Clinical trial NCT00904813: The Stockholm III Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer
Official title: A Prospective Randomized Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer, Stockholm III.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rectal Cancer
Keywords: Rectal cancer
Preoperative radiotherapy
Timing of Surgery
Prognosis
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Swedish Cancer Society
name: The Swedish Research Council
First posted: 2009-05-20
Enrollment: 840
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Preoperative radiotherapy (RT) is recommended to many patients with localised rectal cancer, not previously treated with pelvic RT. However, the optimum fractionation, the timing of surgery and the best use of concomitant chemotherapy remains controversial. There are theoretical reasons to believe that radiotherapy given in larger fractions during a shorter period of time might result in more late side effects than giving a conventional, more protracted RT in patients with rectal cancer. In addition, the optimum timing of surgery after RT, with respect to postoperative morbidity, mortality and potential downsizing of the tumour is not known.

To address these questions, a prospective randomized multicenter trial was initiated, the Stockholm III trial, in which patients with primarily resectable rectal cancer were randomized to short-course preoperative RT (5x5 Gy) followed by surgery within one week or after 4-8 weeks or long-course preoperative RT(25x2 Gy) followed by surgery after 4-8 weeks.

Detailed description: 840 participants (men and women) with a biopsy verified adenocarcinoma of the rectum scheduled for an open abdominal procedure were enrolled at 18 Swedish Hospitals during 1998-2013.

In the initial protocol patients were randomly assigned (1:1:1) between three different RT courses; 5x5 Gy with surgery within 1 week (SRT), 5x5 Gy with surgery after 4-8 weeks (SRT-delay) or 25x2 Gy during 5 weeks without concomitant chemotherapy and surgery after 4-8weeks (LRT-delay). After a protocol amendment on May 21, 1999, participating hospitals could choose to randomise patients to just the short-course radiotherapy arms (1:1) or to all three arms.

Randomisation was done by telephone by the Regional Cancer Centre in Stockholm, Sweden, after assessing inclusion and exclusion criteria. Computer generated randomisation lists were constructed by use of permuted block technique (block size of six for the three- arm randomisation, block size of four for the two-arm randomisation) and stratified by participating center. Investigators and patients were not masked to treatment.

Follow-up was recommended at 3-, 6- and 12 months after surgery, and yearly thereafter. Although follow-up according to national guidelines with a minimum follow-up at 1 and 3 years was allowed. Patient data was also collected from the Swedish ColoRectal Cancer Register (SCRCR) and medical records.

Primary outcome:

1. Time to local recurrence.

Secondary outcomes:

1. Recurrence-free survival
2. Frequency of postoperative complications
3. Frequency of tumour regression

Eligibility criteria: Inclusion Criteria:

* Biopsy confirmed clinically resectable rectal adenocarcinoma within 15 cm from the anal verge
* Planned for bowel resection with an abdominal procedure.
* Informed consent.

Exclusion Criteria:

* Distant metastases
* Locally advanced unresectable tumors
* Planned for local excision
* Previous radiotherapy to the abdominal or pelvic region
* Severe ischemic heart disease or symptoms of severe arteriosclerosis

Primary outcomes:
measure: Time to Local Recurrence.
timeFrame: From date of randomisation until date of local recurrence or date of death from any cause, whichever came first, assessed up to end of follow-up.
Secondary outcomes:
measure: Number of Participants With Postoperative Complications in Relation to Preoperative Radiotherapy Regimen and Overall Treatment Time.
timeFrame: From surgery until 30 days postoperatively.
measure: Tumour Regression Based on the Dworak Grading Scoring System
timeFrame: At the time of surgery.
Other outcomes:
Locations:
city: Mora
country: Sweden
facility: Mora Hospital
state: Dalarna
city: Danderyd
country: Sweden
facility: Danderyds Hospital
state: Stockholm
city: Norrtälje
country: Sweden
facility: Norrtälje Hospital
state: Stockholm
city: Södertälje
country: Sweden
facility: Södertälje Hospital
state: Stockholm
city: Eskilstuna
country: Sweden
facility: Eskilstuna Hospital
city: Falun
country: Sweden
facility: Falun Hospital
city: Gävle
country: Sweden
facility: Gävle Sjukhus
city: Helsingborg
country: Sweden
facility: Helsingborg Hospital
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Malmö
country: Sweden
facility: MAS University Hospital
city: Norrköping
country: Sweden
facility: Vrinnevi Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Ersta Hospital
city: Stockholm
country: Sweden
facility: South Hospital
city: Stockholm
country: Sweden
facility: St Görans Hospital
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Visby
country: Sweden
facility: Visby Hospital
Study officials:
affiliation: Karolinska Institutet
name: Anna Martling, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pettersson D, Lorinc E, Holm T, Iversen H, Cedermark B, Glimelius B, Martling A. Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer. Br J Surg. 2015 Jul;102(8):972-8; discussion 978. doi: 10.1002/bjs.9811.
citation: Pettersson D, Cedermark B, Holm T, Radu C, Pahlman L, Glimelius B, Martling A. Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg. 2010 Apr;97(4):580-7. doi: 10.1002/bjs.6914.
citation: Pettersson D, Glimelius B, Iversen H, Johansson H, Holm T, Martling A. Impaired postoperative leucocyte counts after preoperative radiotherapy for rectal cancer in the Stockholm III Trial. Br J Surg. 2013 Jun;100(7):969-75. doi: 10.1002/bjs.9117. Epub 2013 Apr 2.
citation: Erlandsson J, Holm T, Pettersson D, Berglund A, Cedermark B, Radu C, Johansson H, Machado M, Hjern F, Hallbook O, Syk I, Glimelius B, Martling A. Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial. Lancet Oncol. 2017 Mar;18(3):336-346. doi: 10.1016/S1470-2045(17)30086-4. Epub 2017 Feb 10.
citation: Erlandsson J, Lorinc E, Ahlberg M, Pettersson D, Holm T, Glimelius B, Martling A. Tumour regression after radiotherapy for rectal cancer - Results from the randomised Stockholm III trial. Radiother Oncol. 2019 Jun;135:178-186. doi: 10.1016/j.radonc.2019.03.016. Epub 2019 Apr 1.
citation: Erlandsson J, Pettersson D, Glimelius B, Holm T, Martling A. Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy. Br J Surg. 2019 Aug;106(9):1248-1256. doi: 10.1002/bjs.11200. Epub 2019 Jun 14.