It seems straightforward — the more rapidly a clinical trial accrues patients, the faster the trial results can be analyzed and used to benefit patients, physicians, and researchers. But only about 2% of the more than one million adults diagnosed with cancer each year enter clinical trials. To expedite answers to several critical cancer treatment questions, five trials were designated "high priority" by the National Cancer Institute in June 1988, and a general push for faster patient accrual began. Four years and 16 additional "highpriority" trials later, the ongoing trials represent about 10% of all phase III studies, but account for more than 30% of the patients accrued to phase in trials, according to Richard Ungerleider, M.D., chief of NCI's Clinical Investigations Branch.

"The high-priority designation raises awareness of the importance of the study to physicians who are not part of NCI's clinical trials network, as well as to the public," explained Ungerleider. The designation is one way that researchers hope to attract patients who would not ordinarily be referred to NCI-sponsored trials. Each year since 1988, the chairmen of NCI's 13 clinical trials cooperative groups have nominated and directed the selection of a series of trials to receive the special designation. The trials are then listed as "high priority" within PDQ, the computer database of clinical trials, as well as being promoted in other ways. At the next cooperative group chairmen's meeting, a fifth series will be nominated.

Public Health Plus Most high-priority trials are studies of common cancers (colon, rectum, bladder, lymph system). They were chosen based on the potentially large public health benefit of better treatments. Altogether, 21 trials have received high-priority status, and for the most part, the special designation has been effective in increasing awareness about the trials and increasing accrual. Two of the first five trials accrued patients in half the expected time, and later trials are also accruing at up to twice the projected rate (see chart). "We anticipate that a number of the ongoing high-priority trials will close by the end of the year," Ungerleider said. 1308

Dr. D. Lawrence Wickcrham

Educational Video To increase patient understanding of his randomized trial, Natale and colleagues created a protocol-specific, 18minule educational video (sponsored by Bristol-Myers Squibb, Co., New York) that was distributed to all the participating physicians in February and March of this year. "It seems to be an extremely effective format, and while we have only preliminary data, accrual seems to have picked up, too," he said. Like patients with breast and colon cancer, bladder cancer patients seem to harbor micrometastases in the early stages of disease. In the protocol, neoadjuvant therapy (chemotherapy before surgery) is compared with surgical removal of the bladder alone (the current standard therapy). The effects of the neoadjuvant therapy can be assessed via presurgical cystoscopy and during the surgery. "In the end we'll be able to determine how well the cystoscopy identifies patients with a good response to therapy, with an eye toward organ preservation," Natale explained. The National Surgical Adjuvant Breast and Bowel Project has had a record five trials designated as high Journal of the National Cancer Institute

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Trials: Where Are They Now?

Three ongoing high-priority trials are admittedly accruing patients "slowly," explained Ungerleider. "Some trials encompass a difficult medical concept that is hard to explain to patients," he said. "This decreases the likelihood that patients will enroll in the trial. "There is a limit to what increased visibility — like a high-priority designation — will do to increase trial participation," he admitted. "But accrual might be even slower without the designation." The Series I (1988) trial that remains open and is accruing slowly is a bladder cancer adjuvant therapy trial headed by Ronald B. Natale, M.D., at the University of Michigan Medical School.

News News alone. The admittedly diverse therapies within the arms of the study make the randomization process more difficult to explain to patients than in other trials, but the slower than desired accrual rate is not that easy to explain, according to Wickerham.

Challenging Protocol "The protocol is very challenging, and it is a little frustrating that patients are not being enrolled quickly," he said. 'The high-priority designation definitely adds to the credibility and visibility of the trial, which should help." This is cur-

rently the only clinical trial addressing adjuvant therapy issues for this group of breast cancer patients. A prostate cancer study in which medical or surgical castration will be compared to no additional treatment after surgery is the slowest of the Series IV high-priority trials in accruing patients. The study opened in 1988, and only about 40% of the 240 necessary participants have been enrolled. At that rate, it will take about 4 years longer than the original 5-year estimate, said NCI's Ungerleider. — KaraSmigel

NCI-DESIGNATED HIGH-PRIORITY TRIALS Series I—Designated June 1988 INT 0067 INT 0080 NCCTG 864751 NSABP R02 NSABP C03

Comparison of Chemotherapy for Non-Hodgkin's Lymphoma Adjuvant Chemotherapy for Bladder Cancer Adjuvant Chemotherapy and Radiation Therapy for Rectal Cancer Adjuvant Chemotherapy With/Without Radiation for Rectal Cancer Adjuvant Chemotherapy Following Surgery for Colon Cancer

CLOSED ACCRUING SLOWLY CLOSED IN HALF THE TIME PROJECTED EXPECTED TO CLOSE IN 1992 CLOSED IN HALF THE TIME PROJECTED

Series H—Designated June 1989 RTOG 8808 INT 0089 INT 0096 INT 0102 NSABP B18 NSABP B21

Radiation With/Without Chemotherapy in Non-Small Cell Lung Cancer Levamisole in Colon Cancer Small-Cell Lung Cancer Node-Negative Breast Cancer Chemotherapy Before or After Surgery for Breast Cancer Occult Stage I Breast Cancer

CLOSED EXPECTED TO CLOSE IN 1992 EXPECTED TO CLOSE IN 1992 ACCRUING ABOVE PROJECTED EXPECTED TO CLOSE IN 1992 ACCRUING SLOWLY

Series III—Designated June 1990 NCCTG 904751 EST 3489 INT 0114

Levamisole as Adjuvant Treatment for Resectable Colon Cancer Post-Remission Therapies in Adult Myeloid Leukemia Levamisole as Adjuvant Treatment for Rectal Cancer

CLOSED IN RECORD TIME ACCRUING AS PROJECTED EXPECTED TO CLOSE IN 1992

Series IV—Designated June 1991 CALGB 9082 EST 1690 NSABP B24 INT 0116 INT 0115 INT 121 EST 3886

Chemotherapy with Bone Marrow Transplantation for Breast Cancer Alpha-Interferon in Metastatic Melanoma Tamoxifen with Lumpectomy for Noninvasive Breast Cancer Adjuvant Chemoradiotherapy for Resected Gastric Cancer Adjuvant Therapy for Non-Small-Cell Lung Cancer Ajuvant Therapy with/without Bone Marrow Transplant for Breast Cancer Comparison of Hormonal Manipulation or Surgery for Prostate Cancer

Vol. 84, No. 17, September 2, 1992

ACCRUING ABOVE PROJECTED ACCRUING AT TWICE THE PROJECTED RATE ACCRUING AT TWICE THE PROJECTED RATE OPENED LATE 1991 OPENED LATE 1991 OPENED LATE 1991 ACCRUING SLOWLY

NEWS

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priority. The slow-moving NSABP B-21 trial is comparing adjuvant therapies for women with node-negative breast cancers that are 1 cm or smaller. "These women are thought to have a good prognosis, but not all of them are cured by surgery," explained D. Lawrence Wickerham, M.D., deputy director of the NSABP Operations Office. The number of women diagnosed within this stage is increasing due to increasing use of screening tests such as mammography. In the trial, women are treated with lumpectomy and either radiation alone, radiation plus tamoxifen, or tamoxifen

"High-priority" trials: where are they now?

It seems straightforward — the more rapidly a clinical trial accrues patients, the faster the trial results can be analyzed and used to benefit patien...
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