The Ochsner Cancer Institute Clinical Trials Program

THE BIRTH OF THE CCOP PROGRAM

September 2003 marked the 20^th Anniversary of one of the National Cancer Institute's (NCI) most successful clinical trials programs—the Community Clinical Oncology Program (CCOP), and the 20^th birthday of the Ochsner CCOP.

In the 1980s there was a marked change in patterns of medical practice in the United States particularly in the field of oncology. Although once scarce, there were increasing numbers of well-trained medical and radiation oncologists in most US cities. This change in manpower led to a change in basic referral patterns, and almost 80% of all newly diagnosed cancer patients were being treated in the local community. In 1981, Dr. Vincent DeVita, then Director of the NCI, proposed a new scheme to the Association of Community Cancer Centers for the conduct of clinical trials in community based oncology centers. This was prompted by the recognition of the fact that newly diagnosed cancer patients treated in the local community constituted a major resource for the conduct of clinical trials and that the clinical trials mechanism could be used to rapidly transfer new technology to the community. Dr. DeVita envisioned a national network of as many as 100 non-university based institutions of varying configurations which would link themselves to existing clinical research organizations such as the NCI designated Comprehensive Cancer Centers and the National Cooperative Groups. He predicted that these physicians would play an essential role in the recruitment of the thousands of patients required to test new agents for cancer prevention and treatment. He also proposed that involving non-university oncologists in clinical research would improve the quality of cancer care in the United States (the diffusion hypothesis). This program was designated as the Community Clinical Oncology Program (1-3).

The CCOPs were to receive funding directly from the NCI on a competitive basis. They were also to become a mechanism for the rapid transfer of new cancer technologies to community based hospitals and the physician investigators who participated in the program.

On July 16, 1982 the NCI issued the first request for research grant applications (RFA) for the CCOP program. More than 230 letters of intent were received (including one from Ochsner) in response to the CCOP RFA and 190 grant applications were submitted. In September 1983, 62 CCOP grants were awarded. These CCOPs covered a wide geographic area across the United States. The Ochsner CCOP received one of these first awards in 1983 and has been continuously funded as an NCI CCOP since that time.

The practice of medical oncology, perhaps more than any other medical specialty, has been one gigantic clinical research project. The subspecialty of medical oncology evolved from the NCI's clinical trials program initiated in 1955. In 1955, Leukemia Group A was formed (now the Children's Oncology Group), and in 1956 Leukemia Group B was formed (now The Cancer and Leukemia Group B). In the mid 1950s most cases of advanced cancer or leukemia were referred to major centers for treatment and correspondingly, the NCI-sponsored cooperative groups were composed of university medical centers and other major cancer treatment facilities. Other medical centers were largely excluded because of the lack of well-trained community based oncologists.

THE BIRTH OF THE OCHSNER CANCER INSTITUTE AND THE OCHSNER CCOP

In 1982 the Ochsner Cancer Institute (OCI) was formed for the express purpose of obtaining American College of Surgeons' approval for the cancer program, to establish a Tumor Registry, and to coordinate the cancer clinical trials program. The development of the Ochsner Cancer Institute coincided with the development of the National Cancer Institute CCOP Program and developed in parallel with it. Obtaining the CCOP grant enabled the Ochsner Medical Institutions to handle the huge workload associated with establishing a cancer clinical trials program with the potential for success and longevity.

The CCOP initially affiliated with the Southeastern Cancer Study Group and the University of Alabama Comprehensive Cancer Center. In 1984, the Ochsner CCOP affiliated directly with the National Surgical Adjuvant Breast and Bowel Project, in 1986 with the Mayo Clinic – North Central Cancer Treatment Group and the Eastern Cooperative Oncology Group, and in 1990 with the Radiation Therapy Oncology Group. More recently, the Ochsner CCOP has established an affiliation with the Children's Oncology Group.

INSTITUTIONAL COMMITMENT

CCOP institutions must be fully committed to clinical cancer research and to the development and maintenance of the CCOP. The institutions must agree to help absorb extra costs for CCOP travel and data management support. The Ochsner Clinic Foundation, over the years, has been very supportive of the Ochsner CCOP. Local organizations such as the American Cancer Society and the Komen Foundation have also contributed to CCOP support.

