schedule and agents used may be critical to the development of this combinatorial therapy.