Track topics on Twitter Track topics that are important to you
Purpose. Dasatinib is an oral tyrosine kinase inhibitor (TKI) of BCR-ABL and SRC family and ixabepilone is an epothilone B analog. Synergistic activity has been reported when combining dasatinib with chemotherapy. This study was conducted to determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) for this combination. Patients and methods. Patients with metastatic solid tumors who progressed on standard therapy received dasatinib orally daily and ixabepilone IV every 3 weeks at escalating doses using 3 + 3 design. An expansion cohort was studied after reaching the MTD. Pharmacokinetic studies were performed. Results. Nineteen patients were enrolled. No DLTs were observed at dose level (DL) 1 (dasatinib 100 mg and ixabepilone 30 mg/m(2)). At DL 2 (dasatinib 100 mg and ixabepilone 40 mg/m(2)), one patient had multiple DLTs. At DL 3 (dasatinib 150 mg and ixabepilone 40 mg/m(2)), the first patient developed grade 3 AE during cycle 2, the second patient had a DLT and a grade 3 AE during cycle 2. The accrual to DL 3 was halted without reaching the maximally administered dose (MAD) and MTDs were determined to be dasatinib 100 mg and ixabepilone 40 mg/m(2) (DL 2). One patient had a partial response and 12 patients stable disease as their best response. Fourteen patients came off study due to toxicities. Conclusion. The combination of dasatinib and ixabepilone showed modest clinical activity with doses 100 mg orally daily and 40 mg/m(2) IV every 3 weeks, respectively. Treatment related toxicities were seen frequently.
Washington Cancer Institute (WCI)/ Medstar Washington Hospital Center (WHC), 110 Irving Street, NW, Washington, DC, 20010, USA, Pia.M.Herbolsheimer@Medstar.net.
This article was published in the following journal.
Name: Investigational new drugs
Dasatinib exhibited activity in preclinical models of sarcoma. The Sarcoma Alliance for Research through Collaboration (SARC) conducted a multicenter, phase 2 trial of dasatinib in patients with advan...
This phase I trial evaluated LY2603618, a selective inhibitor of the DNA damage checkpoint kinase 1, in combination with gemcitabine. Japanese patients with advanced solid tumors were enrolled. All pa...
Pancreatic neuroendocrine tumors versus carcinoid tumors should be examined separately in clinical trials.Progression-free survival is more clinically relevant as the primary endpoint (rather than res...
This study determined the safety, maximum tolerated dose (MTD), pharmacokinetics, and preliminary efficacy of BI 847325, an oral dual MEK and Aurora kinase inhibitor, in patients with refractory solid...
This study had two aims: (a) to test the hypothesis that advanced age is associated with lower levels of tolerability and clinical benefit to experimental Phase I trial agents; (b) to assess the valid...
Patients are being asked to take part in this study because they have been diagnosed with an advanced solid tumor that is not responding to standard treatments. This study will find the hi...
The purpose of this study is to determine the DLT, MTD and recommended Phase II dose of ixabepilone in Japanese patients with solid tumors.
This phase II trial is studying how well ixabepilone works in treating young patients with refractory solid tumors. Drugs used in chemotherapy, such as ixabepilone, work in different ways ...
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: This phase I trial is studying the side effects and best d...
RATIONALE: Drugs used in chemotherapy, such as ixabepilone and ketoconazole, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving ixabepilone with k...
Fractionation of a vaporized sample as a consequence of partition between a mobile gaseous phase and a stationary phase held in a column. Two types are gas-solid chromatography, where the fixed phase is a solid, and gas-liquid, in which the stationary phase is a nonvolatile liquid supported on an inert solid matrix.
Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquefies; the resulting colloid is called a sol.
An extraction method that separates analytes using a solid phase and a liquid phase. It is used for preparative sample cleanup before analysis by CHROMATOGRAPHY and other analytical methods.
Work that is a report of a pre-planned, usually controlled, clinical study of the safety and efficacy of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques after phase II trials. A large enough group of patients is studied and closely monitored by physicians for adverse response to long-term exposure, over a period of about three years in either the United States or a foreign country.
Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (AEROSOLS) and other colloidal systems; water-insoluble drugs may be given as suspensions.
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...