Trial Outcomes & Findings for Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation. The RAPIDO Trial (NCT NCT01558921)
NCT ID: NCT01558921
Last Updated: 2026-05-01
Results Overview
DrTF = Either local or distant relapse or death caused by the rectal carcinoma whichever comes first. In case of nonrectal cancer related death patients will be censored at date of death. In case of a second primary tumour patients will be censored at the date of diagnosis of the second primary tumour. In case of local regrowth after wait \& watch strategy, followed by no resection or R2 resection, diagnosis local regrowth is taken. Patients lost to follow-up will be censored the last date of patient visit. Survival curves for Disease related Treatment Failure after 3 years of follow-up will be constructed using the method of Kaplan and Meier.
ACTIVE_NOT_RECRUITING
PHASE3
920 participants
3 years follow-up after surgery
2026-05-01
Participant Flow
June 2011-June 2016
Participant milestones
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
|---|---|---|
|
Randomisation
STARTED
|
468
|
452
|
|
Randomisation
COMPLETED
|
462
|
450
|
|
Randomisation
NOT COMPLETED
|
6
|
2
|
|
Eligible Patients
STARTED
|
462
|
450
|
|
Eligible Patients
COMPLETED
|
460
|
441
|
|
Eligible Patients
NOT COMPLETED
|
2
|
9
|
|
Started Allocated Treatment
STARTED
|
460
|
441
|
|
Started Allocated Treatment
COMPLETED
|
426
|
400
|
|
Started Allocated Treatment
NOT COMPLETED
|
34
|
41
|
|
Surgery With Curative Intention <6m
STARTED
|
426
|
400
|
|
Surgery With Curative Intention <6m
COMPLETED
|
423
|
398
|
|
Surgery With Curative Intention <6m
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
|---|---|---|
|
Randomisation
Withdrawal by Subject
|
3
|
1
|
|
Randomisation
Protocol Violation
|
3
|
1
|
|
Eligible Patients
Protocol Violation
|
1
|
7
|
|
Eligible Patients
Physician Decision
|
1
|
2
|
|
Started Allocated Treatment
patient refused surgery
|
6
|
5
|
|
Started Allocated Treatment
Death
|
1
|
3
|
|
Started Allocated Treatment
Withdrawal by Subject
|
0
|
1
|
|
Started Allocated Treatment
Lost to Follow-up
|
1
|
0
|
|
Started Allocated Treatment
Protocol Violation
|
14
|
11
|
|
Started Allocated Treatment
Lack of Efficacy
|
12
|
21
|
|
Surgery With Curative Intention <6m
Lack of Efficacy
|
3
|
2
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=462 Participants
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=450 Participants
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
Total
n=912 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62 years
n=462 Participants
|
62 years
n=450 Participants
|
62 years
n=912 Participants
|
|
Sex: Female, Male
Female
|
162 Participants
n=462 Participants
|
138 Participants
n=450 Participants
|
300 Participants
n=912 Participants
|
|
Sex: Female, Male
Male
|
300 Participants
n=462 Participants
|
312 Participants
n=450 Participants
|
612 Participants
n=912 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Netherlands
|
180 participants
n=462 Participants
|
180 participants
n=450 Participants
|
360 participants
n=912 Participants
|
|
Region of Enrollment
Sweden
|
168 participants
n=462 Participants
|
160 participants
n=450 Participants
|
328 participants
n=912 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=462 Participants
|
10 participants
n=450 Participants
|
20 participants
n=912 Participants
|
|
Region of Enrollment
Norway
|
12 participants
n=462 Participants
|
11 participants
n=450 Participants
|
23 participants
n=912 Participants
|
|
Region of Enrollment
Denmark
|
16 participants
n=462 Participants
|
12 participants
n=450 Participants
|
28 participants
n=912 Participants
|
|
Region of Enrollment
Slovenia
|
18 participants
n=462 Participants
|
17 participants
n=450 Participants
|
35 participants
n=912 Participants
|
|
Region of Enrollment
Spain
|
58 participants
n=462 Participants
|
60 participants
n=450 Participants
|
118 participants
n=912 Participants
|
PRIMARY outcome
Timeframe: 3 years follow-up after surgeryPopulation: 462+450 participants started were eligible 2 + 6 participants were ineligible or withdrew informed consent
DrTF = Either local or distant relapse or death caused by the rectal carcinoma whichever comes first. In case of nonrectal cancer related death patients will be censored at date of death. In case of a second primary tumour patients will be censored at the date of diagnosis of the second primary tumour. In case of local regrowth after wait \& watch strategy, followed by no resection or R2 resection, diagnosis local regrowth is taken. Patients lost to follow-up will be censored the last date of patient visit. Survival curves for Disease related Treatment Failure after 3 years of follow-up will be constructed using the method of Kaplan and Meier.
