A Randomised Trial of Preoperative Radiotherapy for Stage T3 Adenocarcinoma of Rectum

NCT ID: NCT00145769

Last Updated: 2013-08-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

326 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-07-31

Study Completion Date

2011-05-31

Brief Summary

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This is a multi-centre randomised trial comparing long course (LC) preoperative chemoradiation with short course (SC) preoperative radiotherapy for patients with localised T3 rectal cancer.

Detailed Description

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Objective:

* The objective is, in patients with T3 clinically resectable carcinoma of the rectum, to demonstrate that the local recurrence rate in patients treated with a long course (LC) of pre-operative radiotherapy with continuous infusion 5-FU is lower than that in patients treated with a short course (SC) of pre-operative radiotherapy with early surgery

Eligibility Criteria:

* The main eligibility criteria are that the patient has clinically resectable adenocarcinoma of the rectum, a clinical stage T3 tumour whose lower border is within 12 cm of the anal verge, and no evidence of distant metastases.

Endpoints:

* Primary endpoint is local recurrence.
* Secondary endpoints are overall survival, toxicity, abdminoperineal resection rate, quality of life.

Treatment arms:

* SC arm: Radiotherapy (RT) 25 Gy in 5 fr in 1 week to be followed by surgery within 1 week and 6 cycles of postoperative chemotherapy 5FU/Folinic acid.
* LC arm: RT 50.4 Gy in 28 fr in 5½weeks with 5FU 225 mg/m2/day throughout the course of RT, to be followed by surgery 4-6 weeks after completion of RT. 4 cycles of adjuvant 5FU/Folinic acid will be given.

Conditions

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Adenocarcinoma of Rectum

Keywords

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rectal cancer radiotherapy chemotherapy chemoradiation adjuvant therapy

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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Short Course Radiotherapy

Short Course (SC) pre-operative radiotherapy, followed by surgery and adjuvant chemotherapy

Group Type ACTIVE_COMPARATOR

Short Course Adjuvent Chemotherapy

Intervention Type DRUG

Post operative adjuvant chemotherapy: 5FU (425mg/m2) preceded by Folinic acid (20mg/m2) delivered over 5 days for 6 monthly cycles

Short Course Radiotherapy

Intervention Type RADIATION

25 Gy in 5 fractions over 5 days.

Long Course Radiotherapy

Long Course (LC) radiotherapy delivered with concurrent chemotherapy, followed by surgery and adjuvant chemotherapy

Group Type ACTIVE_COMPARATOR

Long Course Adjuvant Chemotherapy

Intervention Type DRUG

Post operative adjuvant 5FU (425mg/m2) preceded by folinic acid (20mg/m2) delivered over 5 days for 4 monthly cycles

Long Course Radiotherapy

Intervention Type RADIATION

50.4 Gy delivered in 1.8 Gy fractions over 5 1/2 weeks.

Concurrent Chemotherapy

Intervention Type DRUG

5FU 225mg/m2/day delivered IV over continous 7 day period for the duration of radiotherapy (5 1/2 weeks).

Surgery

Patients will receive initial surgery followed by post-operative management according to the NHMRC Guidelines for the prevention, early detection and management of colorectal cancer: Adjuvant therapy for rectal cancer.

Group Type ACTIVE_COMPARATOR

Initial Surgery

Intervention Type PROCEDURE

Surgery is to be performed according to the NHMRC Guidelines for the prevention, early detection and management of colorectal cancer: Elective surgery for rectal cancer

Interventions

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Short Course Adjuvent Chemotherapy

Post operative adjuvant chemotherapy: 5FU (425mg/m2) preceded by Folinic acid (20mg/m2) delivered over 5 days for 6 monthly cycles

Intervention Type DRUG

Long Course Adjuvant Chemotherapy

Post operative adjuvant 5FU (425mg/m2) preceded by folinic acid (20mg/m2) delivered over 5 days for 4 monthly cycles

Intervention Type DRUG

Short Course Radiotherapy

25 Gy in 5 fractions over 5 days.

Intervention Type RADIATION

Long Course Radiotherapy

50.4 Gy delivered in 1.8 Gy fractions over 5 1/2 weeks.

Intervention Type RADIATION

Concurrent Chemotherapy

5FU 225mg/m2/day delivered IV over continous 7 day period for the duration of radiotherapy (5 1/2 weeks).

Intervention Type DRUG

Initial Surgery

Surgery is to be performed according to the NHMRC Guidelines for the prevention, early detection and management of colorectal cancer: Elective surgery for rectal cancer

Intervention Type PROCEDURE

Other Intervention Names

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Radiation RT Short Course Radiation RT Long Course

Eligibility Criteria

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Inclusion Criteria

All of the following must apply:

* Pathologically documented and clinically resectable adenocarcinoma of the rectum.
* The patient must be considered by the surgeon to be suitable for a curative resection.
* The patient must be considered by the radiation oncologist to have no contraindication to pre-operative radiotherapy.
* Clinical T3 stage tumour on endorectal ultrasound or MRI. When endorectal ultrasound cannot be performed satisfactorily due to a technical reason, such as stenosis or proximity of the tumour, and MRI is not available, infiltration of perirectal fat on CT scan is also acceptable.
* Tumour with lower border within 12 cm from anal verge on rigid sigmoidoscopy.
* ECOG performance status 0, 1 or 2.
* Adequate bone marrow function with neutrophil count at least 1.5 x 109/L and platelet count at least 100 x 109/L.
* Adequate liver function with bilirubin and alanine aminotransferase (ALT) \<= 1.5 times the upper limit of normal.
* Adequate renal function with serum creatinine \<= 1.5 times the upper limit of normal.
* Accessibility for treatment and follow-up.
* Written informed consent.

