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

• ClinicalTrials.gov Identifier: NCT00145769
• Recruitment Status: Completed
• First Posted: September 5, 2005
• Last Update Posted: August 9, 2013
• Sponsor: Trans Tasman Radiation Oncology Group
• 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

Tracking Information

• First Submitted Date: September 2, 2005
• First Posted Date: September 5, 2005
• Last Update Posted Date: August 9, 2013
• Study Start Date: July 2001
• Actual Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 8, 2007): Local recurrence [ Time Frame: Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial) ]
• Original Primary Outcome Measures (submitted: September 2, 2005): - Local recurrence

Current Secondary Outcome Measures (submitted: May 8, 2007)

• Survival [ Time Frame: Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial) ]
• Toxicity [ Time Frame: Interim analyses will occur annually. ]
• 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) ]
• 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) ]

Original Secondary Outcome Measures (submitted: September 2, 2005)

• - Survival
• - Toxicity
• - Abdominoperineal resection rate
• - Quality of life

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Adenocarcinoma of Rectum

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
• 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: Short Course Radiotherapy
  25 Gy in 5 fractions over 5 days.
  Other Names:

  • Radiation
  • RT
  • Short Course
• 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).
• 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

Study Arms

• Active Comparator: Short Course Radiotherapy
  Short Course (SC) pre-operative radiotherapy, followed by surgery and adjuvant chemotherapy
  Interventions:

  • Drug: Short Course Adjuvent Chemotherapy
  • Radiation: Short Course Radiotherapy
• Active Comparator: Long Course Radiotherapy
  Long Course (LC) radiotherapy delivered with concurrent chemotherapy, followed by surgery and adjuvant chemotherapy
  Interventions:

  • Drug: Long Course Adjuvant Chemotherapy
  • Radiation: Long Course Radiotherapy
  • Drug: Concurrent Chemotherapy
• 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.
  Intervention: Procedure: Initial Surgery

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. doi: 10.1056/NEJMoa010580.
• 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.
• 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.
• 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.
• 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. Erratum In: J Clin Oncol. 2013 Jan 20;31(3):399.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 29, 2009): 326
• Original Enrollment (submitted: September 2, 2005): 325
• Actual Study Completion Date: May 2011
• Actual Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, New Zealand

Administrative Information

• NCT Number: NCT00145769
• Other Study ID Numbers: TROG 01.04; NHMRC 209123 ( Other Grant/Funding Number: National Health Medical and Research Council )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Trans Tasman Radiation Oncology Group
• Original Responsible Party: Not Provided
• Current Study Sponsor: Trans Tasman Radiation Oncology Group
• Original Study Sponsor: Same as current

Collaborators

• 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

• PRS Account: Trans Tasman Radiation Oncology Group
• Verification Date: August 2013