Colorectal cancer with resectable liver metastases MedDRA version: 14.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Oxaliplatin
Pharmaceutical Form: Powder for infusion
INN or Proposed INN: Oxaliplatin
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Product Name: Irinote
Sponsors
Southampton University Hospital NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Confirmed colorectal adenocarcinoma: o either previous or current histologically confirmed primary adenocarcinoma of colon or rectum, together with clinical or radiological evidence of advanced and / or metastatic disease. o or radiologically confirmed primary adenocarcinoma of colon or rectum, together with clinical or radiological evidence of advanced and / or metastatic disease. Histological evidence of primary colorectal cancer should be sought wherever possible but liver metastases should not be biopsied. • Presence of potentially resectable colorectal cancer liver metastases without detectable extra-hepatic tumour that cannot be completely resected. The consulting surgeon and the radiologist, according to local practice, will determine resectability (see appendix VI for guideline). The following patients are eligible: o Patients with rectal cancer who would be suitable for short course radiotherapy as an adjuvant treatment. o Patients who have had long course chemoradiation and R0 surgery for rectal cancer o Patients with metachronous metastases having undergone complete resection of the primary tumour without gross or microscopic evidence of residual disease (R0). o Patients with synchronous metastases who have undergone R0-resection of the primary tumour more than one month before randomisation. o Patients with synchronous metastases for whom there is sufficient evidence (for example by CT scan or diagnostic laparoscopy) that both the primary tumour and the liver metastases can be completely resected during the same procedure and that resection of primary cancer can be delayed for 3 to 4 months. o Unidimensionally measurable disease (RECIST criteria, see appendix V) to measure pre-operative response. o Patients with previously resected liver metastases for whom surgery was performed = 1 year previously. • No previous systemic chemotherapy for metastatic disease o adjuvant chemotherapy with 5FU +/- FA, capecitabine or oxaliplatin may have been given, if completed > 6 months prior to trial entry. o rectal chemoradiotherapy may have been given, if completed > 1 month prior to trial entry. • ECOG performance status =2. • Patients who are considered by responsible consultant to be fit to undergo combination chemotherapy and surgery. • Baseline laboratory tests (within 1 week prior to randomisation): o neutrophils = 1.5 x10 to the power of 9/l and platelet count = 100 x10 to the power of 9/l o serum bilirubin = 1.25 x upper limit of normal (ULN), alkaline phosphatase = 5 x ULN, and serum transaminase (either AST or ALT) = 2.5 x ULN o estimated creatinine clearance (Cockcroft; appendix VIII) >50ml/min or measured GFR (EDTA clearance) >50 ml/min. • All patients must be aged 18 years or older. • For women of childbearing potential, negative pregnancy test and adequate contraceptive precautions. Adequate contraception for men. • Written informed consent. • Consent to allow surplus pathological material to be analysed for translational research projects (patients may decline participation in this supplementary component and still participate in the main trial). Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: • Patients in whom there is an indication for chemotherapy to facilitate a R0 resection. • Patients in whom radio frequency ablation is felt to be an essential component of treatment. • Patients who are unfit for the chemotherapy regimens in this protocol or subsequent surgery, e.g.: o severe uncontrolled concurrent medical illness (including poorly-controlled angina or very recent MI, i.e. in previous 3 months) likely to interfere with protocol treatments. o Any psychiatric or neurological condition which is felt likely to compromise the patient's ability to give informed consent or to comply with oral medication. o Partial or complete bowel obstruction. o Pre-existing neuropathy (> grade 1). • Patients requiring ongoing treatment with a contraindicated concomitant medication. • Patients with another previous or current malignant disease which, in the judgement of the treating investigator, is likely to interfere with EPOC B treatment or assessment of response. • Patients with known hypersensitivity reactions to any of the components of the study treatments. • Patients with a second metastatic site. • Female patients who are pregnant or lactating. • Patients with a personal or family history suggestive of dihydropyrimidine dehydrogenase (DPD) deficiency or with known DPD deficiency. • Patients who are known to have tumours which are K-ras wild type. • Partial or complete bowel obstruction. • Chronic diarrhoea or inflammatory bowel disease. • Gilbert’s syndrome or other congenital abnormality of biliary transport (e.g. Crigler-Najjar syndrome, Dubin-Johnson syndrome). • Previous transplant surgery, requiring immunosuppressive therapy (due to interaction of cyclosporin-A with irinotecan). • Patients with = grade 1 residual neurotoxicity following oxaliplatin as adjuvant may be offered irinotecan and 5FU instead of oxaliplatin and fluoropyrimidine.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Currently some patients with colorectal cancer that has spread to the liver can be treated surgically and a significant number will effectively be cured. A prior study has shown that chemotherapy improves the survival of these patients if it is given both before and after the liver surgery. However this causes an increase in the complications of surgery. In this trial we are trying to find out if giving all the chemotherapy after surgery is possible, hence potentially avoiding this problem of complications. If this approach is feasible a larger trial will be undertaken to see if this approach is equivalent in terms of the long term survival of these patients.;Secondary Objective: We are interested to know whether patients will accept the chemotherapy to be given after the liver operation. We also want to know how much chemotherapy can actually be given, bearing in mind that a liver operation is a major procedure. We want to know how the quality of life in patients differs between the two approaches. As with all studies we will collect tissue from the removed liver and also from the patient’s blood to “bank” for future studies. Such studies may determine the suitability of different patients for different forms of treatment. These samples will be given a code so that they cannot be easily linked with the donor.;Primary end point(s): To determine whether it is feasible to recruit to a trial of peri-operative vs post operative chemotherapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): o The proportion of chemotherapy received. o Peri-operative surgical mortality (within 30 days of surgery). o Treatment related toxicity. o The effects of treatment on quality of life (QoL) - QoL data will be collected using EORTC QLQ-C30 (version 3), EORTC QLQ – LMC21, EuroQol Questionnaire (EQ-5D). o Overall survival (OS) for each treatment arm - OS will be determined by flagging and clinical review. o Length of stay. o Progression free survival. | — |
Countries
United Kingdom
Contacts
Public ContactE Dixon
University of Southampton Clinical Trials Unit
Outcome results
None listed