Colorectal cancer Cancer Colorectal cancer
Conditions
Interventions
1. Group 1: Control. No additional treatment unless clinically indicated.
2. Group 2: Metronomic cyclophosphamide 50mg bd (oral) as single agent on weeks 1 (14 doses) and on week 3 (12
Sponsors
Cardiff University (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient able to give informed consent personally or through a legal representative 2. Signed and dated written informed consent 3. Aged greater than or equal to 18 years, either sex 4. Clinical diagnosis of inoperable colorectal cancer 5. World Health Organization (WHO) performance status 0 - 2 6. Responding or stable disease as defined by oncologist following 12 weeks of chemotherapy as demonstrated on computed tomography (CT) scan in comparison with pre-treatment CT scan (Response Evaluation Criteria in Solid Tumours [RECIST]) 7. Subject is clinically immunocompetent 8. Any cancer related symptoms are under control with standard non-chemotherapy medications 9. Subject has adequate bone marrow function as defined by an absolute lymphocyte count greater than or equal to 500/µL, absolute neutrophil count greater than 1200/µL and platelet count greater than 100,000/µL
Exclusion criteria
Exclusion criteria: 1. Patient unable to give informed consent personally or through a legal representative 2. Creatinine level greater than 1.5 x upper limit of normal (ULN) 3. Bilirubin level greater than 50 µmol/l 4. Alkaline phosphatase greater than 3 x ULN 5. Aspartate aminotransferase (AST) and alanine aminotransferase ALT) greater than 2 x ULN 6. Prothrombin time greater than 18 seconds 7. Prior exposure to TroVax® 8. Life expectancy of less than 3 months 9. Diagnosed as being immunosupressed, receiving oral steroids (nasal sprays and inhalers are permitted) or receiving immunosuppressive therapy for oncology disorders, or following transplant 10. Patient has completed chemotherapy more than 2 weeks from the start of the treatment 11. Subject has clinically apparent/active autoimmune disease (prior confirmed diagnosis or treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave's disease, Hashimoto's thyroiditis, multiple sclerosis, insulin dependent diabetes mellitus and rheumatoid arthritis). Note: subjects with non-insulin dependent diabetes mellitus can be included, as can subjects with controlled and rarely flaring rheumatoid disease. 12. Subject has a platelet count prior to start of chemotherapy greater than 400,000/µL; monocytes greater than 80,000/ µL; haemoglobin less than 9 g/dL 13. Significant cancer related symptoms requiring immediate treatment with chemotherapy 14. "Currently active" second malignancy, other than non-melanoma skin cancer. Subjects are not considered to have a "currently active" malignancy if they have completed therapy more than 5 years previously and have no known evidence of residual or recurrent disease. 15. Evidence of significant clinical disorder or laboratory finding which in the opinion of the investigating physician makes it undesirable for the patient to participate in the trial. No participant should have a serious or uncontrolled intercurrent infection (including those positive for HIV). 16. Psychiatric illnesses/social situations that limit compliance with protocol requirements 17. Allergy to egg proteins, cyclophosphamide, neomycin or allergic response to vaccinia vaccines 18. Known cerebral metastases (known from previous investigations or clinically detectable) 19. Haemorrhagic cystitis 20. Severe infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Reduction in the frequency and/or function of Tregs measured in blood samples in patients treated with metronomic cyclophosphamide and/or TroVax® compared to patients not receiving cyclophosphamide 2. Development or increase in T cell responses in patients treated with cyclophosphamide and/or TroVax® versus untreated patients 3. Increase in anti-tumour immune responses measured in blood samples in patients treated with the vaccine TroVax® plus metronomic cyclophosphamide compared to TroVax® alone or no TroVax® group | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Overall Survival as the time in days from randomisation until death of any cause censoring at date of last follow up 2. Time To Progression with death as a competing risk will be measured as the time in days from randomisation until disease progression as determined by RECIST criteria for radiological imaging and clinical assessment 3. Progression Free Survival will be measured as the time in days from randomisation until progression or death of any cause censoring at date of last follow up | — |
Countries
United Kingdom, Wales
Outcome results
None listed