Condition category
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Contact information



Primary contact

Dr Andrew Godkin


Contact details

Henry Wellcome Building
School of Medicine
Heath Park
CF14 4XN
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

A pilot study to assess the effect of regulatory T cell depletion on 5T4-containing MVA (TROVAX®) vaccination in patients with INOPERABLE metastatic colorectal cancer



Study hypothesis

This study will assess the efficacy of using either cyclophosphamide, or a pox virus based vaccine containing the tumour antigen 5T4 called TroVax® (Oxford BioMedica), or both, to deplete T-regs and enhance an immune response following completion of an initial 12 weeks of palliative chemotherapy. Patients who have inoperable metastatic disease will be recruited.

Ethics approval

Not provided at time of registration

Study design

Interventional multicentre randomised 2 x 2 factorial design pilot study

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet


Colorectal cancer


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 doses)
3. Group 3: Vaccination (i.m.) TroVax® (1 x 109 TCID50/mL) at week 1, 3, 5, 7, 9 and 13
4. Group 4: Metronomic cyclophosphamide 50 mg bd (oral) on weeks 1 (14 doses) and week 3 (12 doses), followed by i.m. TroVax® (1 x 109 TCID50/mL) on weeks 4, 6, 8, 10, 12 and 16

Intervention type



Phase I/II

Drug names


Primary outcome measure

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 outcome measures

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

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant 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

Participant type


Age group




Target number of participants


Participant 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

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Henry Wellcome Building
CF14 4XN
United Kingdom

Sponsor information


Cardiff University (UK)

Sponsor details

Research and Commercial Division
7th floor
30-36 Newport Road
CF24 0DE
United Kingdom

Sponsor type




Funder type


Funder name

Cancer Research Wales

Alternative name(s)

Ymchwil Canser Cymru, CRW

Funding Body Type

private sector organisation

Funding Body Subtype

Other non-profit organizations


United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2017 results in:

Publication citations

Additional files

Editorial Notes

24/07/2019: The overall trial end date has been changed from 31/03/2014 to 23/06/2016. 12/09/2017: Publication reference added.