Investigational Drug Steering Committee
The Investigational Drug Steering Committee (IDSC) was established in 2005 at the recommendation of the NCI's Clinical Trials Working Group to collaborate with the NCI in the design and prioritization of early phase drug development trials carried out within the Experimental Therapeutics Clinical Trials Network (ETCTN) with agents for which NCI’s Cancer Therapy and Evaluation Program (CTEP) holds an Investigational New Drug (IND) application.
The IDSC is comprised of the Principal Investigators of CTEP’s Phase 1 U01 and Phase 2 early drug development grants, which collectively make up the NCI’s Experimental Therapeutics Clinical Trial Network (ETCTN)*. Additional IDSC membership include group representatives from the National Clinical Trial Network (NCTN), subject matter experts in clinical trial design, clinical imaging, radiation therapy, pharmacokinetics/pharmacodynamics, biostatistics, and cancer omics, as well as patient advocacy and Health-Related Quality of Life expertise. View the IDSC member roster.
Ongoing IDSC Activities
The IDSC meets four times per year in order to: 1) conduct strategic discussions and provide clinical and scientific input regarding Drug and Clinical Development Plans (DDPs) prepared by NCI’s Experimental Therapeutics Clinical Trial Network (ETCTN) Drug Development Teams for new experimental anti cancer drugs and selected current drugs within the CTEP portfolio; 2) periodically assess, from a strategic perspective, CTEP-approved LOIs as well as unsolicited LOIs that were rejected to determine if the DDP for an agent should be modified; 3) address specific scientific and/or clinical questions with regard to early stage clinical trials and particular drugs or drug classes; 4) provide input regarding the resolution of investigator appeals of CTEP LOI decisions.
DDPs provide the scientific and clinical rational for a clinical trial(s) targeting certain cancer disease site(s) with an investigational drug(s), the phase(s) of the trial and therapeutic strategy (single agent or combination), patient characteristics for trial enrollment, dose and schedule of the drug(s). DDPs also have a biomarker(s) component that can be essential for patient enrollment, therapeutic efficacy and a better understanding of drug action.
For additional information about NCI’s early phase clinical trials activities, please see CTEP’s Investigational Drug Branch.
Other IDSC Activities
- NCI-IDSC Special Symposium: Using Team Science Approaches for the NCI Experimental Drug Development Program
In January, 2013, in preparation for the redesign of NCI’s Early Experimental Therapeutics Program into the ETCTN, the NCI and IDSC brought together a panel of individuals with insight toward creating and managing highly collaborative scientific teams. Read the meeting report and view presentations given by Lewis Cantley, Ken Turteltaud, L. Michelle Bennett, and Levi Garraway.
- Hyperlipidemia and Hyperglycemia Induced by mTOR Pathway Inhibitors
The IDSC convened an interdisciplinary expert panel to review the pathophysiologies of hyperlipidemia and hyperglycemia induced by mTOR pathway inhibitors. The expert panel summarized the incidence of these toxicities in the current literature, provided recommendations for clinical trial screening and monitoring criteria, and provided management guidance and therapeutic goals for when these toxicities happen. This report enables early recognition of mTOR-induced hyperlipidemia and hyperglycemia, regular monitoring and timely intervention in clinical trials. Read the report: Management of Metabolic Effects Associated With Anticancer Agents Targeting the PI3K-Akt-mTOR Pathway.
- Cardiac Toxicity Associated with Antiangiogenic Cancer Therapy
The IDSC convened an interdisciplinary expert panel to review the cardiac toxicities such as hypertension, left ventricular dysfunction, heart failure, and myocardial ischemia and infarction associated with antiangiogenic therapies. The panel summarized the incidences of these toxicities in the current literature, provided recommendations for clinical trial screening and monitoring criteria, and provided management guidance and therapeutic goals upon occurrence of these toxicities. This report enables early recognition of cardia toxicity, regular monitoring and timely intervention in clinical trials. Read the meeting report.
- Phase 1 Clinical Trial Design
The IDSC convened a Workshop in order to discuss the evolving role of the phase 1 clinical trial beyond the simple determination of dose, schedule, and adverse event profile. A report, generated following that workshop, provides a general overview of the designs, goals, and objectives for studies done for the first time in humans, focusing on traditional and adaptive designs, in addition to designs that limit the number of patients accrued at lower and presumably less effective dose levels. Read the workshop report.
- Phase 2 Clinical Trial Design
Phase 2 trials evaluate the activity and toxicity of a new agent either as monotherapy or in combination with another agent. The IDSC provided guidance on trial designs to demonstrate clinical activity and suggested trials may include secondary objectives exploring toxicity, dose scheduling or biomarkers. Recommendations address choice of primary endpoint, patient selection strategies, and statistical designs. Read the public summary report.
- Novel Designs and Endpoints for Phase 2 Trials
An IDSC meeting was held to address the question of improving efficiency of phase 2 clinical trials. First, the IDSC recommended that alternate phase 2 end points should be studied. Second, depending on the characteristics of the specific trial and study population, historical controls or a randomized design may be more appropriate. Third, rational incorporation of biomarkers into phase II trials was encouraged. Last, novel imaging modalities was noted as critical in evaluating the clinical benefit of new cytostatic agents. Read the report: Novel Designs and End Points for Phase II Clinical Trials.
For more information, contact NCI CCCT Program Director, Steven Reeves, Ph.D. at email@example.com.