Induction Chemotherapy Plus Chemoradiation as First Line Treatment for Locally Advanced Cervical Cancer
INTERLACE
A Phase III Multicentre Trial of Weekly Induction Chemotherapy Followed by Standard Chemoradiation Versus Standard Chemoradiation Alone in Patients With Locally Advanced Cervical Cancer
3 other identifiers
interventional
500
5 countries
35
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Nov 2012
Longer than P75 for phase_3
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 27, 2012
CompletedFirst Posted
Study publicly available on registry
March 29, 2012
CompletedStudy Start
First participant enrolled
November 8, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2026
ExpectedDecember 5, 2024
December 1, 2024
13.2 years
March 27, 2012
December 4, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival
5 years
Secondary Outcomes (4)
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.
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)
Patterns of first relapse (local and/or systemic)
12 weeks post treatment and as required
Study Arms (2)
Chemoradiation
ACTIVE COMPARATORRadiotherapy (external beam and brachytherapy) plus concurrent Cisplatin weekly for 5 weeks
Induction Chemotherapy + Chemoradiation
EXPERIMENTAL6 cycles of weekly Paclitaxel and Carboplatin followed by Chemoradiation as per Active Comparator
Interventions
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 AUC 2 (capped at 270mg maximum total dose) weekly for 6 weeks i.e. on day 1, 8, 15, 22, 29, \& 36.
Radiotherapy comprising external beam 40-50.4Gy in 20-28 fractions plus intracavity brachytherapy to achieve a minimum total EQD2 dose of 78-86Gy.
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.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University College, Londonlead
- Cancer Research UKcollaborator
Study Sites (35)
Instituto do CĂ¢ncer do Estado de SĂ£o Paulo
SĂ£o Paulo, 01246-000, Brazil
Chittaranjan National Cancer Institute (CNCI)
Kolkata, India
Saroj Gupta Cancer Centre and Research Institute
Kolkata, India
Istituto Europeo di Oncologia
Milan, Lombardy, 20141, Italy
Instituto Nacional de Cancerologia (INCAN)
Mexico City, Mexico
North Devon District Hospital
Barnstaple, Devon, EX31 4JB, United Kingdom
University College London Hospital
London, Greater London, NW1 2BU, United Kingdom
Weston Park Hospital
Sheffield, South Yorkshire, S10 2SJ, 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, EX2 5DY, 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
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
The Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, 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, NG5 1PB, 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
Related Publications (1)
McCormack M, Eminowicz G, Gallardo D, Diez P, Farrelly L, Kent C, Hudson E, Panades M, Mathew T, Anand A, Persic M, Forrest J, Bhana R, Reed N, Drake A, Adusumalli M, Mukhopadhyay A, King M, Whitmarsh K, McGrane J, Colombo N, Mak C, Mandal R, Chowdhury RR, Alamilla-Garcia G, Chavez-Blanco A, Stobart H, Feeney A, Vaja S, Hacker AM, Hackshaw A, Ledermann JA; INTERLACE investigators. Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial. Lancet. 2024 Oct 19;404(10462):1525-1535. doi: 10.1016/S0140-6736(24)01438-7. Epub 2024 Oct 14.
PMID: 39419054DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Mary Dr McCormack, MBBS, FRCR
University College London Hospitals
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 27, 2012
First Posted
March 29, 2012
Study Start
November 8, 2012
Primary Completion
February 1, 2026
Study Completion (Estimated)
December 1, 2026
Last Updated
December 5, 2024
Record last verified: 2024-12