Additional identifiers
EudraCT number
2010-023195-22
ClinicalTrials.gov number
Protocol/serial number
10000
Study information
Scientific title
Randomised controlled open-label trial of TPF (taxane cisplatin 5-fluorouracil) induction chemotherapy in the surgical management of locally advanced head and neck cancer
Acronym
TITAN
Study hypothesis
This is a trial of treatment intensification in a high-risk population of potentially curable patients. Induction chemotherapy is a significant recent advance in the management of locally advanced squamous cell carcinoma of the head and neck (SCCHN), although its use in combination with surgery and postoperative radiotherapy (PORT) is under-researched. Induction chemotherapy (ICT) offers the potential for better delivery of drugs to "treatment naïve" tumours with an intact blood supply and, at the same time, provides maximal treatment to eradicate micro-metastasis, with the prospect of both better local and local systemic control of disease.
Thus the rationale is to study the effects of intensification of treatment using induction TPF in locally advanced SCCHN in those anatomical sites treated by primary surgery.
Ethics approval
First MREC, 11/04/2011, ref: 11/NW/0149
Study design
Randomised, interventional
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not provided at time of registration
Condition
Head and neck cancer
Intervention
Patients will be randomised in a 1:1 ratio across 2 arms
Arm A: surgery and post operative conformal radiation therapy (CRT) (PO(C)RT)
Conventional treatment for the stage and site of disease is performed as per the original (pre-randomisation) imaging, examination under anaesthetic and clinical findings.
Arm B: Induction Chemotherapy
Patients will recieve 3 cycles of induction chemotherapy at 21 days intervals, prior to recieving surgery and PO(C)RT
To be followed up at 60 month(s)
Intervention type
Drug
Phase
Phase II/III
Drug names
Taxane, cisplatin, 5-fluorouracil
Primary outcome measure
Feasibility of recruitment into the TITAN trial (specifically the number of participants)
Secondary outcome measures
1. Randomisation: screening ratio
2. The percentage of patients in the TPF arm who complete the full course of treatment
Overall trial start date
01/09/2011
Overall trial end date
01/09/2011
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Age >18 years
2. Histopathological diagnosis of head and neck squamous cell carcinoma
3. Tumour (T) stage in one of the following site categories:
3.1. Lip/ Oral cavity: stage T3 or T4a (and >=4cm in largest dimension)
3.2. Paranasal /nasal: stage T4a
3.3. Larynx: stage T4a
3.4. Hypopharynx: stage T3 or T4a
3.5. Cervical oesophagus: stage T3 or T4a
3.6. Oropharynx: stage T3 or T4a and HPV-ve
4. Any lymph node (N) stage
5. No metastases (M0)
6. An multidisciplinary team (MDT) decision to offer surgery as primary modality of treatment
7. World Health Organisation (WHO) performance status 0 or 1
8. Resectable by conventional criteria in both primary site and any cervical lymph node involvement
9. Male or female paticipants
10. Lower age limit: 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
UK Sample Size: 50
Participant exclusion criteria
1. Those tumours staged to T4a on the basis of early mandibular invasion alone, i.e. <4cm in the maximum dimension
2. Unresectable disease on clinical staging (including imaging) of primary tumour or cervical metastasis
3. Distant metastases (note: positron emission tomography - computed tomography [PET-CT] is necessary investigation for all patients entering trial - as such additional CT chest will usually not be required to exclude pulmonary or hepatic metastases)
4. Nasopharynx site
5. Human papillomavirus (HPV) - positive oropharyngeal cancer (OPC)
6. Pregnancy or lactation
7. Patients with haemoglobin of <10g/dl
8. Patients with neutrophil counts of <1.5 x 109/l.
9. Patients with thrombocyte counts of <100 x 109/l.
10. Patients with significant hepatic impairment (Bilirubin >1.5x upper limit of normal range; ALT >2.5x upper limit of normal range; ALP >5x upper limit of normal range)
11. Patients with significant renal impairment (For the purpose of the study, significant renal impairment is classed as GFR <50ml/min>. However, sites may use their local policy if a higher threshold is dictated.)
12. Patients who lack mental capacity to give informed consent
13. Patients whose co morbidities or concomitant medications otherwise preclude TPF chemotherapy
14. All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be a condom
Recruitment start date
01/09/2011
Recruitment end date
01/09/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Liverpool Cancer Research Centre
Liverpool
L3 9TA
United Kingdom
Sponsor information
Organisation
Aintree University Hospitals NHS Foundation Trust (UK)
Sponsor details
Aintree University Hospitals
Fazakerley Hospital
Lower Lane
Liverpool
L9 7AL
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
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