This K24 grant application seeks to renew support for the principal investigator to conduct and to mentor trainees in the conduct of patient-oriented clinical research bridging early phase clinical trials with laboratory correlative studies. Key accomplishments made possible by this grant over the past 5 years include, 1) shifting the sources of my research funding from 100% industry and institutional support in 1998 to 85% NTH and 15% industry in 2003; 2) doubling the research activities of the Phase I Program at Vanderbilt, culminating in the award of a Phase I U01 cooperative agreement from NCI in March, 2003; 3) leading a national Phase II trial correlating biological changes in the EGFR signaling pathway in pre- and post-tumor biopsies with clinical outcome in 115 patients with metastatic colorectal cancer treated with gefitinib; 4) leading the clinical-translational research effort in the Vanderbilt SPORE in Gastrointestinal Cancer P50 grant funded by NCI September, 2002; 5) serving on the faculty of national programs designed to foster the careers of young investigators interested in careers in clinical-translational research including the ASCO/AACR Workshop on Methods in Clinical Cancer Research, the Amgen Fellows Alliance, and the Fellows Educational Session of the ASCO annual meeting; and 6) teaching and mentoring fellows and junior faculty at Vanderbilt who have gone on to careers in patient-oriented clinical research. These achievements attest to both the success of the K24 grant mechanism and to my abilities to apply the support from this grant in a fashion consistent with its intended uses. Although much has been accomplished, there is still much to do. I believe that continued support through this K24 award will be essential in my efforts to, 1) perform integrated laboratory-clinical studies that incorporate new technologies, including pharmacogenetic, pharmacogenomic, rumor genomic, and proteomic characterization as part of early phase clinical evaluation of new anticancer agents; 2) to continue to train young investigators to become translational researchers in early phase drug development; and 3) allow the principal investigator sufficient protected time to continue to expand educational activities related to patient-oriented clinical research.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24CA082301-07
Application #
7127204
Study Section
Subcommittee G - Education (NCI)
Program Officer
Gorelic, Lester S
Project Start
1999-09-01
Project End
2010-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
7
Fiscal Year
2006
Total Cost
$166,015
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Manning, H Charles; Merchant, Nipun B; Foutch, A Coe et al. (2008) Molecular imaging of therapeutic response to epidermal growth factor receptor blockade in colorectal cancer. Clin Cancer Res 14:7413-22
Stover, Daniel G; Lockhart, A Craig; Berlin, Jordan D et al. (2008) Phase I trial of pemetrexed plus oxaliplatin administered every other week in patients with metastatic cancer. Invest New Drugs 26:339-45
Rao, Gautam; Crispens, Marta; Rothenberg, Mace L (2007) Intraperitoneal chemotherapy for ovarian cancer: overview and perspective. J Clin Oncol 25:2867-72
Lockhart, Albert Craig; Cropp, Gillian F; Berlin, Jordan D et al. (2006) Phase I/pilot study of SU5416 (semaxinib) in combination with irinotecan/bolus 5-FU/LV (IFL) in patients with metastatic colorectal cancer. Am J Clin Oncol 29:109-15
Rothenberg, Mace L; LaFleur, Bonnie; Levy, Donna E et al. (2005) Randomized phase II trial of the clinical and biological effects of two dose levels of gefitinib in patients with recurrent colorectal adenocarcinoma. J Clin Oncol 23:9265-74
Lockhart, A Craig; Howard, Martin; Hande, Kenneth R et al. (2004) A phase I dose-escalation and pharmacokinetic study of brostallicin (PNU-166196A), a novel DNA minor groove binder, in adult patients with advanced solid tumors. Clin Cancer Res 10:468-75
Rothenberg, Mace L; Liu, P Y; Braly, Patricia S et al. (2003) Combined intraperitoneal and intravenous chemotherapy for women with optimally debulked ovarian cancer: results from an intergroup phase II trial. J Clin Oncol 21:1313-9
Rothenberg, Mace L; Berlin, Jordan D (2003) Therapeutic strategies for metastatic colorectal cancer: simultaneous, sequential, or specific? J Clin Oncol 21:3716-7
Rothenberg, Mace L; Oza, Amit M; Bigelow, Robert H et al. (2003) Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial. J Clin Oncol 21:2059-69