Clinical trial NCT01566240: Induction Chemotherapy Plus Chemoradiation as First Line Treatment for Locally Advanced Cervical Cancer
Official title: A Phase III Multicentre Trial of Weekly Induction Chemotherapy Followed by Standard Chemoradiation Versus Standard Chemoradiation Alone in Patients With Locally Advanced Cervical Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Cervical Cancer
Keywords: Cervical Cancer
Chemotherapy
Paclitaxel
Carboplatin
Cisplatin
Radiotherapy
Chemoradiation
Brachytherapy
Stage IB2 Cervical Cancer
Stage IIA Cervical Cancer
Stage IIB Cervical Cancer
Stage IIIB Cervical Cancer
Stage IVA Cervical Cancer
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
First posted: 2012-03-29
Enrollment: 500
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Overall Survival
timeFrame: 5 years
Secondary outcomes:
measure: Progression free survival
timeFrame: 12 weeks post treatment and then as required
measure: Adverse events (AE) as assessed by the Common Terminology Criteria for Adverse Events v4.03
timeFrame: To be assessed at every timepoint i.e. baseline; at every chemotherapy cycle, at all follow up visits.
measure: Quality of Life (UK and Ireland only) as assessed by EORTC QLQ-C30, QLQ-CX24 and EQ-5D
timeFrame: 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)
measure: Patterns of first relapse (local and/or systemic)
timeFrame: 12 weeks post treatment and as required
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Instituto do Câncer do Estado de São Paulo
city: Kolkata
country: India
facility: Chittaranjan National Cancer Institute (CNCI)
city: Kolkata
country: India
facility: Saroj Gupta Cancer Centre and Research Institute
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
state: Lombardy
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerologia (INCAN)
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
state: Devon
city: London
country: United Kingdom
facility: University College London Hospital
state: Greater London
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
state: South Yorkshire
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Boston
country: United Kingdom
facility: Pilgrim Hospital
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Foundation Trust
city: Glasgow
country: United Kingdom
facility: Beatson WOSCC
city: Gloucester
country: United Kingdom
facility: Gloucester Royal Hospital
city: Grantham
country: United Kingdom
facility: Grantham and District Hospital
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: St Bart's Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Stoke-On-Trent
country: United Kingdom
facility: Royal Stoke University Hospital
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: University College London Hospitals
name: Mary Dr McCormack, MBBS, FRCR
role: PRINCIPAL_INVESTIGATOR
References: