NCI supports a large number of clinical trials through its divisions, from first-in-man studies to phase III trials. The DCTD Cancer Therapy Evaluation Program (CTEP), for example, currently oversees more than 800 clinical trials evaluating new treatments for patients with all forms of cancer, and "is the institute's primary vehicle for conducting definitive, practice-changing clinical trials," says DCTD Director Dr. James Doroshow.
The Division of Cancer Prevention (DCP), which supports clinical trials of agents that may help prevent cancer from developing, also manages the extramural Community Clinical Oncology Program (CCOP) - a network that enables patients and physicians to participate in prevention, treatment, and supportive care clinical trials in their local communities. NCI even sponsors clinical trials in foreign countries, such as a phase III HPV vaccine trial in Costa Rica that is testing the ability of virus-like particle vaccines, originally developed by CCR investigators, as a means of preventing cervical cancer.
Indeed, the intramural program is a testing ground for strategies that can improve clinical testing overall. One of the latest is phase 0 trials. Conducted mostly at the NIH Clinical Center and a few select cancer centers, "Phase 0 allows you to answer very important questions rather than relying on the answers that you've received from animals, which don't always predict what happens in humans," says Dr. Doroshow. These trials, therefore, give a good estimate of whether a drug is worth advancing into phase I and phase II trials, which require a much greater supply of investigational agent, more patients, and more clinical resources.
A common measure of action for conventional chemotherapy has been whether or not a drug kills cancer cells and, therefore, shrinks tumors. Using these criteria, however, many of today's targeted agents would appear not to work. And yet the clinical trials show that they do. For this reason, some researchers are beginning to think about progression-free survival as a worthy endpoint for targeted agents. The monoclonal antibody bevacizumab was recently approved for use in breast cancer based on this endpoint.
Scientists are also exploring how new advances in cancer imaging can be used to measure whether a targeted drug is doing what it should. "In the future we will have targeted therapeutic molecules that, with minor modification, can be imaged to show where they go in the tumor, or if they actually reach the tumor," says Dr. Doroshow. This will open new possibilities for accurate and noninvasive assessment and make the clinical trial experience more patient-friendly and effective.