P-4 trial background information

The Next Generation of Breast Cancer Prevention:
Clinical Trial Background for NSABP P-4
The Study to Evaluate Letrozole and Raloxifene (STELLAR), or NSABP P-4, is a
clinical trial that represents an opportunity to dramatically reduce the toll of breast
cancer. With 175,000 women diagnosed with invasive beast cancer each year – and
40,000 women dying each year from the disease – NSABP P-4 is designed to evaluate the
efficacy of letrozole, a drug that shows the potential to reduce breast cancer incidence by
more than 70%.
This trial is a collaborative effort with the pharmaceutical industry. Both Eli Lilly &
Company and Novartis Pharmaceuticals are providing drug at no cost. Novartis, the
manufacturer of Letrozole, has committed 30 million dollars in support of the trial.
However, this historic opportunity will disappear if the National Cancer Institute (NCI)
continues to delay the release of $54 million in funding which its Executive Committee
approved in January 2007.
NSABP P-4 Review and Approval Process To-Date
Fall 2005:
NSABP submitted the NSABP P-4 study concept to the NCI’s Division of Cancer Prevention. October 2005:
The NCI’s Executive Committee reviewed and approved the NSABP P-4 study proposal. May 2006:
The NCI’s Clinical Trials Operations Committee (CTOC) and a Special Emphasis Panel approved the trial proposal. October 2006:
The NCI’s Division of Cancer Prevention conditionally approved the full NSABP P-4 protocol, pending review by the U.S. FDA. December 2006:
Full competitive renewal of the NSABP Community Clinical Oncology
Program (CCOP) Research Base award (which included the P-4 study) underwent
peer review at the NCI and was awarded a priority score of 131 – the best grant
proposal score in the nearly 50- year history of NSABP. A Special Emphasis
Panel recommended that the NSABP receive approximately $66 million in direct
funding over a five-year period for NSABP P-4, with $12.3 million recommended
for Year 1.
December 2006:

The U.S. FDA provided approval for the NSABP to proceed with the NSABP P-4 trial January 2007:
The NCI’s Executive Committee issued the agency’s final approval to proceed with the trial on the 22nd. The following day, NCI Director Niederhuber placed the study on hold and continues to delay commencement of the trial. March 2007:
Dr. Niederhuber convened an ad hoc expert panel to further discuss the P-4 trial in an unusual, closed-door session. The same month, prior to the ad hoc panel meeting, Dr. Niederhuber indicated in an interview with the Cancer Letter “it is unlikely that the trial would open this year, if at all.” Health Canada provided approval for the NSABP to proceed with the NSABP P-4 trial at sites located throughout Canada. June 2007:
The report of the ad hoc panel will be presented to the NCI National Cancer Advisory Board (NCAB) on June 14th and 15th. Following the NCAB meeting, Dr. Niederhuber will issue his decision.
The National Surgical Adjuvant Breast and Bowel Project’s (NSABP) P-4 Trial
• NSABP P-4 would be the third in a series of trials for breast cancer prevention. o In 1998, NSABP P-1 found that tamoxifen prevented invasive breast o In 2006, NSABP P-2 found that tamoxifen and raloxifene were equivalent in reducing invasive breast cancer among high-risk trial participants, but raloxifene resulted in fewer serious side effects. o Combined, the two trials provided risk assessments to more than one quarter of a million women, with roughly one million more receiving important educational information at our trial sites. • The NSABP P-4 trial will require four years to accrue 12,800 participants at high risk for developing breast cancer and an additional two-to-three years of follow-up prior to analysis of the study data. • The study would help identify the differential benefits and risks of letrozole and raloxifene, two alternative therapies for breast cancer prevention, among high-risk, post-menopausal women to help them make smarter choices in their fight against this disease.
NSABP Heritage of Breast Cancer Treatment and Prevention
• Since 1971, the NSABP has played a vital role in improving and setting the standard for breast cancer treatment and prevention. • Funded by the NCI, the group has conducted large-scale clinical trials at nearly 200 institutions—and 300 satellite centers—throughout the U.S. and four other countries, enrolling more than 110,000 individuals in breast cancer trials to date. • In the 1970s, the NSABP showed that a total mastectomy was as effective in treating breast cancer as a radical mastectomy; the NSABP went on later to prove lumpectomy was an effective alternative to mastectomy. • The NSABP has been successfully conducting breast cancer prevention trials since 1992, advancing the knowledge base and testing new prevention options through its clinical trials. • Because of the prior breast cancer prevention research trials, an estimated 750,000 women are more aware of their personal risks for developing breast cancer and are aware of what options are available to them; this effort has significantly improved the public health of the nation.

Source: http://www.breastcancerprevention.org/P4background.pdf