A Phase III Multicentre Trial of Weekly Induction Chemotherapy Followed by Standard Chemoradiation Versus Standard Chemoradiation Alone in Patients With Locally Advanced Cervical Cancer
Overview
- Phase
- Phase 3
- Intervention
- Radiotherapy
- Conditions
- Cervical Cancer
- Sponsor
- University College, London
- Enrollment
- 500
- Locations
- 35
- Primary Endpoint
- Overall Survival
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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.
Investigators
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
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
Arms & Interventions
Chemoradiation
Radiotherapy (external beam and brachytherapy) plus concurrent Cisplatin weekly for 5 weeks
Intervention: Radiotherapy
Chemoradiation
Radiotherapy (external beam and brachytherapy) plus concurrent Cisplatin weekly for 5 weeks
Intervention: Cisplatin
Induction Chemotherapy + Chemoradiation
6 cycles of weekly Paclitaxel and Carboplatin followed by Chemoradiation as per Active Comparator
Intervention: Paclitaxel
Induction Chemotherapy + Chemoradiation
6 cycles of weekly Paclitaxel and Carboplatin followed by Chemoradiation as per Active Comparator
Intervention: Carboplatin
Induction Chemotherapy + Chemoradiation
6 cycles of weekly Paclitaxel and Carboplatin followed by Chemoradiation as per Active Comparator
Intervention: Radiotherapy
Induction Chemotherapy + Chemoradiation
6 cycles of weekly Paclitaxel and Carboplatin followed by Chemoradiation as per Active Comparator
Intervention: Cisplatin
Outcomes
Primary Outcomes
Overall Survival
Time Frame: 5 years
Secondary Outcomes
- 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.)