Fast-Forward: a randomised clinical trial testing a 1-week course of curative whole breast radiotherapy against a standard 3-week schedule in terms of local cancer control and late adverse effects in women with early breast cancer

Design: Phase III randomised controlled trial. Setting: Hospital oncology departments. Strategy for Reviewing literature: i) Pubmed database searches using the following criteria: breast cancer, radiotherapy, fractionation, trials ii) Direct communication between international researchers Target population: Women with early breast cancer. Health technologies being assessed: Three different radiotherapy fractionation regimens:- 40Gy in 15 fractions over 3 weeks, 27Gy in 5 fractions over 1 week, 26Gy in 5 fractions over 1 week. Measurement of costs and outcomes: The primary endpoint is local tumour relapse in the irradiated breast (the only clinically relevant measure of radiotherapy effect). Secondary endpoints concentrate on adverse effects measured (as in the recent UK START and FAST trials) using photographic assessments of changes in breast appearance due to radiotherapy, physician assessments of early and late radiotherapy adverse effects, and patient self-assessments of symptoms and quality of life (standard instruments). The primary outcome measure for the health economic evaluation is the cost per quality-adjusted life year (QALY) gained from health resource usage and EQ5D health status. Sample size: 4000 patients, distributed evenly between the 3 randomised schedules, provides 80% power with 1-sided significance of 0.025 (to allow for one-sided hypothesis and multiple testing) to exclude an excess of 1.6% in the 5-year local relapse rate in each of the test schedules compared with control (assuming 2% local relapse rate at 5 years). Since local relapse rates are so low, and no measurable difference in local relapse between the two test schedules is expected, interim analyses will also combine the test schedules for comparison with the control for the primary endpoint. This combined analysis will enable an excess of 1.3% in the 5-year local relapse rate for the 1-week test schedules compared with the control to be detected should it unexpectedly exist. For the photographic, quality of life and health economic sub-studies 2196 patients will provide 80% power to enable a difference of 8% in the 5-year rates of late adverse effects to be detected between the test schedules (assuming 35% rate at 5 years). All estimates allow for 10% loss to follow-up or patients being unevaluable. Project timetables (including recruitment rate): The trial will continue until all patients have had 10 years follow up. The trial comprises three different stages subsequent to ethics approval: Set-up (months 0-6): Research + Development and sponsorship approval obtained. ICR-CTSU staff recruited. Quality Assurance undertaken at centres. Centre agreements signed. Recruitment (months 7-54): All 25 centres open to recruitment by the end of month 27. Recruitment of 4000 patients will be completed by month 54 with each of the 25 radiotherapy centres recruiting an average of 4 patients per month. Monitoring visits to all centres will be undertaken during the first 8 years of the trial. Follow-up (months 55-174): collection of follow up data, interim analysis, data checking, primary analysis and publication of tumour control and 5 year adverse event data at 96 months, and analysis of tumour control and late (10 year) adverse effects at 156 months. Final analysis, report writing and dissemination of results will be undertaken between months 156 and 174.