The purpose of this UM1 Cooperative Agreement is to support participation by a consortium of three National Cancer Institute (NCl)-Designated Cancer Centers in a consolidated, integrated NCI Experimental Therapeutics-Clinical Trials Network (ET-CTN) to conduct early phase experimental therapeutics clinical trials. The Consortium of the City of Hope Comprehensive Cancer Center (COH, the Lead Academic Organization, [LAO]), The University of Southern California (USC)/Norris Comprehensive Cancer Center (USC, Associate Organization [AO]) and the University of California, Davis Cancer Center (UCD, AO) has a 20-year history as a multidisciplinary group conducting early phase experimental therapeutics clinical trials of NCI-Sponsored Investigational New Drugs (INDs) under UOl Cooperative Agreements and NOI Contracts. In addition to working within our own Consortium, we have developed collegial arrangements with other U01 and N01 holders to take advantage of their specific expertise and more efficiently complete clinical trials. Our consortium will contribute to ET-CTN agent-specific trans-network drug development teams from the combined expertise of COH, USC, and UCD in the areas of molecular pharmacology, pharmacokinetics, pharmacodynamics, pharmacogenomics, signal transduction, cell cycle regulation, non-invasive imaging, and bioinformatics to conduct innovative, laboratory-directed early phase developmental and pharmacokinetic studies. These early phase studies will lead not only to the assignment of a recommended, biologically effective Phase II dose, and to an understanding of the spectrum of normal tissue toxicity for specific antineoplastic agents that are directed against novel molecular pathways, but will also provide a mechanistic validation of the effects of the agents on critical tumor cell targets, correlate drug-related alterations of tumr and host biologic markers with clinical outcome, and develop new insights into the therapeutic mechanism of action of the compounds both in the laboratory and the clinic. As such, they will advance the ET-CTN overall goal to define better approaches to the development of novel anticancer agents that capitalize on the ability to characterize tumors molecularly and find appropriate biomarkers to select patients most likely to respond to specific agents.

Public Health Relevance

There is a continual need to develop new drugs to treat patients with cancer. The clinical trials to be conducted by the NCI Experimental Therapeutics Clinical Trials Network will provide the dose, schedule, and early evidence of the therapeutic activity of investigational new anticancer agents. In addition, the multi institutional, multi-disciplinary project teams will explore better approaches to the development of novel anticancer agents that capitalize on molecular characterization of cancers.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project with Complex Structure Cooperative Agreement (UM1)
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Special Emphasis Panel (ZCA1)
Program Officer
Ivy, S Percy
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Beckman Research Institute/City of Hope
United States
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Goncalves, Priscila H; Heilbrun, Lance K; Barrett, Michael T et al. (2017) A phase 2 study of vorinostat in locally advanced, recurrent, or metastatic adenoid cystic carcinoma. Oncotarget 8:32918-32929
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
Dorff, Tanya B; Longmate, Jeff A; Pal, Sumanta K et al. (2017) Bevacizumab alone or in combination with TRC105 for patients with refractory metastatic renal cell cancer. Cancer 123:4566-4573
Mohrbacher, Ann M; Yang, Allen S; Groshen, Susan et al. (2017) Phase I Study of Fenretinide Delivered Intravenously in Patients with Relapsed or Refractory Hematologic Malignancies: A California Cancer Consortium Trial. Clin Cancer Res 23:4550-4555
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
Azad, Nilofer S; El-Khoueiry, Anthony; Yin, Jun et al. (2017) Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/stand up 2 cancer study. Oncotarget 8:35326-35338
Somlo, George; Frankel, Paul H; Arun, Banu K et al. (2017) Efficacy of the PARP Inhibitor Veliparib with Carboplatin or as a Single Agent in Patients with Germline BRCA1- or BRCA2-Associated Metastatic Breast Cancer: California Cancer Consortium Trial NCT01149083. Clin Cancer Res 23:4066-4076
Kirschbaum, Mark H; Frankel, Paul; Synold, Timothy W et al. (2016) A phase I pharmacodynamic study of GTI-2040, an antisense oligonucleotide against ribonuclotide reductase, in acute leukemias: a California Cancer Consortium study. Leuk Lymphoma 57:2307-14
Bates, Susan E; Eisch, Robin; Ling, Alexander et al. (2015) Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data. Br J Haematol 170:96-109
Holleran, Julianne L; Beumer, Jan H; McCormick, David L et al. (2015) Oral and intravenous pharmacokinetics of 5-fluoro-2'-deoxycytidine and THU in cynomolgus monkeys and humans. Cancer Chemother Pharmacol 76:803-11

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