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

This study has been completed.
Sponsor:
Collaborators:
Australasian Gastro-Intestinal Trials Group
Colorectal Surgical Society of Australasia (CSSA)
Royal Australasian College of Surgeons (RACS)
Information provided by (Responsible Party):
Trans-Tasman Radiation Oncology Group (TROG)
ClinicalTrials.gov Identifier:
NCT00145769
First received: September 2, 2005
Last updated: August 7, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of Rectum
Drug: Short Course Adjuvent Chemotherapy
Drug: Long Course Adjuvant Chemotherapy
Radiation: Short Course Radiotherapy
Radiation: Long Course Radiotherapy
Drug: Concurrent Chemotherapy
Procedure: Initial Surgery
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Trial of Preoperative Radiotherapy for Stage T3 Adenocarcinoma of Rectum

Resource links provided by NLM:


Further study details as provided by Trans-Tasman Radiation Oncology Group (TROG):

Primary Outcome Measures:
  • Local recurrence [ Time Frame: Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival [ Time Frame: Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial) ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Interim analyses will occur annually. ] [ Designated as safety issue: Yes ]
  • Abdominoperineal resection rate. This is defined as the proportion of all patients in any arm who undergo operation by abdominalperineal resection. [ Time Frame: Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial) ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial) ] [ Designated as safety issue: No ]

Enrollment: 326
Study Start Date: July 2001
Study Completion Date: May 2011
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Short Course Radiotherapy
Short Course (SC) pre-operative radiotherapy, followed by surgery and adjuvant chemotherapy
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
Radiation: Short Course Radiotherapy
25 Gy in 5 fractions over 5 days.
Other Names:
  • Radiation
  • RT
  • Short Course
Active Comparator: Long Course Radiotherapy
Long Course (LC) radiotherapy delivered with concurrent chemotherapy, followed by surgery and adjuvant chemotherapy
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
Radiation: Long Course Radiotherapy
50.4 Gy delivered in 1.8 Gy fractions over 5 1/2 weeks.
Other Names:
  • Radiation
  • RT
  • Long Course
Drug: Concurrent Chemotherapy
5FU 225mg/m2/day delivered IV over continous 7 day period for the duration of radiotherapy (5 1/2 weeks).
Active Comparator: 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.
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00145769

Locations
Australia, Australian Capital Territory
The Canberra Hospital
Garran, Australian Capital Territory, Australia, 2605
Australia, New South Wales
Macarthur Cancer Therapy Centre
Campbelltown, New South Wales, Australia, 2560
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
Liverpool Hospital
Liverpool, New South Wales, Australia, 1871
Newcastle Mater Misericordiae Hospital
Newcastle, New South Wales, Australia, 2310
Nepean Cancer Care Centre
Penrith, New South Wales, Australia, 2751
Prince of Wales Hospital
Randwick, New South Wales, Australia, 2031
Royal North Shore Hospital
Sydney, New South Wales, Australia, 2069
Riverina Cancer Care Centre
Wagga Wagga, New South Wales, Australia, 2650
Westmead Hospital
Wentworthville, New South Wales, Australia, 2145
Australia, Queensland
Mater Private Hospital
Brisbane, Queensland, Australia
Royal Brisbane Hospital
Herston, Queensland, Australia, 4029
Mater QRI
South Brisbane, Queensland, Australia, 4101
North Queensland Oncology Service
Townsville, Queensland, Australia, 4810
East Coast Cancer Centre
Tugun, Queensland, Australia, 4224
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Tasmania
Launceston General Hospital
Launceston, Tasmania, Australia, 7250
Australia, Victoria
Peter MacCallum Cancer Centre
Bendigo, Victoria, Australia
Box Hill Hospital
Box Hill, Victoria, Australia
Monash Medical Centre
East Bentleigh, Victoria, Australia, 3165
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
St Vincents Melbourne
Fitzroy, Victoria, Australia
Western Hospital
Footscray, Victoria, Australia
Frankston Hospital
Frankston, Victoria, Australia
Andrew Love Cancer Centre, Geelong Hospital
Geelong, Victoria, Australia, 3220
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia, 3002
Alfred Hospital
Prahran, Victoria, Australia, 3181
Murray Valley Private Hospital
Wodonga, Victoria, Australia, 3690
Australia, Western Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, Australia, 6009
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
New Zealand
Auckland Hospital
Auckland, New Zealand, 1001
Waikato Hospital
Hamilton, New Zealand, 3200
Wellington Hospital
Wellington, New Zealand, 7902
Sponsors and Collaborators
Trans-Tasman Radiation Oncology Group (TROG)
Australasian Gastro-Intestinal Trials Group
Colorectal Surgical Society of Australasia (CSSA)
Royal Australasian College of Surgeons (RACS)
Investigators
Study Chair: Sam Ngan, FRANZCR Peter MacCallum Cancer Centre, Australia
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Trans-Tasman Radiation Oncology Group (TROG)
ClinicalTrials.gov Identifier: NCT00145769     History of Changes
Other Study ID Numbers: TROG 01.04, NHMRC 209123
Study First Received: September 2, 2005
Last Updated: August 7, 2013
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Trans-Tasman Radiation Oncology Group (TROG):
rectal cancer
radiotherapy
chemotherapy
chemoradiation
adjuvant therapy

Additional relevant MeSH terms:
Adenocarcinoma
Rectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on September 18, 2014