About CTEP's Support for Cancer Clinical Trials: From Idea to Practice-Changing Results

New Agents and Approaches

Agents Under CTEP IND

The NCI Experimental Therapeutics (NEXT) Program selects agents for NCI-sponsored pre-clinical and clinical development. NCI negotiates Collaborative Research and Development Agreements (CRADAs) to develop and evaluate these agents under CTEP IND. 

For some of these agents, NCI may assemble a drug development Project Team to design the scope of NCI’s initial multi-institutional, multi-disciplinary drug development plan for the proposed agent(s). As part of a Project Team, extramural clinical, translational, and basic scientists collaborate with NCI determine which clinical trials will be conducted across the CTEP clinical trials network sites and how translational science objectives should be incorporated. 

After an agent development plan has been approved and collaborative agreements signed, agents under CTEP IND are available for qualified investigators to propose pre-clinical and clinical research studies. In the ETCTN, all trials involve agents under CTEP IND.

Other Agents and Modalities

Many NCTN and PEP-CTN trials involve agents under CTEP IND, but these networks are also able to lead trials under their IND or trials that are IND exempt. Trials that are IND exempt may be studying investigational radiation therapy, surgery, multiple modalities, or changes to the dose or schedule of approved agents.

Clinical Trial Ideas

Clinical trial ideas are submitted to NCI for review through two primary pathways:

• Smaller, earlier phase trials are submitted by the lead organization within the ETCTN, NCTN, PBTC, or PEP-CTN as Letters of Intent (LOIs) and a decision is made by the NCI CTEP Protocol Review Committee (PRC).
• Larger, later phase trials are submitted by the NCTN Group as Concepts and a decision is made by the NCTN Steering Committees. 

Either way, the LOI or Concept is evaluated by reviewers from across NCI.  Depending on the trial design, this may include people with expertise in:  

• The disease area (CTEP's Clinical Investigations Branch)
• The agent (CTEP's Investigational Drug Branch)
• Biostatistics and clinical trial design (DCTD's Biometric Research Program)
• Radiotherapy (DCTD's Radiation Research Program)
• Cancer imaging (DCTD's Cancer Imaging Program)
• Diagnostics and translational research (DCTD's Cancer Diagnosis Program)
• Quality of life research (NCI's Division of Cancer Prevention)

Protocol Development

After an LOI or Concept is approved, the lead organization works on developing the trial protocol and informed consent based on the approved trial designs. The ETCTN has support from CTEP's Central Protocol Writing Service (CPWS) to write these documents.

When the lead organization submits the protocol and consent documents, they are closely reviewed by NCI experts and a full review is conducted by the CTEP Protocol Review Committee. Reviewers are assigned based on the content of the protocol, and can include disease experts, agent experts, radiation oncologists, biostatisticians, regulatory specialists, pharmacists, imaging experts, translational scientists, quality of life reviewers from the NCI Division of Cancer Prevention, and others as needed. 

CTEP communicates with the lead organization and study team throughout protocol revisions until a protocol and consent are finalized. 

If the study is under CTEP IND, then CTEP is the study sponsor and coordinates closely with the FDA for regulatory submissions and the company for drug distribution. 

When the protocol and consent have been approved by all NCI reviewers, the study is sent to the NCI CIRB for review. 

Preparing for the Trial to Open

As the trial gets close to approval, CTEP's Cancer Trials Support Unit (CTSU) works with the lead organization to develop support documents that help sites more easily open the study: 

• National Coverage Analyses help sites evaluate what items in the protocol are billable to insurance.
• EMR templates to help sites implement the protocol in their local electronic medical record systems.

In preparation for the study to activate, or open for enrollment, CTEP contractors work with the lead protocol organization to set up the study in CTEP systems. CTEP's support for network clinical trials includes electronic applications that make it possible for sites to more easily and efficiently do things like:

• Enroll patients
• Report information about how patients are doing
• Order and track trial drugs under CTEP IND
• Report side effects

After a Trial Opens

After the protocol is finalized and the trial opens to enrollment, CTEP oversight and collaboration with the lead organization continues throughout the life of the trial. 

For all trials run by CTEP's networks, CTEP reviews all proposed amendments to the trial, makes updates in CTEP systems as necessary, monitors accrual, or enrollment, to the trial using our slow accrual tracking rules, and ensures compliance with regulations and NIH grant requirements. 

For trials conducted under CTEP IND, CTEP also distributes the IND agent, monitors adverse events, coordinates communication with the company collaborator, submits reports to the FDA, and generally completes all activities required of an IND sponsor. 

Recent Trial Results