Induction Chemotherapy Plus Chemoradiation as First Line Treatment for Locally Advanced Cervical Cancer
- Conditions
- Cervical Cancer
- Interventions
- Registration Number
- NCT01566240
- Lead Sponsor
- University College, London
- Brief Summary
Chemoradiation has been the standard treatment for advanced cervical cancer for a decade, but one third of women still die from a failure to control systemic disease. In a recent multicentre phase II trial of 46 women the investigators found that, 68% of women had tumours that responded to weekly induction chemotherapy prior to chemoradiation. The induction chemotherapy had acceptable toxicity and did not compromise the standard chemoradiation treatment. In addition, the overall survival and progression free survival at 3 years was 66% (95% CI 4779). These results, together with acceptable toxicity, provide justification for evaluating induction chemotherapy prior to chemoradiation in a randomised phase III trial. The investigators aim to investigate in a randomised trial whether additional induction chemotherapy given on a weekly schedule immediately before standard chemoradiation leads to an improvement in overall survival. The investigators plan to recruit 770 women with locally advanced cervical cancer who are eligible for standard chemoradiation, they will be randomised to weekly carboplatin and paclitaxel chemotherapy for 6 weeks followed by chemoradiation or to chemoradiation alone. The trial will recruit for 4 years with 5 years of follow up period.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 500
- Histologically confirmed FIGO stage Ib2-IVa squamous, adeno or adenosquamous carcinoma of the cervix (except FIGO IIIA). Patients with histologically confirmed FIGO stage IB1 and positive lymph nodes are also eligible
- Deemed suitable and fit for radical chemoradiation
- Medically fit to receive carboplatin and paclitaxel
- ECOG performance status 0 - 1
- No evidence of active TB
- Aged 18 and over
- Adequate renal function, defined as a GFR ≥ 60 ml/min calculated using the Wright equation (or ≥ 50 ml/min for radioisotope GFR assessment)
- Adequate liver function, as defined by ALT or AST < 2.5 ULN and bilirubin < 1.25 ULN
- Adequate bone marrow function as defined by ANC ≥1.5 x 109/L, platelets ≥ 100 x 109/L
- Using adequate contraception precautions if relevant
- A documented negative HIV test (patients recruited from high risk countries or who have moved within the past 10 years from high risk countries)
- A documented negative pregnancy test (if applicable)
- Capable of providing written or witnessed informed consent
Patients with positive (pelvic/para-aortic/both) nodes (either histologically/PET positive ≥15 mm on CT/MRI) at or below the level of the aortic bifurcation may be included in the study provided none of the exclusion criteria apply.
- Previous pelvic malignancy (regardless of interval since diagnosis)
- Previous malignancy not affecting the pelvis (except basal cell carcinoma of the skin) where disease free interval is less than 10 years
- Positive lymph nodes (imaging or histological) above the aortic bifurcation*
- Hydronephrosis which has not undergone ureteric stenting or nephrostomy except where the affected kidney is non-functioning
- Evidence of distant metastasis i.e. any non-nodal metastasis beyond the pelvis
- Previous pelvic radiotherapy
- Prior diagnosis of Crohn's disease or Ulcerative colitis
- Uncontrolled cardiac disease (defined as cardiac function which would preclude hydration during cisplatin administration and any contraindication to paclitaxel)
- Pregnant or lactating * i.e. PET any size, CT/MRI ≥ 15mm
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Induction Chemotherapy + Chemoradiation Radiotherapy 6 cycles of weekly Paclitaxel and Carboplatin followed by Chemoradiation as per Active Comparator Chemoradiation Radiotherapy Radiotherapy (external beam and brachytherapy) plus concurrent Cisplatin weekly for 5 weeks Chemoradiation Cisplatin Radiotherapy (external beam and brachytherapy) plus concurrent Cisplatin weekly for 5 weeks Induction Chemotherapy + Chemoradiation Carboplatin 6 cycles of weekly Paclitaxel and Carboplatin followed by Chemoradiation as per Active Comparator Induction Chemotherapy + Chemoradiation Paclitaxel 6 cycles of weekly Paclitaxel and Carboplatin followed by Chemoradiation as per Active Comparator Induction Chemotherapy + Chemoradiation Cisplatin 6 cycles of weekly Paclitaxel and Carboplatin followed by Chemoradiation as per Active Comparator
- Primary Outcome Measures
Name Time Method Overall Survival 5 years
- Secondary Outcome Measures
Name Time Method Patterns of first relapse (local and/or systemic) 12 weeks post treatment and as required Quality of Life (UK and Ireland only) as assessed by EORTC QLQ-C30, QLQ-CX24 and EQ-5D Baseline, during induction chemotherapy (Week 4), day 1 of chemoradiation, during chemoradiation (Weeks 3), 4 weeks post end of treatment, and as part of follow up (3 monthly for 2 years; 6 monthly for 3 years until 5 years post randomisation) Progression free survival 12 weeks post treatment and then as required Adverse events (AE) as assessed by the Common Terminology Criteria for Adverse Events v4.03 To be assessed at every timepoint i.e. baseline; at every chemotherapy cycle, at all follow up visits.
Trial Locations
- Locations (35)
Royal Derby Hospital
🇬🇧Derby, United Kingdom
Pilgrim Hospital
🇬🇧Boston, United Kingdom
The Clatterbridge Cancer Centre
🇬🇧Wirral, United Kingdom
St Bart's Hospital
🇬🇧London, United Kingdom
Royal Devon and Exeter NHS Foundation Trust
🇬🇧Exeter, United Kingdom
Instituto do Câncer do Estado de São Paulo
🇧🇷São Paulo, Brazil
North Devon District Hospital
🇬🇧Barnstaple, Devon, United Kingdom
University College London Hospital
🇬🇧London, Greater London, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, South Yorkshire, United Kingdom
Belfast City Hospital
🇬🇧Belfast, United Kingdom
Royal Sussex County Hospital
🇬🇧Brighton, United Kingdom
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Cheltenham General Hospital
🇬🇧Cheltenham, United Kingdom
Beatson WOSCC
🇬🇧Glasgow, United Kingdom
Gloucester Royal Hospital
🇬🇧Gloucester, United Kingdom
Grantham and District Hospital
🇬🇧Grantham, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Lincoln County Hospital
🇬🇧Lincoln, United Kingdom
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
James Cook University Hospital
🇬🇧Middlesbrough, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Norfolk and Norwich University Hospital
🇬🇧Norwich, United Kingdom
Northampton General Hospital
🇬🇧Northampton, United Kingdom
Nottingham University Hospitals NHS Trust
🇬🇧Nottingham, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Royal Stoke University Hospital
🇬🇧Stoke-On-Trent, United Kingdom
Royal Cornwall Hospital
🇬🇧Truro, United Kingdom
New Cross Hospital
🇬🇧Wolverhampton, United Kingdom
Chittaranjan National Cancer Institute (CNCI)
🇮🇳Kolkata, India
Instituto Nacional de Cancerologia (INCAN)
🇲🇽Mexico City, Mexico
Saroj Gupta Cancer Centre and Research Institute
🇮🇳Kolkata, India
Istituto Europeo di Oncologia
🇮🇹Milan, Lombardy, Italy
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom
Castle Hill Hospital
🇬🇧Hull, United Kingdom