Outcome measures
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=462 Participants
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=450 Participants
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
Standard of Care Group Without Post-operative Chemotherapy
Standard of care group without post-operative chemotherapy Chemoradiation -\> surgery
|
|---|---|---|---|
|
Number of Patients With Disease Related Treatment Failure (DrTF)
DrTF after 3 year FUP
|
128 Participants
|
152 Participants
|
—
|
|
Number of Patients With Disease Related Treatment Failure (DrTF)
no DrTF after 3 year FUP
|
334 Participants
|
298 Participants
|
—
|
SECONDARY outcome
Timeframe: 30 days after neoadjuvant treatmentPopulation: 901 of the 920 patients were evaluable
Number of patients in the experimental arm receiving 5 fractions of x 5 Gy (5x5Gy) radiotherapy followed by at least 75% of the prescribed chemotherapy. In the standard arm receiving the prescribed chemoradiotherapy.
Outcome measures
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=460 Participants
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=441 Participants
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
Standard of Care Group Without Post-operative Chemotherapy
Standard of care group without post-operative chemotherapy Chemoradiation -\> surgery
|
|---|---|---|---|
|
Number of Patients Completing the Prescribe Neo-adjuvant Treatment Dose
received at least 75% of the prescribed chemotherapy
|
386 Participants
|
410 Participants
|
—
|
|
Number of Patients Completing the Prescribe Neo-adjuvant Treatment Dose
received less than 75 % of the prescribed neoadjuvant treatment
|
74 Participants
|
31 Participants
|
—
|
SECONDARY outcome
Timeframe: 30 days after surgeryPopulation: Patients with a resection within 6 months after the end of preoperative treatment
Number of patients with a Circumferential Resection Margin (CRM) \> 1 mm
Outcome measures
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=423 Participants
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=398 Participants
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
Standard of Care Group Without Post-operative Chemotherapy
Standard of care group without post-operative chemotherapy Chemoradiation -\> surgery
|
|---|---|---|---|
|
Number of Patients With Negative CRM Negative
CRM > 1mm
|
385 Participants
|
363 Participants
|
—
|
|
Number of Patients With Negative CRM Negative
CRM <= 1 mm
|
38 Participants
|
35 Participants
|
—
|
SECONDARY outcome
Timeframe: 30 days after surgeryPopulation: Participants with a resection within 6 months after the end of preoperative treatment
Number of patients with a Pathological Complete Response (pCR) after neo-adjuvant treatment
Outcome measures
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=423 Participants
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=398 Participants
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
Standard of Care Group Without Post-operative Chemotherapy
Standard of care group without post-operative chemotherapy Chemoradiation -\> surgery
|
|---|---|---|---|
|
Number of Patients With a Pathological Complete Response (pCR)
Pathological complete response (pCR)
|
120 Participants
|
57 Participants
|
—
|
|
Number of Patients With a Pathological Complete Response (pCR)
No pCR
|
303 Participants
|
341 Participants
|
—
|
SECONDARY outcome
Timeframe: 30 days after surgeryPopulation: Patients undergoing standard surgery with curative intention
Number of patients with surgical complications: wound rupture, bleeding, infection, rectal anastomotic leak
Outcome measures
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=426 Participants
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=400 Participants
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
Standard of Care Group Without Post-operative Chemotherapy
Standard of care group without post-operative chemotherapy Chemoradiation -\> surgery
|
|---|---|---|---|
|
Number of Patients With Surgical Complications
Patients with 1 or more surgical complication >=CD grade III Clavien Dindo
|
63 Participants
|
55 Participants
|
—
|
|
Number of Patients With Surgical Complications
Patients without surgical complication >=CD grade III Clavien Dindo
|
363 Participants
|
345 Participants
|
—
|
SECONDARY outcome
Timeframe: 3 year after surgeryPopulation: 574 Patients without DrTF at 3 years post surgery were eligible to receive the questionnaires 495 questionnaires were returned, 453 analyzed (completed within time lines)
Quality of life QLQ-C30 core questionnaire EORTC quality-of-life instrument for use in international clinical trials in oncology A total Quality of Life Questionnaire (QLQ) score can range from 0 to 88, higher score means worse outcome.
Outcome measures
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=243 Participants
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=99 Participants
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
Standard of Care Group Without Post-operative Chemotherapy
n=111 Participants
Standard of care group without post-operative chemotherapy Chemoradiation -\> surgery
|
|---|---|---|---|
|
Quality of Life QLQ-C30 Scores
|
40.6 score on a scale
Standard Deviation 4.6
|
41.2 score on a scale
Standard Deviation 4.8
|
40.1 score on a scale
Standard Deviation 4.1
|
SECONDARY outcome
Timeframe: 3 year after surgeryPopulation: 574 Patients without DrTF at 3 years post surgery were eligible to receive the questionnaires 495 questionnaires were returned, 453 analyzed (completed within time lines)
Quality of life EORTC-QLQ-CIPN20. International EORTC questionnaire to assess Chemotherapy-Induced Peripheral Neuropathy (CIPN). A total QLQ-CIPN20 score can range from 0 to 100, higher score means worse outcome. Chemotherapy-induced peripheral neuropathy (CIPN) is a common phenomenon, often resulting in serious limitations in daily functioning and compromised quality of life.
