X-ACT
XELODA Adjuvant Colon Cancer Trial (X-ACT): capecitabine versus bolus fluorouracil plus leucovorin as adjuvant treatment for stage III colon cancer
Phase 3N = 1,987NCT00009737
- Population
- 1987 patients with resected stage III colon cancer; the intent-to-treat population received capecitabine (1004) or 5-FU/folinic acid (983). The FDA letter describes the approved indication as Dukes' C colon cancer.
- Design
- Multicentre randomised trial of 24 weeks of oral capecitabine (1250 mg/m2 twice daily on days 1-14 every 3 weeks) versus bolus fluorouracil plus leucovorin (Mayo Clinic regimen). Primary efficacy endpoint at least equivalence in disease-free survival (non-inferiority margin for the hazard ratio 1.20); primary safety endpoint the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines. The EMA procedural-steps table refers to the trial as study M66001 (X-ACT). ClinicalTrials.gov NCT00009737 (Hoffmann-La Roche, organisation study id M66001) lists phase 3 and an actual enrolment of 1987; the abstracts state no phase, and PubMed classifies the 2012 report as Clinical Trial, Phase III.
- Primary endpoint
- DFS
- Arms
- Bolus fluorouracil plus leucovorin (control, n = 983): Bolus fluorouracil plus leucovorin (Mayo Clinic regimen) for 24 weeks
- Capecitabine (experimental, n = 1,004): Oral capecitabine 1250 mg/m2 twice daily on days 1-14 every 3 weeks for 24 weeks
- People
- Twelves C
RFSHR 0.86 (95% CI 0.74–0.99)DFSHR 0.88 (95% CI 0.77–1.01)OSHR 0.86 (95% CI 0.74–1.01)
Show the numbers
| Endpoint | Analysis | Capecitabine | Bolus fluorouracil plus leucovorin | Effect |
|---|---|---|---|---|
| RFSRandomised patients with resected stage III colon cancer (1987); the abstract does not label the analysis population for this comparison | primaryTwelves 2005 | — | — | HR 0.86 (95% CI 0.74–0.99)P=0.04Capecitabine versus fluorouracil plus leucovorin. The abstract reports the primary DFS result only as at least equivalent (intention-to-treat, P<0.001 for the comparison of the upper limit of the hazard ratio with the non-inferiority margin of 1.20) and gives no DFS hazard ratio in the 2005 report. Relapse-free survival is not the stated primary efficacy endpoint (disease-free survival is). |
| DFSITT population (capecitabine 1004, 5-FU/FA 983) | finalmedian follow-up 6.9 yearsTwelves 2012 | — | — | HR 0.88 (95% CI 0.77–1.01)The P value (< 0.0001) is for non-inferiority against the margin of 1.20, not for a difference between the arms. The abstract reports a preplanned multivariate analysis with P = 0.021 for DFS in favour of capecitabine. |
| OSITT population (capecitabine 1004, 5-FU/FA 983) | finalmedian follow-up 6.9 yearsTwelves 2012 | — | — | HR 0.86 (95% CI 0.74–1.01)The P value (< 0.001) is for non-inferiority against the margin of 1.14. The abstract reports a preplanned multivariate analysis with P = 0.020 for OS. |
| Endpoint | Analysis | Capecitabine | Bolus fluorouracil plus leucovorin | Effect |
|---|---|---|---|---|
| RFSRandomised patients with resected stage III colon cancer (1987); the abstract does not label the analysis population for this comparison | primaryTwelves 2005 | — | — | HR 0.86 (95% CI 0.74–0.99)P=0.04Capecitabine versus fluorouracil plus leucovorin. The abstract reports the primary DFS result only as at least equivalent (intention-to-treat, P<0.001 for the comparison of the upper limit of the hazard ratio with the non-inferiority margin of 1.20) and gives no DFS hazard ratio in the 2005 report. Relapse-free survival is not the stated primary efficacy endpoint (disease-free survival is). |
| DFSITT population (capecitabine 1004, 5-FU/FA 983) | finalmedian follow-up 6.9 yearsTwelves 2012 | — | — | HR 0.88 (95% CI 0.77–1.01)The P value (< 0.0001) is for non-inferiority against the margin of 1.20, not for a difference between the arms. The abstract reports a preplanned multivariate analysis with P = 0.021 for DFS in favour of capecitabine. |
| OSITT population (capecitabine 1004, 5-FU/FA 983) | finalmedian follow-up 6.9 yearsTwelves 2012 | — | — | HR 0.86 (95% CI 0.74–1.01)The P value (< 0.001) is for non-inferiority against the margin of 1.14. The abstract reports a preplanned multivariate analysis with P = 0.020 for OS. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| RFS | 0.86 | 0.74–0.99 |
| DFS | 0.88 | 0.77–1.01 |
| OS | 0.86 | 0.74–1.01 |
Appears in
Sources
Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005;352(26):2696-704.
Twelves C, Scheithauer W, McKendrick J, Seitz JF, Van Hazel G, Wong A, et al. Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy. Ann Oncol. 2012;23(5):1190-1197.