Background - For locally advanced rectal cancer the 5-year overall survival rate remains below 70%. Even with improved rates of local control in rectal cancer; no recent improvements have been seen for distant recurrence or overall survival. The addition of oxaliplatin improved disease-free survival in colon cancer; so the important question that is addressed in this study is- is this also true for rectal cancer.

It is thought that a combination chemotherapy regimen with capecitabine and oxaliplatin instead of a single agent regimen may improve overall outcome due to its potentially higher impact on micrometastases as is has already been proven to do so in stage III colon cancer.

Capecitabine was chosen as a substitute for IV 5-FU for all treatment arms of the study as it is already proven that 5-FU and capecitabine show similar results in complete response and disease survival rates for stage III CRC, however capecitabine offers reduced toxicity. The addition of oxaliplatin to capecitabine has shown to be efficacious and safe in phase II trials of preoperative chemoradiotherapy and in large phase III trials for stage II/III colon cancer.

Study Design - The PETACC-6 study is an open-label, randomised, multi-national, two-arm phase III study. Eligible patients will be randomised to one of two treatment arms. The control arm is capecitabine with radiotherapy before surgery, followed by capecitabine after surgery. The investigational arm is capecitabine with oxaliplatin and radiotherapy before surgery, followed by capecitabine and oxaliplatin after surgery.

Objectives - The study’s objectives are to investigate whether the addition of oxaliplatin to preoperative fluoropyrimidine-based chemoradiation and postoperative fluoropyrimidine-based chemotherapy improves disease-free survival in locally advanced rectal cancer.  Disease-free survival is defined as the interval from randomization to loco-regional failure, metastatic recurrence, the appearance of a secondary colorectal cancer or death, whichever occurs first.

Secondary objectives in this study are to compare the two treatment arms with respect to overall survival, pathological downstaging (ypT0-T2N0) rate, pathological complete remission rate, histopathological R0 resection rate, sphincter preservation rate, perioperative surgical complication rate, toxicity, loco-regional failure rate and distant metastases.

Study Progress - PETACC-6 was originally awarded a 3 year grant from Cancer Australia in 2008. In March 2010 an extension was granted by Cancer Australia and the project period now ends in April 2012.

Internationally the PETACC-6 trial opened to recruitment in November 2008. A total sample of 1090 patients have been recruited to the trial over 3 years.Across Australia and New Zealand 21 sites have opened to date, with the first Australian site opened on 22^nd April 2009. The first ANZ patient was recruited onto PETACC-6 on 26th May 2009 with 127 patients recruited in Australia and 135 patients recruited in New Zealand. Global recruitment for the study closed on 19^th September 2011 and there are currently 109 patients in follow up across ANZ.

Radiological Assessments and Quality Assurance (QA) Sub-study is being performing using MRIs of the rectum. This is a relatively new imaging test with significant variation in the experience of reporting radiologists around the country. Accurate reporting is vital to stratifying patients for appropriate treatment. This sub study offers the opportunity to audit the MRI technique and reporting of MRI rectal images at a variety of Australian & New Zealand sites.  The prospective report will be correlated with the findings of 1 or 2 central radiologists experienced in this area, surgical results and clinical outcome.  This will provide useful feedback to the radiology community about the current status of MRI rectal reporting in Australia and New Zealand.

At least 25% of the patients will be audited. Audit will be done by a central radiologist with specialisation in rectal MRI. The reliability of reporting may be tested by a second central radiologist, similarly qualified who will be blinded to the local and central radiologists report. Auditing will include MRI technique.88/127 MRIs were initially collected from patients but only 67/127 patients had both baseline and pre surgery MRIs collected. The retrieval of MRIs iscomplete and has been provided for review. 21 of the 67 scans have been reviewed by the first reader and the second reader has reviewed 8. The readers aim to have them all finished by the end of September or mid October for an article to be submitted to JMIRO (Journal of Medical imaging and Radiation oncology) - Australian RANZCR college.

Early toxicity results have been presented at ASCO and ESMO and an update on this information will be presented at the meeting. Importantly tissue collection continues and is a current priority as t will allow the Australian group to have input in proposed translational studies.

Translational research – Consent for FFPE tumour tissue collection was optional. Tissue collection is ongoing in Australia.

International sites are collecting bloods (buffy coat and plasma) for research at  3 time points (baseline, pre-surgery, recurrence). Australia is not participating in collection of research bloods.