Outcome measures
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=243 Participants
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=99 Participants
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
Standard of Care Group Without Post-operative Chemotherapy
n=111 Participants
Standard of care group without post-operative chemotherapy Chemoradiation -\> surgery
|
|---|---|---|---|
|
Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (EORTC-QLQ-CIPN20)
|
15.3 score on a scale
Standard Deviation 14.2
|
13.2 score on a scale
Standard Deviation 13.4
|
6 score on a scale
Standard Deviation 8
|
SECONDARY outcome
Timeframe: 3 year after surgeryPopulation: patients without a stoma three years after curative surgery
Low Anterior Resection Syndrome (LARS) scores in patients without a stoma three years after curative surgery Patient reported score (5 questions). 0-12 no LARS, 21-29 Minor LARS, 30-42 Major LARS. Higher scores mean a worse outcome.
Outcome measures
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=102 Participants
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=33 Participants
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
Standard of Care Group Without Post-operative Chemotherapy
n=40 Participants
Standard of care group without post-operative chemotherapy Chemoradiation -\> surgery
|
|---|---|---|---|
|
Quality of Life LARS Scores
No LARS
|
22 Participants
|
3 Participants
|
5 Participants
|
|
Quality of Life LARS Scores
Minor LARS
|
20 Participants
|
6 Participants
|
4 Participants
|
|
Quality of Life LARS Scores
Major LARS
|
60 Participants
|
24 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: 5 years after surgeryPopulation: 460+446 patients were resected. 431+428 underwent R0/R1 resection
Number of patients with a locoregional recurrence (LRR) after an R0/R1 resection
Outcome measures
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=431 Participants
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=428 Participants
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
Standard of Care Group Without Post-operative Chemotherapy
Standard of care group without post-operative chemotherapy Chemoradiation -\> surgery
|
|---|---|---|---|
|
Number of Patients With a Locoregional Recurrence
|
44 Participants
|
26 Participants
|
—
|
SECONDARY outcome
Timeframe: 10 yearOverall survival will be computed as the time between randomization and colorectal cancer or treatment related death. Patients lost to follow-up will be censored the last date of patient visit. In case of a second primary tumour patients will be censored at the date of diagnosis of the second primary tumour.
Outcome measures
Outcome data not reported
POST_HOC outcome
Timeframe: 5 years after surgeryPopulation: Eligible participants enrolled in the RAPIDO study
Number of patients with a diagnosis of the first appearance of distant metastases
Outcome measures
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=462 Participants
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=450 Participants
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
Standard of Care Group Without Post-operative Chemotherapy
Standard of care group without post-operative chemotherapy Chemoradiation -\> surgery
|
|---|---|---|---|
|
Number of Patients With Distant Metastases
Distant metastases
|
111 Participants
|
139 Participants
|
—
|
|
Number of Patients With Distant Metastases
No distant metastases
|
351 Participants
|
311 Participants
|
—
|
Adverse Events
B: 5x5Gy -> CAPOX -> Surgery
A: 5 Weeks Chemoradiation -> Surgery
Serious adverse events
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=460 participants at risk
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=441 participants at risk
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
|---|---|---|
|
Gastrointestinal disorders
grade 4+5 AEs
|
6.7%
31/460 • Number of events 31 • 3 years
|
2.9%
13/441 • Number of events 13 • 3 years
|
Other adverse events
| Measure |
B: 5x5Gy -> CAPOX -> Surgery
n=460 participants at risk
experimental group (arm B) M1 scheme
M1 scheme: short course 5 x 5 Gy radiation scheme is followed by six cycles of combination chemotherapy (capecitabine and oxaliplatin (CAPOX)) and surgery. FOLFOX4 may be given as alternative for CAPOX
|
A: 5 Weeks Chemoradiation -> Surgery
n=441 participants at risk
control group (arm A) standard long course chemoradiotherapy
standard long course chemoradiotherapy: long course chemoradiotherapy followed by surgery. Optional adjuvant chemotherapy (CAPOX or FOLFOX) is allowed in the control group.
|
|---|---|---|
|
Gastrointestinal disorders
Grade 1-3 AEs
|
93.3%
429/460 • Number of events 429 • 3 years
|
95.5%
421/441 • Number of events 421 • 3 years
|
Additional Information
Annet Roodvoets, MSc, project coordinator
LUMC
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60