Abstract
Pharmacodynamic study using FLT PET/CT in advanced solid malignancies treated with a sequential combination of X-82 and docetaxel
Journal of clinical oncology, Vol.33(15_suppl), pp.TPS2601-TPS2601
05/20/2015
DOI: 10.1200/jco.2015.33.15_suppl.tps2601
Abstract
Abstract only
TPS2601
Background: Clinical experience has shown that despite resolution of tumor pain while on vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKI), pain not only returns, but increases during treatment break. We believe this is due to a withdrawal flare i.e. increased tumor proliferation after VEGFR TKI cessation driven by VEGF. We have previously demonstrated this flare using 18-Fluorothymidine (FLT) PET/CT. ( Liu G et.al. Clin Cancer Res 2011;17:7634-44) A sequential approach synchronizing cell-cycle specific chemotherapy with this withdrawal flare may maximize therapeutic index of chemotherapy. Here we propose a novel sequential study using X-82, a VEGFR TKI with docetaxel using FLT PET/CT to measure change in vascular parameters and proliferation. We plan comparing low and high doses of X-82 to explore if low dose is preferable with chemotherapy. Methods: A phase 1 pharmacodynamic study in advanced solid malignancies is planned. Inclusion criteria include at least one lesion amenable to FLT PET/CT, ECOG performance status of ≤ 1 with normal organ and marrow function. 30 patients will be randomized 1:1 to low dose X-82 (200 mg) or high dose X-82 (400 mg) arm. In Cycle 1, X-82 is administered daily on days 2-15. FLT PET/CT (FLT 1) is obtained on day 1, once on day 12-15 (FLT 2) and day 19-21 (FLT 3). Comparison between FLT 1 and 2 will characterize response to X-82 and FLT 2 and 3 will characterize withdrawal flare. In Cycle 2, docetaxel (75 mg/m2) is administered on day 1, followed by X-82 on days 2-15. FLT PET/CT (FLT 4) once on day 12-15 will characterize response to X-82 and docetaxel. Sequential treatment is continued until progression or unacceptable toxicity. Correlative studies include VEGF levels and X-82 pharmacokinetics. Primary objectives are to evaluate safety, tolerability and FLT PET/CT changes with X-82 alone and with docetaxel. Secondary objectives include evaluating objective response rate to the combination. Toxicities will be monitored based on Pocock stopping boundaries with overall type I error of 0.10. At this time, 2 patients are enrolled on study. After establishing safety, we plan dose expansion cohorts in multiple disease sub-types. Clinical trial information: NCT02146222.
Details
- Title: Subtitle
- Pharmacodynamic study using FLT PET/CT in advanced solid malignancies treated with a sequential combination of X-82 and docetaxel
- Creators
- Murtuza M. Rampurwala - University of Wisconsin–MadisonLakeesha Carmichael - University of Wisconsin–MadisonJens C. Eickhoff - University of Wisconsin Carbone Cancer CenterJill Kolesar - University of Wisconsin Carbone Cancer CenterKimberly Binger - University of Wisconsin–MadisonJennifer Heideman - University of Wisconsin Carbone Cancer CenterScott Perlman - University of Wisconsin–MadisonChris Liang - ReprogeneticsRobert Jeraj - University of Wisconsin–MadisonGlenn Liu - University of Wisconsin Carbone Cancer CenterJustine Yang Bruce - University of Wisconsin Carbone Cancer Center
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.33(15_suppl), pp.TPS2601-TPS2601
- Publisher
- AMER SOC CLINICAL ONCOLOGY
- DOI
- 10.1200/jco.2015.33.15_suppl.tps2601
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 05/20/2015
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984696549702771
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