• PETACC6
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Trial Status

Completed

Cancer Type

Colorectal Cancer

Protocol Title

Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer.

Purpose of the Study

The five–year survival rate for locally advanced rectal cancer is less than 70%. A combination chemotherapy treatment plan that includes the chemotherapy drugs capecitabine and oxaliplatin has been proven to have a beneficial effect in advanced colorectal cancer. Previous studies have also identified capecitabine to be a less toxic option. Therefore, a combination chemotherapy regimen – with capecitabine and oxaliplatin – instead of a treatment using a single drug may improve survival rates in rectal cancer.

PETACC-6 investigated whether adding the new chemotherapy drug oxaliplatin to pre-operative standard chemotherapy and radiotherapy – and post-operative standard chemotherapy can improve disease-free survival for patients with locally advanced rectal cancer.

Principal Investigator

Prof Tim Price

Basic Eligibility Criteria

Inclusion Criteria

  1. Male or female patients with histologically proven adenocarcinoma of the rectum
  2. No evidence of metastatic disease
  3. The disease must be considered either resectable at the time of entry or expected to become resectable after preoperative chemo-radiation
  4. Age = 18 years.
  5. No prior cytotoxic chemotherapy or radiotherapy for rectal cancer.
  6. No prior radiotherapy of the pelvis, for any reason.
  7. Presence of adequate contraception in fertile patients. Pregnant or breastfeeding women are excluded from participation.
  8. Ability to swallow tablets
  9. Written informed consent

Exclusion Criteria 

  1. Pregnant or breastfeeding women or fertile patients not using adequate contraception.
  2. Prior cytotoxic chemotherapy or radiotherapy for rectal cancer.
  3. Prior radiotherapy of the pelvis, for any reason.
  4. Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmia not well controlled with medication) or myocardial infarction within the last 12 months.
  5. Pre-existing condition which would deter chemoradiotherapy or radiotherapy, i.e. fistulas, severe ulcerative colitis (particularly patients currently taking Sulphasalazine), Crohn’s disease, prior adhesions.
  6. History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant precluding informed consent or interfering with compliance for oral drug intake.

More Information

Visit ANZTCR for more detailed information on inclusion/exclusion criteria and eligibility.

Funding

Cancer Australia

Trial Status

Completed

Cancer Type

Colorectal Cancer

Protocol Title

Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer.

Publication Reference

Gormly KL, Coscia C, Wells T, Tebbutt N, Harvey JA, Wilson K, Schmoll HJ, Price T. MRI rectal cancer in Australia and New Zealand: an audit from the PETACC-6 trial. Journal of Medical Imaging and Radiation Oncology 2016; 60(5): 607–615.

Conference Presentation Reference

  1. Price T, Martyn J, Gill R, Hruby G, Gormly K, Harvey J, Ng S, Tebbutt N. PETACC-6: preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin vs. capecitabine alone in locally advanced rectal cancer. Clinical Oncological Society of Australia (COSA) Annual Scientific Meeting; 9–11 Nov 2010; Melbourne. Asia-Pacific Journal of Clinical Oncology 2010; 6(suppl 3): 180. Abstract 284.
  2. Schmoll H, Haustermanns K, Price TJ, Nordlinger B, Hofheinz R, Daisne J, Janssens JF, Brenner B, Schmidt P, Reinel H, Hollerbach S, Caca K, Fauth FW, Hannig CV, Zalcberg J, Tebbutt NC, Mauer M, Messina CG, Lutz M, Van Cutsem E. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine ±oxaliplatin in locally advanced rectal cancer: interim analysis for disease-free survival of PETACC 6. European Society for Medical Oncology Congress; 26–30 Sep 2014; Madrid.
  3. Schmoll HJ, Haustermans K, Price TJ, Nordlinger B, Hofheinz R, Daisne JF, Janssens J, Brenner B, Schmidt P, Reinel H, Hollerbach S, Caca K, Fauth FWB, Hannig C, Zalcberg JR, Tebbutt NC, Mauer ME, Messina CGM, Lutz MP, Van Cutsem E. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: disease-free survival results at interim analysis. American Society of Clinical Oncology 50th Annual Meeting; 30 May–3 Jun 2014; Chicago.
  4. Schmoll H, Haustermans K, Price T, Nordlinger B, Hofheinz R, Daisne J, Janssens J, Brenner B, Schmidt P, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig C, Zalcberg J, Tebbutt N, Mauer M, Messina C, Lutz M, Van Cutsem E, for the EORTC GITCG A, AGITG, EORTC ROG, BGDO, FFCD,. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: First results of the PETACC-6 randomized phase III trial. American Society of Clinical Oncology Annual Meeting; 31 May–4 Jun 2013; Chicago. Journal of Clinical Oncology; 31 (suppl.): 3531.
  5. Schmoll HJ, Price T, Haustermanns K, Nordlinger B, Hofheinz RD, Daisne JF, Janssens J, Schmidt P, Reinel H, van Cutsem E, EORTC GITCG, AIO, AGITG, EORTC ROG, BGDO, FFCD. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin vs. capecitabine alone in locally advanced rectal cancer: response to the local treatment after chemoradiation and surgery as secondary endpoint. Deutsche, Österreichische und Schweizerische Gesellschaften für Hämatologie und Onkologie; 18–22 Oct 2013; Vienna.

Aim

PETACC-6 aims to investigate if addition of oxaliplatin to pre-operative capecitabine chemoradiotherapy and post-operative capecitabine chemotherapy improves disease free survival in patients with locally advanced rectal cancer.

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

PETACC-6 is part of an international study led by the European Organisation for the Research and Treatment of Cancer. The aim of the trial is to test whether adding the new chemotherapy drug oxaliplatin to pre-operative chemo-radiotherapy and post-operative chemotherapy can reduce the risk of recurrence or death for patients with locally advanced rectal 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 terms of complete response and disease free survival rates for stage III colorectal cancer. Capecitabine, however, offers reduced toxicity. The addition of oxaliplatin to capecitabine has shown to be effective and safe in phase II trials of preoperative chemoradiotherapy and in large phase III trials for stage II/III colorectal cancer.

The study is currently in the follow up stage. Analysis of data was undertaken early in 2016 and five-year follow up data has been collected until mid-June 2017 when final analysis will be undertaken.

Clinical Trial Design

The PETACC-6 study is an open-label, randomised, multi-national, two-arm phase III study. Eligible patients were randomised to one of two treatment groups.

Participants in the control group received the chemotherapy drug capecitabine with radiotherapy before surgery, followed by capecitabine after surgery. Participants in the investigational arm received capecitabine with oxaliplatin and radiotherapy before surgery, followed by capecitabine and oxaliplatin after surgery.

All participants in this trial are being followed for 5 years post treatment.

Contact Email

petacc6@ctc.usyd.edu.au

Principal Investigator

Professor Tim Price (Queen Elizabeth Hospital, Woodville SA)

More Information

Visit ANZTCR for more detailed information on inclusion/exclusion criteria and eligibility.

Funding

Cancer Australia