PROFESSIONAL COMMITMENT

It is essential to realize that although CCOPs are formed by relationships between institutions – the NCI, community hospitals, research bases – individuals in the institutions make clinical research a success. Simply stated, unless the principal investigator and affiliated investigators are committed to the program, the program will not work. Physician commitment is absolutely critical to success. The principal investigator must be willing to devote at least 20% of his time to the CCOP. Other physician investigators must take the extra time necessary to enter patients into clinical trials. Also, other physicians in the group must be willing to absorb the time lost by the Principal Investigator for participation in CCOP activities. Physician motivation can be enhanced by involving CCOP investigators in all aspects of research base activities. This includes protocol development, committee memberships and chairmanships as well as administrative assignments. Attendance at research base meetings affords the opportunity for Ochsner oncologists to interact with investigators from across the country.

PRIVATE PATIENTS AND RESEARCH PROTOCOLS

Cancer clinical trials offer patients treatment options. The private physician can be assured that by serving as an investigator for clinical trials, he is contributing to cancer research.

Several years ago we evaluated factors that motivate cancer patients to participate in clinical trials (4).

The motivating factors for participation are really the same for private patients as public hospital patients. The reasons for becoming research subjects vary but basically fall into one or more of the following four categories: 1) Hope that the new treatment will control their disease; 2) Altruism that even if the new treatment does not help them, that the knowledge gained will ultimately help others; 3) Trust that the physician would not have recommended an investigational program if he thought it was harmful; and 4) Trapped by a lack of therapeutic alternatives. The latter feeling is noted in patients who have been heavily previously treated when there is often no possibility of treatment alternatives.

Patients are becoming more medically sophisticated particularly with access to the internet. They are becoming much more aware of clinical trials and clinical trials data. Many come to the Ochsner Clinic Foundation seeking the latest in clinical trials. Those patients are very comfortable with the knowledge that oncologists are constantly seeking better modes of treatment and that best treatment has not yet been found. In many instances specific clinical trials are now actively sought by sophisticated, well-informed patients and their families.

The Ochsner CCOP investigators critically evaluate each clinical trial activated to make sure that the scientific question being asked is valid and that patients would not be subjected to undue risk. It is critically important that all clinical trials that are activated pass what has come to be known as the Gertrude Stein test, which is “a difference is only a difference if a makes a difference”(5).

In 1986 the National Cancer Institute added cancer control research to the CCOP program. This CCOP mandate involved prevention, early detection, symptom management and palliative care. In response to this mandate the Ochsner CCOP hired a cancer control coordinator and became actively involved in the Breast Cancer Prevention Trial, the Prostate Cancer Prevention Trial, various smoking cessation studies, and symptom control studies.

The Breast Cancer Prevention Trial has been one of the major successes of the clinical trials effort (6). The results of this landmark prevention trial established the proof of principle that an agent can reduce a person's risk of developing cancer (7).

This study confirmed a 49% reduction in the occurrence of breast cancer in women at high risk who received tamoxifen compared to those receiving placebo. We also participated in two large chemoprevention studies: one for breast cancer prevention (STAR [Study of Tamoxifen and Raloxifene]), and one for prostate cancer prevention (SELECT [Selenium and Vitamin E Cancer Prevention Trial]).

ACCOMPLISHMENTS OF THE OCI AND THE CCOP

Physician investigators of the Ochsner CCOP have placed over 3,000 patients on National Cancer Institute sponsored cancer treatment trials and over 1,200 patients on chemoprevention or other cancer control protocols. In addition the investigators of the Ochsner CCOP have held positions as members of the Board of Directors of the National Surgical Adjuvant Breast Project (NSABP), Executive Committee of the North Central Cancer Treatment Group (NCCTG), Chairman of the Pathology Committee of the NCCTG, Chairman of the Surgery Committee of the NCCTG, Chair of the Clinical Research Nursing Committee of the NSABP, as well as Chair of the Nursing Committee of the NCCTG. This confirms the strong overall participation of CCOP Investigators in clinical trials. In addition, Ochsner CCOP Investigators have been awarded authorship on over 100 peer reviewed papers dealing with cooperative group research, reaffirming our vital role in the overall national clinical trials program.

In 1992 a series of industrial contracts were negotiated to evaluate new agents for the treatment of cancer. The Ochsner Cancer Institute became instrumental in performing the initial research on the new agents including Taxotere, gemcitabine, oxaliplatin, Avastin, Herceptin and others which have now received FDA approval for cancer treatment. The OCI involvement with industry-sponsored research continues.

The Ochsner Cancer Institute is currently in the process of developing a Phase I clinical trials program to continue our commitment to the development of innovative therapies for clinical cancer care.

Overall, participation in the CCOP program over the last twenty plus years has been very rewarding. There have been many improvements in clinical cancer care as a result of this clinical trials program. The CCOP program will continue to contribute heavily to the nation's cancer control effort as well as the evolution of new cancer treatments, so that one day this disease will be able to be fully controlled if not eradicated.