Exclusion Criteria

* None of the following must apply:
* Evidence of distant metastases.
* Recurrent rectal cancer.
* Unstable cardiac disease or clinically significant active infection.
* Other cancer in the last 5 years except treated non-melanoma skin cancer or carcinoma in situ of the cervix.
* Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures.
* Contraindication to insertion of a suitable indwelling venous catheter e.g. implantable central venous device (infuse-a-port), Hickman catheter or peripherally inserted central catheter.
* Prior pelvic or abdominal radiotherapy.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Australasian Gastro-Intestinal Trials Group

NETWORK

Sponsor Role collaborator

Colorectal Surgical Society of Australasia (CSSA)

UNKNOWN

Sponsor Role collaborator

Royal Australasian College of Surgeons (RACS)

UNKNOWN

Sponsor Role collaborator

Trans Tasman Radiation Oncology Group

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sam Ngan, FRANZCR

Role: STUDY_CHAIR

Peter MacCallum Cancer Centre, Australia

Locations

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The Canberra Hospital

Garran, Australian Capital Territory, Australia

Site Status

Macarthur Cancer Therapy Centre

Campbelltown, New South Wales, Australia

Site Status

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status

Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

Newcastle Mater Misericordiae Hospital

Newcastle, New South Wales, Australia

Site Status

Nepean Cancer Care Centre

Penrith, New South Wales, Australia

Site Status

Prince of Wales Hospital

Randwick, New South Wales, Australia

Site Status

Royal North Shore Hospital

Sydney, New South Wales, Australia

Site Status

Riverina Cancer Care Centre

Wagga Wagga, New South Wales, Australia

Site Status

Westmead Hospital

Wentworthville, New South Wales, Australia

Site Status

Mater Private Hospital

Brisbane, Queensland, Australia

Site Status

Royal Brisbane Hospital

Herston, Queensland, Australia

Site Status

Mater QRI

South Brisbane, Queensland, Australia

Site Status

North Queensland Oncology Service

Townsville, Queensland, Australia

Site Status

East Coast Cancer Centre

Tugun, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Launceston General Hospital

Launceston, Tasmania, Australia

Site Status

Peter MacCallum Cancer Centre

Bendigo, Victoria, Australia

Site Status

Box Hill Hospital

Box Hill, Victoria, Australia

Site Status

Monash Medical Centre

East Bentleigh, Victoria, Australia

Site Status

Peter MacCallum Cancer Centre

East Melbourne, Victoria, Australia

Site Status

St Vincents Melbourne

Fitzroy, Victoria, Australia

Site Status

Western Hospital

Footscray, Victoria, Australia

Site Status

Frankston Hospital

Frankston, Victoria, Australia

Site Status

Andrew Love Cancer Centre, Geelong Hospital

Geelong, Victoria, Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

Alfred Hospital

Prahran, Victoria, Australia

Site Status

Murray Valley Private Hospital

Wodonga, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

Auckland Hospital

Auckland, , New Zealand

Site Status

Waikato Hospital

Hamilton, , New Zealand

Site Status

Wellington Hospital

Wellington, , New Zealand

Site Status

Countries

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Australia New Zealand

References

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Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46. doi: 10.1056/NEJMoa010580.

Reference Type BACKGROUND
PMID: 11547717 (View on PubMed)

Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005 Aug 20;23(24):5644-50. doi: 10.1200/JCO.2005.08.144.

Reference Type BACKGROUND
PMID: 16110023 (View on PubMed)

Ngan SY, Fisher R, Burmeister BH, Mackay J, Goldstein D, Kneebone A, Schache D, Joseph D, McKendrick J, Leong T, McClure B, Rischin D. Promising results of a cooperative group phase II trial of preoperative chemoradiation for locally advanced rectal cancer (TROG 9801). Dis Colon Rectum. 2005 Jul;48(7):1389-96. doi: 10.1007/s10350-005-0032-x.

Reference Type BACKGROUND
PMID: 15906126 (View on PubMed)

Ansari N, Solomon MJ, Fisher RJ, Mackay J, Burmeister B, Ackland S, Heriot A, Joseph D, McLachlan SA, McClure B, Ngan SY. Acute Adverse Events and Postoperative Complications in a Randomized Trial of Preoperative Short-course Radiotherapy Versus Long-course Chemoradiotherapy for T3 Adenocarcinoma of the Rectum: Trans-Tasman Radiation Oncology Group Trial (TROG 01.04). Ann Surg. 2017 May;265(5):882-888. doi: 10.1097/SLA.0000000000001987.

Reference Type DERIVED
PMID: 27631775 (View on PubMed)

Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. doi: 10.1200/JCO.2012.42.9597. Epub 2012 Sep 24.

Reference Type DERIVED
PMID: 23008301 (View on PubMed)

Related Links

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http://www.trog.com.au

Click here for more information about this study on the TROG official website

Other Identifiers

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NHMRC 209123

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

TROG 01.04

Identifier Type: -

Identifier Source: org_study_id