TroVax® and cyclophosphamide treatment in colorectal cancer

ISRCTN	ISRCTN54669986
DOI	https://doi.org/10.1186/ISRCTN54669986
Protocol serial number	SPON868-10
Sponsor	Cardiff University (UK)
Funder	Cancer Research Wales

Submission date: 10/12/2010
Registration date: 05/04/2011
Last edited: 25/10/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-vaccine-trovax-after-treatment-for-bowel-cancer-that-has-spread-tacticc

Contact information

Dr Andrew Godkin
Scientific

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

Study information

Primary study design	Interventional
Study design	Interventional multicentre randomised 2 x 2 factorial design pilot study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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 acronym	TaCTiCC
Study objectives	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(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Colorectal cancer
Intervention	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	Drug
Phase	Phase I/II
Drug / device / biological / vaccine name(s)	TroVax®
Primary outcome measure(s)	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
Key secondary outcome measure(s)	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
Completion date	23/06/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	54
Total final enrolment	52
Key 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
Key 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
Date of first enrolment	01/04/2011
Date of final enrolment	31/03/2014

Locations

Countries of recruitment

United Kingdom
Wales

Study participating centre

Henry Wellcome Building

Cardiff
CF14 4XN
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	12/10/2017		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results			25/10/2022	No	Yes

Editorial Notes

25/10/2022: Cancer Research UK plain English results link and total final enrolment added.
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.