ACOSOG Z6041
A Phase II Trial of Chemoradiotherapy and Local Excision for uT2uN0 Rectal Cancer
Phase 2N = 79NCT00114231
- Population
- Adults with clinically staged T2N0 distal rectal adenocarcinoma, tumour under 4 cm and under 40% of the rectal circumference, within 8 cm of the anal verge
- Design
- Multi-institutional (26 American College of Surgeons Oncology Group institutions), open-label, single-arm, non-randomised phase 2 trial in patients with clinical T2N0 distal rectal cancer staged by endorectal ultrasound or endorectal coil MRI (tumour under 4 cm, under 40% of the circumference, within 8 cm of the anal verge). Neoadjuvant capecitabine, oxaliplatin and radiation (45 Gy, then a 9 Gy boost, 54 Gy in total) followed by local excision; because of adverse events during chemoradiotherapy the capecitabine dose was reduced and the boost was reduced to 5.4 Gy (50.4 Gy in total). Primary endpoint: 3-year disease-free survival in all eligible patients (intention-to-treat) and in a per-protocol group.
- Primary endpoint
- DFS
- Arms
- Chemoradiotherapy then local excision (experimental, n = 79): Capecitabine and oxaliplatin with radiation (45 Gy plus a 9 Gy boost, later reduced to 5.4 Gy), followed by local excision
- People
- Garcia-Aguilar J, senior author Bleday R
Show the numbers
| Endpoint | Analysis | Chemoradiotherapy then local excision | Control | Effect |
|---|---|---|---|---|
| DFSIntention-to-treat group named in the abstract: all 79 eligible patients who started neoadjuvant chemoradiotherapyEstimated 3-year disease-free survival (primary endpoint), intention-to-treat group | primarymedian follow-up 56 monthsGarcia-Aguilar 2015 | 88.2% at 3 y (81.3–95.8%) | — | Median follow-up 56 months (IQR 46 to 63) for all patients (the open author manuscript measures it from surgery). The abstract states that the observed 3-year disease-free survival was not as high as anticipated. ClinicalTrials.gov lists an actual enrolment of 90; the paper's analysis population is the 79 eligible patients. |
| DFSPer-protocol group: 72 patients who completed chemoradiotherapy, had ypT0, ypT1 or ypT2 tumours and negative resection marginsEstimated 3-year disease-free survival (primary endpoint), per-protocol group | primarymedian follow-up 56 monthsGarcia-Aguilar 2015 | 86.9% at 3 y (79.3–95.3%) | — | Median follow-up 56 months (IQR 46 to 63) is given in the abstract for all patients. The open author manuscript states that the per-protocol analysis was the basis of the sample size (a 3-year disease-free survival below 80% was considered unacceptably low), that the lower limit of its 95% confidence interval reached that threshold, and that the study therefore did not achieve its goal under the strictly pre-set statistical parameters. |
| Endpoint | Analysis | Chemoradiotherapy then local excision | Control | Effect |
|---|---|---|---|---|
| DFSIntention-to-treat group named in the abstract: all 79 eligible patients who started neoadjuvant chemoradiotherapyEstimated 3-year disease-free survival (primary endpoint), intention-to-treat group | primarymedian follow-up 56 monthsGarcia-Aguilar 2015 | 88.2% at 3 y (81.3–95.8%) | — | Median follow-up 56 months (IQR 46 to 63) for all patients (the open author manuscript measures it from surgery). The abstract states that the observed 3-year disease-free survival was not as high as anticipated. ClinicalTrials.gov lists an actual enrolment of 90; the paper's analysis population is the 79 eligible patients. |
| DFSPer-protocol group: 72 patients who completed chemoradiotherapy, had ypT0, ypT1 or ypT2 tumours and negative resection marginsEstimated 3-year disease-free survival (primary endpoint), per-protocol group | primarymedian follow-up 56 monthsGarcia-Aguilar 2015 | 86.9% at 3 y (79.3–95.3%) | — | Median follow-up 56 months (IQR 46 to 63) is given in the abstract for all patients. The open author manuscript states that the per-protocol analysis was the basis of the sample size (a 3-year disease-free survival below 80% was considered unacceptably low), that the lower limit of its 95% confidence interval reached that threshold, and that the study therefore did not achieve its goal under the strictly pre-set statistical parameters. |
Appears in
Sources
Garcia-Aguilar J, Renfro LA, Chow OS, Shi Q, Carrero XW, Lynn PB, et al. Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial. Lancet Oncol. 2015;16(15):1537-1546.