Locally advanced and/or metastatic colorectal cancer (mCRC) Cancer Malignant neoplasm of rectosigmoid junction
Conditions
Interventions
Patients will be recruited over 18 months. Participants randomised to the control arm will receive 12 cycles (q14 days) of FOLFIRI chemotherapy: irinotecan (180 mg/m^2) administered as a two hour infu
Sponsors
Cardiff University (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histological or cytological diagnosis of metastatic colorectal cancer 2. If patients progress within 6 months of adjuvant oxaliplatin containing chemotherapy they will be included in this study providing that they have no significant ongoing toxicity (excluding grade 1 neurotoxicity) 3. Measurable disease by Response Evaluation Criteria in Solid Tumours (RECIST v 1.1) 4. Adequate bone marrow, hepatic and renal function including the following: 4.1. Haemoglobin greater than or equal to 9.0 g/dl (no prior transfusion) or greater than or equal to 10.0 g/dl (transfusion within last 4 weeks), absolute neutrophil count greater than or equal to 1.5 x 10^9/L, platelets greater than or equal to 100 x 10^9/L 4.2. Total bilirubin less than 1.5 x upper normal limit 4.3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2.5 x upper normal limit (or less than or equal to 5 x UNL in the presence of liver metastases) 4.4. Creatinine less than or equal to 1.5 x upper normal limit 5. Aged greater than or equal to 16 years, either sex 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 7. Patients must have recovered from effects of major surgery 8. In view of concerns of possible teratogenicity, female patients must have no reproductive potential, i.e. must have a negative urine or serum pregnancy test within 7 days prior to start of trial, and must be post-menopausal 9. Males with reproductive potential should be prepared to use adequate contraception 10. Patient has provided written informed consent 11. Life expectancy of at least 12 weeks
Exclusion criteria
Exclusion criteria: 1. Any chemotherapy, radiotherapy (except for palliative reasons), endocrine therapy or immunotherapy within four weeks prior to trial entry. Patients may continue the use of corticosteroids provided the dose is stable for 4 weeks and not altered during the first 15 days of the study. 2. Have received more than one course of chemotherapy for metastatic disease, and any previous treatment with ZD4054 or irinotecan. Where oxaliplatin has been used in an intermittent schedule allowing patient holidays it will be considered equivalent to one prior line of therapy providing that patients have at least stable disease whilst on active treatment. 3. Extensive prior irradiation (likely to deplete bone marrow reserve) 4. Major surgery within 4 weeks of starting the study 5. Co-existing active infection or serious concurrent medical condition 6. Significant cardiovascular disease as defined by: 6.1. History of congestive heart failure requiring therapy 6.2. History of unstable angina pectoris or myocardial infarction up to 6 months prior to trial entry 6.3. Presence of severe valvular heart disease 6.4. Presence of a ventricular arrhythmia requiring treatment 7. Any co-existing medical condition that in the investigators judgement will substantially increase the risk associated with the patients participation in the study or potentially hamper compliance with the study protocol and follow-up schedule 8. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or compliance with the study protocol 9. Bone metastases 10. Known brain or leptomeningeal metastases unless patients have stable disease following surgical resection or radiosurgery of oligometastases 11. Gastrointestinal disorders likely to interfere with absorption of the study drug (e.g., partial bowel obstruction or malabsorption) 12. Patients known to be serologically positive for hepatitis B or hepatitis C (mandatory testing not required) 13. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) (mandatory testing not required) 14. Other previous or current malignant disease likely to interfere with protocol treatment or comparisons
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival (PFS) at 16 weeks from the date of enrolment. This is the proportion of participants who are alive at 16 weeks without disease progression according to RECIST v1.1. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. PFS (time-to-event). This is the proportion of participants who are alive at 16 weeks without disease progression according to RECIST v1.1. 2. Safety, tolerability (side effects) and feasibility of use (number of participants requiring dose delays or reductions and/or treatment withdrawal) 3. Objective response rate as assessed by RECIST v1.1 4. Overall survival (OS). Time from enrolment to death. Those still alive will be censored at time last seen. 5. To assess tumours for ETAR expression, K-ras status and alterations in relevant pathways such as MAPK/ERK and to potentially look at circulating tumour and lymphocyte cells in the blood | — |
Countries
United Kingdom
Outcome results
None listed