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

Condition(s) targeted: Adenocarcinoma of Rectum

Intervention: Short Course Adjuvent Chemotherapy (Drug); Long Course Adjuvant Chemotherapy (Drug); Short Course Radiotherapy (Radiation); Long Course Radiotherapy (Radiation); Concurrent Chemotherapy (Drug); Initial Surgery (Procedure)

Phase: Phase 3

Status: Completed

Sponsored by: Trans-Tasman Radiation Oncology Group (TROG)

Official(s) and/or principal investigator(s):
Sam Ngan, FRANZCR, Study Chair, Affiliation: Peter MacCallum Cancer Centre, Australia

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.

Official title: A Randomised Trial of Preoperative Radiotherapy for Stage T3 Adenocarcinoma of Rectum

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Local recurrence

Secondary outcome:

Survival

Toxicity

Abdominoperineal resection rate. This is defined as the proportion of all patients in any arm who undergo operation by abdominalperineal resection.

Quality of life

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Auckland Hospital, Auckland 1001, New Zealand

Waikato Hospital, Hamilton 3200, New Zealand

Wellington Hospital, Wellington 7902, New Zealand

The Canberra Hospital, Garran, Australian Capital Territory 2605, Australia

Macarthur Cancer Therapy Centre, Campbelltown, New South Wales 2560, Australia

Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia

Liverpool Hospital, Liverpool, New South Wales 1871, Australia

Newcastle Mater Misericordiae Hospital, Newcastle, New South Wales 2310, Australia

Nepean Cancer Care Centre, Penrith, New South Wales 2751, Australia

Prince of Wales Hospital, Randwick, New South Wales 2031, Australia

Royal North Shore Hospital, Sydney, New South Wales 2069, Australia

Riverina Cancer Care Centre, Wagga Wagga, New South Wales 2650, Australia

Westmead Hospital, Wentworthville, New South Wales 2145, Australia

Mater Private Hospital, Brisbane, Queensland, Australia

Royal Brisbane Hospital, Herston, Queensland 4029, Australia

Mater QRI, South Brisbane, Queensland 4101, Australia

North Queensland Oncology Service, Townsville, Queensland 4810, Australia

East Coast Cancer Centre, Tugun, Queensland 4224, Australia

Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia

Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia

Launceston General Hospital, Launceston, Tasmania 7250, Australia

Peter MacCallum Cancer Centre, Bendigo, Victoria, Australia

Box Hill Hospital, Box Hill, Victoria, Australia

Monash Medical Centre, East Bentleigh, Victoria 3165, Australia

Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia

St Vincents Melbourne, Fitzroy, Victoria, Australia

Western Hospital, Footscray, Victoria, Australia

Frankston Hospital, Frankston, Victoria, Australia

Andrew Love Cancer Centre, Geelong Hospital, Geelong, Victoria 3220, Australia

Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia

Alfred Hospital, Prahran, Victoria 3181, Australia

Murray Valley Private Hospital, Wodonga, Victoria 3690, Australia

Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009, Australia

Royal Perth Hospital, Perth, Western Australia 6000, Australia

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

Related publications:

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.

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.

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.

Starting date: July 2001
Last updated: August 7, 2013