Developing an ETCTN Study
The initial concept for an ETCTN clinical trial is either developed by a Drug Development Project Team consisting of Project Team Member Applicants (PTMA) or it begins as an unsolicited Letter of Intent (LOI). The major steps in the review process are outlined in the diagram below. Click on any one of the steps for more information.
A flow diagram detailing the entire ETCTN study development and activation process can be found here.
PTMA Resources
Project Team Membership is an opportunity for DF/HCC investigators to contribute to the drug development plan and design of clinical trials for drugs accepted into the NCI’s Experimental Therapeutics program (NExT). Clinical team members then go on to lead the trials developed by the team.
Investigators who are interested in submitting a PTMA should refer to the DF/HCC ETCTN PTMA guidance document as well as the sample biosketch and letters of support below.
PTMA Requests
DF/HCC investigators are invited to apply, using the Project Team Member Application (PTMA) form, to be a clinical, translational, and/or basic scientist Project Team member. The form is available below for any requests that are currently open.
Current Requests for NCI PTMA SubmissioN | Application DUE DATE |
| December 18, 2023 | |
National Clinical Laboratory Network (NCLN) Resources for ETCTN Studies
To expand support for ETCTN studies, a US laboratory network capable of providing centralized, robust assays was established. The National Clinical Laboratory Network (NCLN) will offer validated assays following harmonized SOPs while implementing uniform assay workflow, instrumentation, and data analysis across network labs. The NCLN will feature a centralized specimen biorepository and the support of centralized data reporting.
To access the NCLN, an investigator can request collaboration with the NCLN in their Letter of Intent (LOI). As part of an LOI review, CTEP might also recommend use of the NCLN. The specific NCLN assays to be performed for a trial will be agreed upon by a consensus process among the trial investigators, the NCLN laboratories, and CTEP. This process will happen in parallel with drug commitment. The use of the NCLN is voluntary. The alternative option of an entirely investigator-driven biomarker plan, through BRC review if necessary, is still completely open.
Utilizing the NCLN, provides such benefits as world-class laboratory collaborators with state-of-the-art platforms. Assays will be performed at the NCI’s expense with no need to identify a funding source. Validated SOPs and workflows, including biorepository support, are already in place.
Before the protocol document can be submitted to CTEP, the investigator must submit a Letter of Intent (LOI). LOIs emanating from the Drug Development Plan created by the Drug Development Project Team are considered solicited LOIs. Unsolicited LOIs are submitted by investigators to examine a novel hypothesis that is supported by pre-clinical data for any CTEP agent. Investigators who are planning to submit an LOI should refer to the DF/HCC ETCTN LOI guidance document as well as the sample and letters of support below.
OEWG Timelines
All ETCTN studies are assigned an OEWG target protocol activation date and an absolute deadline. The target activation date is 210 days from the day CTEP conducts their initial review of the LOI while the absolute deadline is 450 days from the initial LOI review. The OEWG timeline does not stop for any reason during the review and pre-activation steps. Additional information regarding OEWG activities and timelines can be found in the guidance document below.
Biomarker Review
Some clinical trials require approval by the NCI Biomarker Review Committee (BRC). The BRC review generally begins at the LOI stage. Additional information regarding the BRC can be found in the guidance document below.
Within 60 days of CTEP granting LOI approval, the investigator must submit the protocol and model consent for review by CTEP and the NCI Central Institutional Review Board (CIRB).
Site selection and Funding
Phase I studies must be open at DF/HCC and at least two other LAOs. Phase 2 studies must be open to all ETCTN LAOs. The DF/HCC UM1 grant is used to cover the costs associated with participants enrolled at DF/HCC only. When a DF/HCC investigator serves as the Protocol Chair for an ETCTN study, the participating LAOs use their own UM1 grant funds to cover the costs of having their institution participate on the study. For more information, refer to the ETCTN Site Selection and Funding Information Sheet below.
OEWG Timelines
All ETCTN studies are assigned an OEWG target protocol activation date and an absolute deadline. The target activation date is 210 days from the day CTEP conducts their initial review of the LOI while the absolute deadline is 450 days from the initial LOI review. The OEWG timeline does not stop for any reason during the review and pre-activation steps. Additional information regarding OEWG activities and timelines can be found in the guidance document below.
Biomarker Review
Some clinical trials require approval by the NCI Biomarker Review Committee (BRC) prior to activation. Additional information regarding the BRC can be found in the guidance document below.
All new ETCTN trials require protocol activation by CTEP. CTEP defines protocol activation as the date when the first patient is eligible to be enrolled in the trial (i.e., all conditions are satisfied and trial documents are posted on the CTSU members’ website) and is the final milestone under the OEWG Guidelines. Once CTEP activates the protocol, organizations may join the study.