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

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12608000403336
• Date of registration: 18/08/2008
• Prospective Registration: Yes
• Primary sponsor: Australasian Gastro-Intestinal Trials Group (AGITG)
• Public title: Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin vs. capecitabine alone in locally advanced rectal cancer
• Scientific title: Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin vs. capecitabine alone to establish disease-free survival outcomes in locally advanced rectal cancer (PETACC-6)
• Date of first enrolment: 27/05/2009
• Target sample size: 1090
• Recruitment status: Active, not recruiting
• URL: https://anzctr.org.au/ACTRN12608000403336.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Safety/efficacy;

Countries of recruitment

Australia, Belgium, France, Germany, Israel, New Zealand

Contacts

• Name: Ms PETACC-6 Trial Coordinator

• Name: Ms PETACC-6 Trial Coordinator

Key inclusion & exclusion criteria

Inclusion criteria: 1.Male or female patients with histologically proven adenocarcinoma of the rectum (tumour = 12 cm from the anal verge as assessed by rigid proctoscopy)
2.T3/4 or any node-positive disease
3.No evidence of metastatic disease
4.The disease must be considered either resectable at the time of entry or expected to become resectable after preoperative chemoradiation.
5.Age = 18 years.
6.World Health Organisation (WHO) / Eastern Cooperative Oncology Group (ECOG) Performance Status = 2
7.No prior cytotoxic chemotherapy or radiotherapy for rectal cancer.
8.No prior radiotherapy of the pelvis, for any reason.
9.Presence of adequate contraception in fertile patients. Pregnant or breastfeeding women are excluded from participation.
10.Adequate bone marrow, hepatic and renal function:
11.Haemoglobin = 10.0 g/dL, absolute neutrophil count = 1.5 x 109/L, platelet count = 100 x 109/L,
12. Alanine transaminase (ALAT)and aspartate transaminase (ASAT) = 2.5 x ULN
13.Alkaline phosphatase = 2.5 x ULN
14.Total bilirubin = 1.5 x ULN
15.Creatinine clearance > 50 mL/min
16.Creatinine = 1.5 x ULN
17.Ability to swallow tablets
18.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. Previous (within the last 5 years) or concurrent malignancies.
5.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.
6.Significant impairment of intestinal resorption (e.g. chronic diarrhoea, inflammatory bowel disease).
7.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.
8.Peripheral neuropathy = grade 2 (according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0).
9.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.

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Rectal cancer;Locally Advanced Rectal Cancer;
Rectal cancer
Locally Advanced Rectal Cancer

Cancer - Bowel - Back passage (rectum) or large bowel (colon)

Intervention(s)

Radiotherapy: 0.8 Gy per fraction given every week day for 5 weeks, total of 45 Gy in 25 fractions.
Capecitabine: (oral tablets) 1650mg/m2 daily on day 1-33 pre-operatively and 2000mg/m2 daily from day 1 to day 15 for 6 21-day cycles post-operatively
AND Oxaliplatin: (intravenously) 50mg/m2 on days 1, 8, 15, 22, and 29 pre-operatively and 130mg/m2 on day 1 for 6 21-day cycles post-operatively.

Primary Outcome(s)

Disease-free survival, defined as the time interval from randomisation to the first event of loco-regional failure, metastatic recurrence, the appearance of a secondary colorectal cancer or death.[During Treatment: 4-8 weeks after surgery and at the end of last cycle of chemotherapy; or as indicated if suspected progression. Follow-up: every 3 months for 3 years, then every 6 months for years 4-5, or as required if suspected progression.]

Secondary Outcome(s)

Distant failure. Measured via CT scan.[During Treatment: 4-8 weeks after surgery and at the end of last cycle of chemotherapy; or as indicated if suspected progression.
Follow-up: every 3 months for 3 years, then every 6 months for years 4-5, or as required if suspected progression.]

Histopathological R0 resection rate[At surgery]

Perioperative complication rate (e.g. infection, surgery-associated bleeding, renal failure, deep venous thromboembolism, etc.). Assessed through surgery reports and physical examination.[Within 30 days post surgery]

Toxicity. Assessed through physical examination and patient reports.[Weekly during chemoradiation treatment, within 1 week before surgery, 4-8 weeks post-surgery, before each cycle during post-operative chemotherapy and at the end of the last cycle of chemotherapy. During follow-up, every 3 months for the first 3 years, then every 6 months for years 4-5.]

Loco-regional failure. Measured via Computed tomography (CT) scan.[During Treatment: 4-8 weeks after surgery and at the end of last cycle of chemotherapy; or as indicated if suspected progression.
Follow-up: every 3 months for 3 years, then every 6 months for years 4-5, or as required if suspected progression.]

Sphincter preservation rate. Assessed through surgery reports and physical examination.[At baseline and surgery]

Overall survival[Every 3 months for 3 years then every 6 months thereafter. Patient followed-up for survival for a minimum of 5 years, however follow-up until death is desirable.]

Pathological downstaging rate, complete remission rate and tumor regression grade. Measured via CT scan.[Following pre-operative treatment, within 1 week prior to surgery.]

Secondary ID(s)

Nil

NCT00766155

Source(s) of Monetary Support

Cancer Australia

Secondary Sponsor(s)

European Organisation for Research and Treatment of Cancer (EORTC)

Ethics review

Status: Approved
Approval date:
Contact:

Cancer Institute NSW Clinical Research Ethics Committee

Status: Not approved
Approval date:
Contact:

SLHD Ethics Review Committee RPAH Zone