The Stockholm III Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer

NCT ID: NCT00904813

Last Updated: 2021-05-07

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

840 participants

Study Classification

INTERVENTIONAL

Study Start Date

1998-11-30

Study Completion Date

2018-03-31

Brief Summary

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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

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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

Conditions

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Rectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1. Short-course RT (5x5 Gy) + surgery within 1 week (SRT)

RT=Preoperative radiotherapy Gy=Gray

Group Type ACTIVE_COMPARATOR

Short-course RT

Intervention Type RADIATION

Preoperative radiotherapy (RT) given 5 times 5 Gray during five consecutive days, preferably Monday - Friday, with a four-field box technique, including the primary tumour and the primary and secondary lymph nodes in the pelvis.

2. Short-course RT (5x5 Gy) + surgery after 4-8 weeks (SRT-delay)

RT=Preoperative radiotherapy Gy= Gray

Group Type ACTIVE_COMPARATOR

Short-course RT

Intervention Type RADIATION

Preoperative radiotherapy (RT) given 5 times 5 Gray during five consecutive days, preferably Monday - Friday, with a four-field box technique, including the primary tumour and the primary and secondary lymph nodes in the pelvis.

3. Long-course RT (25x2 Gy) + surgery after 4-8 weeks (LRT-delay)

RT= Preoperative radiotherapy Gy= Gray

Group Type ACTIVE_COMPARATOR

Long-course RT

Intervention Type RADIATION

Preoperative radiotherapy (RT) given 2 Gy in 25 fractions during 5 weeks, total dose 50 Gy with a four-field box technique, including the primary tumour and the primary and secondary lymph nodes in the pelvis.

Interventions

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Short-course RT

Preoperative radiotherapy (RT) given 5 times 5 Gray during five consecutive days, preferably Monday - Friday, with a four-field box technique, including the primary tumour and the primary and secondary lymph nodes in the pelvis.

Intervention Type RADIATION

Long-course RT

Preoperative radiotherapy (RT) given 2 Gy in 25 fractions during 5 weeks, total dose 50 Gy with a four-field box technique, including the primary tumour and the primary and secondary lymph nodes in the pelvis.

Intervention Type RADIATION

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Swedish Cancer Society

OTHER

Sponsor Role collaborator

The Swedish Research Council

OTHER_GOV

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role lead

Responsible Party

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Anna Martling

Professor, Senior Consultant Surgeon

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anna Martling, Professor

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Locations

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Mora Hospital

Mora, Dalarna County, Sweden

Site Status

Danderyds Hospital

Danderyd, Stockholm County, Sweden

Site Status

Norrtälje Hospital

Norrtälje, Stockholm County, Sweden

Site Status

Södertälje Hospital

Södertälje, Stockholm County, Sweden

Site Status

Eskilstuna Hospital

Eskilstuna, , Sweden

Site Status

Falun Hospital

Falun, , Sweden

Site Status

Gävle Sjukhus

Gävle, , Sweden

Site Status

Helsingborg Hospital

Helsingborg, , Sweden

Site Status

Linköping University Hospital

Linköping, , Sweden

Site Status

MAS University Hospital

Malmo, , Sweden

Site Status

Vrinnevi Hospital

Norrköping, , Sweden

Site Status

Karolinska University Hospital

Stockholm, , Sweden

Site Status

Ersta Hospital

Stockholm, , Sweden

Site Status

South Hospital

Stockholm, , Sweden

Site Status

St Görans Hospital

Stockholm, , Sweden

Site Status

Norrlands Universitetssjukhus

Umeå, , Sweden

Site Status

Uppsala University Hospital

Uppsala, , Sweden

Site Status

Visby Hospital

Visby, , Sweden

Site Status

Countries

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Sweden

References

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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.

Reference Type BACKGROUND
PMID: 26095256 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20155787 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23553796 (View on PubMed)

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.

Reference Type RESULT
PMID: 28190762 (View on PubMed)

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.

Reference Type RESULT
PMID: 31015165 (View on PubMed)

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.

Reference Type RESULT
PMID: 31197822 (View on PubMed)

Other Identifiers

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98/240

Identifier Type: -

Identifier Source: org_study_id

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