The Overall Aim of the Trial is to Investigate Whether the Addition of Weekly Chemotherapy Improves Overall Survival Compared With Chemoradiation Alone in Patients With Locally Advanced Cervical Cancer (INTERLACE)

Inclusion Criteria:

• Histologically confirmed FIGO stage Ib2-IVa squamous, adeno or adenosquamous carcinoma of the cervix (except FIGO IIIA)
• 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)
• Capable of providing written or witnessed informed consent

Patients with positive 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*
• Involvement of lower 1/3 vagina (FIGO IIIA disease)
• 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
• Documented positive HIV antibody test or HIV viral load (patients recruited from high risk countries or who have moved within the past 10 years from high risk countries)
• Active TB
• 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