None listed
Conditions
Brief summary
This study looks at whether receiving extra chemotherapy during a waiting period between radiotherapy and surgery can assist in shrinking a patient’s tumour even more when compared to just the waiting period alone and without any additional treatment. Who is it for? You are eligible for this study if you are 18 years and over, have a histologically proven adenocarcinoma, distal rectum (defined as being less than 12 cms from the anal verge on rigid sigmoidoscopy), and have non-metastatic (M0) disease. You may also be eligible if your health care professional recommends that you undergo long course preoperative chemoradiotherapy prior to surgery. More details on the eligibility criteria for this study can be found in the Inclusion Criteria field of this form. Trial Details Normally between radiotherapy and surgery there is a 6 week wait period to see if the tumour shrinks. Recent studies have suggested it may be beneficial to have chemotherapy in this period – although this experimental approach has only been tried in a small number of patients. The aim of this study is to see whether extra chemotherapy given in this wait period shrinks the tumour even more. The waiting period in this study will be 10 weeks. We will assess this at the time of surgery by clinical response (no tumour visible by eye) and by pathological response (no tumour visible under the microscope). We will also use the samples we take from the tumour to see whether we can identify any factors which might predict better outcomes for all patients with rectal cancer. If you choose to take part in this study, you will be randomised to either the standard preoperative chemoradiotherapy followed by a 10 week wait period without any additional chemotherapy (the SCRT group) OR the standard chemoradiotherapy followed by a 10 week wait period with additional chemotherapy (the XCRT group). Chemotherapy will be fluropyrimidine based using a standard regimen of infusional 5FU continuous throughout radiotherapy, at a dose of 225 mg/m2/day. A Picc line will be inserted prior to treatment and the infusional 5FU will be given through a Baxter infuser pump, in an ambulatory fashion, and will be changed once a week, for the duration of radiotherapy. A full blood count and MBA20 test will be performed weekly during chemoradiotherapy. For patients on the standard arm (the SCRT group), no further preoperative chemotherapy is planned. Patients on the investigational arm (XCRT group) will receive further chemotherapy as bolus 5FU (450 mg/m2 with leucovorin at 50mg/m2, on each of 3 days, 3 weekly for 3 cycles (week 9, 12, 15).
Interventions
This study will be a prospective randomised controlled trial comparing standard preoperative chemoradiotherapy followed by a wait period without chemotherapy (herein after called standard chemoradiotherapy (SCRT)) with standard chemoradiotherapy followed by a wait period with chemotherapy (hereinafter called extended chemoradiotherapy (XCRT)
Chemotherapy will be fluropyrimidine based using a standard regimen of infusional 5FU continuous throughout radiotherapy, at a dose of 225 mg/m2/day. A Pic
This study will be a prospective randomised controlled trial comparing standard preoperative chemoradiotherapy followed by a wait period without chemotherapy (herein after called standard chemoradiotherapy (SCRT)) with standard chemoradiotherapy followed by a wait period with chemotherapy (hereinafter called extended chemoradiotherapy (XCRT) Chemotherapy will be fluropyrimidine based using a standard regimen of infusional 5FU continuous throughout radiotherapy, at a dose of 225 mg/m2/day. A Picc line will be inserted prior to treatment and the infusional 5FU will be given through a Baxter infuser pump, in an ambulatory fashion, and will be changed once a week, for the duration of radiotherapy. Full blood count and MBA20 will be performed weekly during chemoradiotherapy. For patients on standard arm (SCRT), no further preoperative chemotherapy is planned. Patients on the investigational arm will receive further chemotherapy as bolus 5FU (450 mg/m2 with leucovorin at 50mg/m2, on each of 3 days, 3 weekly for 3 cycles (week 9, 12, 15). Fullblood count and MBA20 will be performed prior to each chemotherapy cycle. The wait period before surgery will be a standardised 10 weeks after completion of radiotherapy on both arms of the study
Sponsors
Royal Adelaide Hospital
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1.Histologically proven adenocarcinoma, distal rectum (defined as being less than 12 cms. from the anal verge on rigid sigmoidoscopy) 2.Non-metastatic (M0) disease as evidenced by CT chest and abdomen 3. Patients who following MDT discussion, are deemed to require long course preoperative chemoradiotherapy as appropriate neo-adjuvant therapy for their rectal cancer prior to surgical management (clinical stage T3/4 or any node positive disease). The nature of surgical management will be at the discretion of the surgeon responsible for their care. 4.WHO/ECOG Performance status <= 2 5.Adequate bone marrow, hepatic, and renal fuction Haemoglobin greater than or equal to10.0 g/dL (transfusions allowed to achieve or maintain levels) absolute neutrophil count greater than or equal to 1.5 x 10 9/L platelet count greater than or equal to 100 x 10 9/L ALAT greater than or equal to10 2.5 x ULN ASAT greater than or equal to10 2.5 x ULN Alkaline phosphatase greater than or equal to10 2.5 x ULN Total bilirubin greater than or equal to10 1.5 x ULN Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault) 6.Presence of adequate contraception in fertile patients
Exclusion criteria
Age – less than 18 or greater than 80 years 2. Inability to provide informed consent 3. Significant co-morbidities precluding the use of preoperative chemoradiotherapy, including the presence of clinically significant (i.e. active) cardiac disease 4. Known dihydropyrimidine dehydrogenase deficiency 5. Pregnant or breast feeding women
Outcome results
None listed