Induction Chemotherapy Plus Chemoradiation as First Line Treatment for Locally Advanced Cervical Cancer

Cervical Cancer Clinical Trial

— INTERLACE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01566240
• Other study ID #: UCL 11/0034
• Secondary ID: 2011-001300-35C3
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 8, 2012
• Est. completion date: December 2026

Study information

• Verified date: June 2023
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: December 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Drug:
• Paclitaxel
Paclitaxel 80 mg/m2 (capped at 162mg maximum total dose) weekly for 6 weeks i.e. on days 1, 8, 15, 22, 29 & 36.
• Carboplatin
Carboplatin AUC 2 (capped at 270mg maximum total dose) weekly for 6 weeks i.e. on day 1, 8, 15, 22, 29, & 36.

Radiation:
• Radiotherapy
Radiotherapy comprising external beam 40-50.4Gy in 20-28 fractions plus intracavity brachytherapy to achieve a minimum total EQD2 dose of 78-86Gy.

Drug:
• Cisplatin
Cisplatin 40 mg/m2 (capped at 70mg total dose) weekly for five weeks maximum, commencing in the first week of radiotherapy or as soon as blood counts have recovered from induction chemotherapy.

Locations

Country	Name	City	State
Brazil	Instituto do Câncer do Estado de São Paulo	São Paulo
India	Chittaranjan National Cancer Institute (CNCI)	Kolkata
India	Saroj Gupta Cancer Centre and Research Institute	Kolkata
Italy	Istituto Europeo di Oncologia	Milan	Lombardy
Mexico	Instituto Nacional de Cancerologia (INCAN)	Mexico City
United Kingdom	North Devon District Hospital	Barnstaple	Devon
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Pilgrim Hospital	Boston
United Kingdom	Royal Sussex County Hospital	Brighton
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Cheltenham General Hospital	Cheltenham
United Kingdom	Royal Derby Hospital	Derby
United Kingdom	Royal Devon and Exeter NHS Foundation Trust	Exeter
United Kingdom	Beatson WOSCC	Glasgow
United Kingdom	Gloucester Royal Hospital	Gloucester
United Kingdom	Grantham and District Hospital	Grantham
United Kingdom	Castle Hill Hospital	Hull
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Lincoln County Hospital	Lincoln
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	St Bart's Hospital	London
United Kingdom	University College London Hospital	London	Greater London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	James Cook University Hospital	Middlesbrough
United Kingdom	Northampton General Hospital	Northampton
United Kingdom	Norfolk and Norwich University Hospital	Norwich
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Weston Park Hospital	Sheffield	South Yorkshire
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Royal Stoke University Hospital	Stoke-On-Trent
United Kingdom	Royal Cornwall Hospital	Truro
United Kingdom	The Clatterbridge Cancer Centre	Wirral
United Kingdom	New Cross Hospital	Wolverhampton

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	Cancer Research UK

Countries where clinical trial is conducted

Brazil,  India,  Italy,  Mexico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		5 years
Secondary	Progression free survival		12 weeks post treatment and then as required
Secondary	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.
Secondary	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)
Secondary	Patterns of first relapse (local and/or systemic)		12 weeks post treatment and as required