Clinical trial NCT00145769: A Randomised Trial of Preoperative Radiotherapy for Stage T3 Adenocarcinoma of Rectum
Official title: A Randomised Trial of Preoperative Radiotherapy for Stage T3 Adenocarcinoma of Rectum
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Adenocarcinoma of Rectum
Keywords: rectal cancer
radiotherapy
chemotherapy
chemoradiation
adjuvant therapy
Lead sponsor: Trans Tasman Radiation Oncology Group
Sponsor class: OTHER
Collaborators: name: Australasian Gastro-Intestinal Trials Group
name: Colorectal Surgical Society of Australasia (CSSA)
name: Royal Australasian College of Surgeons (RACS)
First posted: 2005-09-05
Enrollment: 326
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: 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: 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.

Eligibility 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.

Primary outcomes:
measure: Local recurrence
timeFrame: Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial)
Secondary outcomes:
measure: Survival
timeFrame: Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial)
measure: Toxicity
timeFrame: Interim analyses will occur annually.
measure: Abdominoperineal resection rate. This is defined as the proportion of all patients in any arm who undergo operation by abdominalperineal resection.
timeFrame: Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial)
measure: Quality of life
timeFrame: Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial)
Other outcomes:
Locations:
city: Garran
country: Australia
facility: The Canberra Hospital
state: Australian Capital Territory
city: Campbelltown
country: Australia
facility: Macarthur Cancer Therapy Centre
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: Newcastle Mater Misericordiae Hospital
state: New South Wales
city: Penrith
country: Australia
facility: Nepean Cancer Care Centre
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Wagga Wagga
country: Australia
facility: Riverina Cancer Care Centre
state: New South Wales
city: Wentworthville
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Mater Private Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater QRI
state: Queensland
city: Townsville
country: Australia
facility: North Queensland Oncology Service
state: Queensland
city: Tugun
country: Australia
facility: East Coast Cancer Centre
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Bendigo
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: East Bentleigh
country: Australia
facility: Monash Medical Centre
state: Victoria
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Fitzroy
country: Australia
facility: St Vincents Melbourne
state: Victoria
city: Footscray
country: Australia
facility: Western Hospital
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Geelong
country: Australia
facility: Andrew Love Cancer Centre, Geelong Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Prahran
country: Australia
facility: Alfred Hospital
state: Victoria
city: Wodonga
country: Australia
facility: Murray Valley Private Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Auckland
country: New Zealand
facility: Auckland Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
Study officials:
affiliation: Peter MacCallum Cancer Centre, Australia
name: Sam Ngan, FRANZCR
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.