The National Cancer Institute (NCI) continues to move forward with plans for a restructuring of its Clinical Trials Cooperative Group Program even though budget cuts threaten to affect some of its goals.

The federal government sequester, which cuts 5% of the National Institutes of Health's budget, will likely have an impact on the NCI's plan to boost funding for the clinical trials system from $152 million annually to $178 million. “We'll be doing fewer trials than we have done in the past—that's just inevitable,” says Monica Bertagnolli, MD, chief of the division of surgical oncology at Brigham and Women's Hospital in Boston, Massachusetts and chair of one of the new cooperative groups, the Alliance for Clinical Trials in Oncology. “The need for this kind of work is bigger than ever before, and it's a shame we have to contract our study portfolio.”

The clinical trials system reorganization was prompted by a 2010 Institute of Medicine (IOM) report that recommended 12 major changes aimed at more rapidly translating scientific discoveries into successful patient treatments. Since then, the NCI initiated a number of changes to improve the system, including the consolidation of its groups that conduct clinical trials in adult cancer patients from 9 into 4 groups. The pediatric Children's Oncology Group (COG) was consolidated from 4 groups into 1 approximately 10 years ago, and therefore it will not merge with the others. The new system will be known as the National Clinical Trials Network (NCTN).

All the groups have submitted their applications to the NCI, and its Board of Scientific Advisors ultimately will determine how much funding each of the groups will receive. The proposals are expected to be presented to the board and made public before the end of the year, with new funding starting in March 2014, says Jeffrey Abrams, MD, acting director for clinical research in the NCI's division of cancer treatment and diagnosis and associate director of the Cancer Therapy Evaluation Program.

The groups have already publicly announced and started their consolidations. They include the Alliance for Clinical Trials in Oncology, which is a merger of the Cancer and Leukemia Group B, North American Central Cancer Treatment Group, and American College of Surgeons Oncology Group; the ECOG-ACRIN Cancer Research Group, which is a consolidation of the Eastern Cooperative Oncology Group (ECOG) and the American College of Radiology Imaging Network (ACRIN); and SWOG, which did not merge with any other entities and was formerly known as the Southwest Oncology Group.

“Hopefully, we'll be able to fund 1 children's group and up to 4 adult groups, but it will depend on their scores and how much they ask for,” Dr. Abrams says. “The reorganization is pretty complex, and groups had to send in applications for their operations centers, statistical and data management centers, and integrated translational science centers.” The NCI also accepted applications for up to 1 Canadian collaborative clinical trials network, a radiology and imaging core services center, and lead academic participating sites.

Changing Needs

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  2. Changing Needs
  3. Efficiency and Improvement

Under the old system, different cancer centers would be affiliated with one cooperative group. Now, larger academic centers can apply directly to the NCI as lead academic participating sites, enabling them to conduct trials with any one or more of the network groups. “This award is just for the very large centers because they have to have a high number of enrollments per year,” Dr. Abrams says.

In addition to improving efficiency and not duplicating efforts, the new system is designed to address the changing needs of oncology research. In essence, larger groups with greater membership levels are needed to screen multiple patients in order to find participants with specific molecular subtypes and match them with the right drug trials. Furthermore, the groups need to work closely together to develop and run trials, which is easier with fewer groups, he adds.

One example of a new type of trial the revamped system will help support is NCI-MATCH (Molecular Analysis for Therapy Choice), which is still in the planning stages. The study will involve patients with multiple types of advanced cancer who have not responded to standard therapy. Researchers will conduct genome analyses of the patients' tumors to find drugs that match their mutations.

“We will be working with our partners to build a very large pharmacy of drugs—some not yet approved by the FDA [US Food and Drug Administration]—to develop tailored therapies,” Dr. Abrams says, adding that although such trials have been conducted by individual NCI cancer centers, the goal is for this research to occur at a national level and involve community cancer centers.

In addition, the new system will run fewer large phase 3 studies and more phase 2 studies. Investigators hope to glean more information in phase 2 trials in order to reduce the number of phase 3 studies that fail. Increasing the number of randomized phase 2 trials and evaluating their results will help researchers to better determine whether to commit to the larger phase 3 trials. In the past, phase 2 trials could be conducted by a single cancer center fairly quickly with 30 to 40 patients. Now, these trials will require 100 to 200 patients and will need to be conducted by multiple centers to be completed in a timely manner.

The NCI also developed and implemented a new structure for review and prioritization of the entire cancer research portfolio known as the Clinical Trials Advisory Committee (CTAC), which has been in place for approximately a year and that replaced disease-specific steering committees that reviewed and approved trials for each disease.

Efficiency and Improvement

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  2. Changing Needs
  3. Efficiency and Improvement

It is anticipated that the National Clinical Trials Network will run at a rate of approximately 20,000 patient accruals per year, down from a high of approximately 28,000. In February, the American Society of Clinical Oncology (ASCO) and the IOM's National Cancer Policy Forum hosted the second of 2 workshops to follow up on progress since the IOM's report. “A lot of the discussion focused on what we can do to improve the system in a climate of reduced funding,” says Dr. Bertagnolli, who chaired the workshop planning committee. “There were sessions devoted to more interactions with industry partners and sessions discussing how similar research is done in Europe, which doesn't have a formal, publicly funded cancer research mandate.”

One of the groups, ECOG-ACRIN, has already been operational for approximately 1 year. ACRIN, which previously was considered more of a subspecialty that partnered with other groups, is now a full partner with ECOG. Its leaders are now a part of the scientific committees that design and implement trials, and therefore the imaging piece is included from the outset. At the same time, the reconfigured group now has 3 scientific programs that cover a broader range of research: cancer control and outcomes, therapeutic studies, and biomarker sciences. Approximately 100 clinical trials are currently active across these 3 programs.

“We want to perform more trials that incorporate markers that indicate prognosis or predict the likelihood of response by using technologies like imaging, which provide a rapid and innovative approach to finding out whether or not a new agent is working,” says Robert Comis, MD, group cochair of ECOGACRIN.

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We'll be doing fewer trials than we have done in the past—that's just inevitable.

The group's other cochair, Mitchell Schnall, MD, PhD, adds that at the beginning of its collaboration, the group's scientific leadership recognized that a lot of complementary programs and expertise existed between the two. “We started with the science, and then we firmed up the structure that supports the studies,” he says.

One example is a recently approved study to determine which patients with breast cancer diagnosed with ductal carcinoma in situ would benefit from adjuvant therapy alone. It combines a molecular assay along with magnetic resonance imaging of the breast and clinical assessments to help determine low-risk patients. Other studies in patients with various cancers are incorporating new imaging agents in an effort to better identify malignancies.

Still another study is working to determine which patients with melanoma with BRAF genetic mutations respond best to BRAF inhibitors. It combines the use of a new imaging agent with biology from the laboratory as well as immunological and clinical components to better understand patients' responses and the development of resistance to these drugs, Dr. Comis notes.

ECOG-ACRIN investigators also have proposed the Surveillance Trial to Increase Longevity Among Lung Cancer Patients (STILL) to compare established patterns of imaging surveillance with alternative approaches to improve the effectiveness of care and reduce its costs. STILL would study patients with surgically resected lung cancer who are receiving adjuvant chemotherapy and should provide evidence for defining the imaging modality and frequency of surveillance in lung cancer treatment.

Overall, Dr. Abrams says, “We're enthusiastic about the reshaping of this program. We've received a large number of applications, so I'm optimistic this will be a positive first step for our long-standing cooperative groups program.”