This application is to evaluate promising new therapies for patients with malignant disease in a clinically efficient, regulatory-compliant, and scientifically rigorous research environment. Phase I clinical studies of new anti-cancer therapies continue to evolve as basic / translational research has broadened the targeted opportunities to treat malignant disease. Building upon a strong foundation in the conduct of phase I studies, we have assembled an interactive research team that uses rationally designed clinical trials that enhances the molecular / pharmacologic assessment of new drug activity. These trials and assessment methods are designed ultimately to impact on the clinical care of patients diagnosed with cancer. The overall objective of these Phase l/ll studies is to determine the appropriate dose and schedule of experimental agents for further evaluation of efficacy in solid tumor /hematologic malignancies and to characterize the acute and chronic toxicities of these anti-cancer therapies.
Our Specific Aims are 1) To conduct Phase I clinical trials of novel anti-cancer agents (alone or in combination) in a timely manner;2) To perform detailed pharmacokinetic studies of these new agents and to correlate these observations with relevant clinical I biologically sound endpoints;3) To implement correlative and pharmacodynamic laboratory evaluations in proof of drug mechanism phase I clinical trials and to explore optimal relationships between parameters of drug exposure and biological effects;and 4) To maintain a clinical trial infrastructure that is current and compliant with regulatory standards that assure quality care to patients enrolled on early phase clinical trials. Over the past 4 years, our UO1 Phase I program has enrolled over 500 patients (131 patients/year average), completed 12 trials, submitted 38 Letters of Intent, have 12 ongoing trials and 4 new trials approved, and have over 80 publications directly related to this Collaborative agreement. Our research group remains flexible to expansion and to explore other targets of interest / trial designs as well as well-positioned to further incorporate novel imaging into our early phase clinical trials. Given our productivity, experience, and expertise in early phase clinical trials, we fully expect to enroll 100 patients / year and to complete 2-3 phase l/ll clinical trials/ year via this cooperative agreement. Scientifically, members of our program will continue active participation in the Investigational Drug Steering Committee (IDSC).
|Pili, Roberto; Quinn, David I; Hammers, Hans J et al. (2017) Immunomodulation by Entinostat in Renal Cell Carcinoma Patients Receiving High-Dose Interleukin 2: A Multicenter, Single-Arm, Phase I/II Trial (NCI-CTEP#7870). Clin Cancer Res 23:7199-7208|
|Knorr, Katherine L B; Finn, Laura E; Smith, B Douglas et al. (2017) Assessment of Drug Sensitivity in Hematopoietic Stem and Progenitor Cells from Acute Myelogenous Leukemia and Myelodysplastic Syndrome Ex Vivo. Stem Cells Transl Med 6:840-850|
|Mehrotra, Shailly; Gopalakrishnan, Mathangi; Gobburu, Jogarao et al. (2017) Exposure-Response of Veliparib to Inform Phase II Trial Design in Refractory or Relapsed Patients with Hematological Malignancies. Clin Cancer Res 23:6421-6429|
|Connolly, Roisin M; Li, Huili; Jankowitz, Rachel C et al. (2017) Combination Epigenetic Therapy in Advanced Breast Cancer with 5-Azacitidine and Entinostat: A Phase II National Cancer Institute/Stand Up to Cancer Study. Clin Cancer Res 23:2691-2701|
|Pili, Roberto; Liu, Glenn; Chintala, Sreenivasulu et al. (2017) Combination of the histone deacetylase inhibitor vorinostat with bevacizumab in patients with clear-cell renal cell carcinoma: a multicentre, single-arm phase I/II clinical trial. Br J Cancer 116:874-883|
|LaCerte, Carl; Ivaturi, Vijay; Gobburu, Joga et al. (2017) Exposure-Response Analysis of Alvocidib (Flavopiridol) Treatment by Bolus or Hybrid Administration in Newly Diagnosed or Relapsed/Refractory Acute Leukemia Patients. Clin Cancer Res 23:3592-3600|
|Webster, Jonathan A; Tibes, Raoul; Morris, Larry et al. (2017) Randomized phase II trial of cytosine arabinoside with and without the CHK1 inhibitor MK-8776 in relapsed and refractory acute myeloid leukemia. Leuk Res 61:108-116|
|Reiss, Kim A; Herman, Joseph M; Armstrong, Deborah et al. (2017) A final report of a phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy (LDFWAR) in patients with advanced solid malignancies and peritoneal carcinomatosis with a dose escalation in ovarian and Gynecol Oncol 144:486-490|
|Pratz, Keith W; Rudek, Michelle A; Gojo, Ivana et al. (2017) A Phase I Study of Topotecan, Carboplatin and the PARP Inhibitor Veliparib in Acute Leukemias, Aggressive Myeloproliferative Neoplasms, and Chronic Myelomonocytic Leukemia. Clin Cancer Res 23:899-907|
|Leung, Doris G; Carrino, John A; Wagner, Kathryn R et al. (2015) Whole-body magnetic resonance imaging evaluation of facioscapulohumeral muscular dystrophy. Muscle Nerve 52:512-20|
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