This project, managed the Cancer Therapeutics Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis, (DCTD), National Cancer Institute (NCI), was funded with ARRA stimulus funding under the Accelerating Clinical Trials of Novel Oncologic PathWays (ACTNOW) program. The study supported is: """"""""A Phase I Trial of Escalating Doses of the Anti-IGF-1R Monoclonal Antibody IMCA12 and Standard Dose Sorafenib for Treatment of Advanced Hepatocellular Carcinoma."""""""" Trials funded under this ACTNOW will test novel agents (alone, in combination, and with other standard therapies) that target new pathways by which cancer cells grow, metastasize and develop resistance to current treatments. The trials will receive enhanced resources to enable rapid development and approval of the treatment protocol such that 90 days from notification of the award, the trial will either be open to enrollment or in review at the local institutional review board. This timeline is significantly faster than is typically attained by industry-sponsored early clinical trials, and is about 9 months faster than NCI?s standard approach to trial development. This accelerated timeline is possible due to the resources provided by ARRA. These resources will allow more staff to be hired and devoted to protocol writing and statistical plans, and will increase personnel available for database and case report form development. This set of trials will also be greatly enhanced by the ARRA funding which will permit the use of innovative diagnostic scans, specimen sample collection and assay development and adequate reimbursement for the research costs associated with data management at local sites. Lack of funds for these research costs has traditionally resulted in significant delays in time to study initiation. Avoidance of protracted negotiations with pharmaceutical partners, diagnostic companies, and philanthropic organizations, that have usually been needed to bridge the funding gap unmet by NCI, will permit the trials to be activated more quickly. The purpose of this contract is to conduct Phase 2 and early clinical trials of NCI-sponsored agents, evaluate biologic effects of these agents on their molecular targets, evaluate other relevant biologic effects and determine clinically relevant outcomes/correlates. Major emphasis is on Phase 2 studies, pilot protocols that explore promising combination therapies, and high priority studies that are pivotal for drug development and require rapid initiation, completion, and data reporting. NCI staff notify the Contractor of high priority studies as they are identified. NCI also considers investigator-initiated trials for credit under this contract based on available resources and priorities. The contractor will: o Rapidly conduct clinical trials necessary to assess the anti-tumor activity and carry out the development plans for NCI-sponsored agents of varying classes, many of which are directed at new cancer targets. While the majority of trials will be Phase II, some studies designed to develop or assess dose, schedule and pharmacodynamic questions shall be conducted under this contract. o Obtain and process blood, normal and tumor tissue from patients and carry out imaging evaluations for research purposes when required by the protocols. o Study relevant biologics effects of new agents. o Study relevant pharmacology. o Determine the antitumor activity of selected combinations of antitumor agents or combinations involving radiotherapy;and, o Determine the safety and efficacy of these agents and explore pharmacokinetic/pharmacodynamic correlations in special patient populations, such as those with impaired end-organ function, geriatric populations, under-represented racial and/or ethnic groups in whom differences would be anticipated.
