This is a Phase I study of the farnesyltransferase inhibitor, L-778,123 with radiotherapy in patients with lung cancer, head and neck cancer, and pancreatic cancer. Hypothesis is the administration of L-778, 123 for two two week periods in combination with standard radiotherapy at a dose that achieves steady state plasma concentrations of at least 2.0 uM will be generally safe and well tolerated in patients with locally advanced malignancies. The objectives of the study are: Primary: (1) Evaluate the safety and tolerability of L-778,123 including determination of the maximally tolerated dose (MTD), when administered for weeks 1, 2, 4, and 5 of radiotherapy for pancreatic cancer. (2) Define the Recommended Phase II Dose (RPTD) when L-778,123 is administered for Weeks 1 to 5 of radiotherapy for pancreatic cancer. Secondary: (1) Evaluate the safety and tolerability of L-778,123 including determination of the maximally tolerated dose (MTD), when administered for weeks 1, 2, 4, and 5 of radiotherapy for head and neck or non-small cell lung cancer. (2) Define the Recommended Phase II Dose (RPTD) when L-778,123 is administered for Weeks 1 to 5 of radiotherapy for head and neck or non-small lung cancer. (3) Evaluate radiologic or tumor marker responses to treatment with L-778,123. (4) Evaluate the relationship between ras mutations and response to treatment with L-778,123. (5) Evaluate the relationship between plasma drug levels and farnesylation assay results.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000040-40
Application #
6414405
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
1974-10-01
Project End
2002-11-30
Budget Start
Budget End
Support Year
40
Fiscal Year
2000
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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