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

Adenocarcinoma of Rectum Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00145769
• Other study ID #: TROG 01.04
• Secondary ID: NHMRC 209123
• Status: Completed
• Phase: Phase 3
• First received: September 2, 2005
• Last updated: August 7, 2013
• Start date: July 2001
• Est. completion date: May 2011

Study information

• Verified date: August 2013
• Source: Trans-Tasman Radiation Oncology Group (TROG)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 326
• Est. completion date: May 2011
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Rectum
• Rectal Neoplasms

Intervention

Drug:
• 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
• Long Course Adjuvant Chemotherapy
Post operative adjuvant 5FU (425mg/m2) preceded by folinic acid (20mg/m2) delivered over 5 days for 4 monthly cycles

Radiation:
• Short Course Radiotherapy
25 Gy in 5 fractions over 5 days.
• Long Course Radiotherapy
50.4 Gy delivered in 1.8 Gy fractions over 5 1/2 weeks.

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

Procedure:
• 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

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Peter MacCallum Cancer Centre	Bendigo	Victoria
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Mater Private Hospital	Brisbane	Queensland
Australia	Macarthur Cancer Therapy Centre	Campbelltown	New South Wales
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Medical Centre	East Bentleigh	Victoria
Australia	Peter MacCallum Cancer Centre	East Melbourne	Victoria
Australia	St Vincents Melbourne	Fitzroy	Victoria
Australia	Western Hospital	Footscray	Victoria
Australia	Frankston Hospital	Frankston	Victoria
Australia	The Canberra Hospital	Garran	Australian Capital Territory
Australia	Andrew Love Cancer Centre, Geelong Hospital	Geelong	Victoria
Australia	Royal Brisbane Hospital	Herston	Queensland
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Newcastle Mater Misericordiae Hospital	Newcastle	New South Wales
Australia	Nepean Cancer Care Centre	Penrith	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Alfred Hospital	Prahran	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Mater QRI	South Brisbane	Queensland
Australia	Royal North Shore Hospital	Sydney	New South Wales
Australia	North Queensland Oncology Service	Townsville	Queensland
Australia	East Coast Cancer Centre	Tugun	Queensland
Australia	Riverina Cancer Care Centre	Wagga Wagga	New South Wales
Australia	Westmead Hospital	Wentworthville	New South Wales
Australia	Murray Valley Private Hospital	Wodonga	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
New Zealand	Auckland Hospital	Auckland
New Zealand	Waikato Hospital	Hamilton
New Zealand	Wellington Hospital	Wellington

Sponsors (4)

Lead Sponsor	Collaborator
Trans-Tasman Radiation Oncology Group (TROG)	Australasian Gastro-Intestinal Trials Group, Colorectal Surgical Society of Australasia (CSSA), Royal Australasian College of Surgeons (RACS)

Countries where clinical trial is conducted

Australia,  New Zealand, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local recurrence		Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial)	No
Secondary	Survival		Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial)	No
Secondary	Toxicity		Interim analyses will occur annually.	Yes
Secondary	Abdominoperineal resection rate. This is defined as the proportion of all patients in any arm who undergo operation by abdominalperineal resection.		Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial)	No
Secondary	Quality of life		Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial)	No

External Links

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