Additional identifiers
EudraCT number
2005-000134-20
ClinicalTrials.gov number
NCT00462397
Protocol/serial number
1517
Study information
Scientific title
Phase II non-randomised interventional treatment study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer
Acronym
CxII
Study hypothesis
For the past 10 years cisplatin-based chemoradiation (CRT) has been the treatment of choice for all patients with locally advanced cervical cancer. The key CRT trials showed a reduction in the risk of death by 30 - 50% with an absolute improvement in 5 year survival of 12%. However, a large proportion of patients in these trials had early stage disease (stage I, II) so the results may not be broadly applicable to women with more advanced disease/large tumours, or positive nodes. The outlook for such patients remains poor and new approaches are needed.
To date, trials addressing the role of neoadjuvant chemotherapy (NACT) have generated conflicting data. Although a meta-analysis of 21 randomised trials failed to show any overall improvement in survival with NACT, an association between outcome and cycle length has been observed. Trials with a cycle length of 14 days or less were associated with an improvement in survival of approximately 7% at 5 years, while longer cycle lengths had a detrimental effect on outcome.
Therefore, it is postulated that a short course of dose dense NACT with weekly cycles of treatment prior to definitive CRT might downstage the tumours, lengthen the exposure to systemic treatment and improve outcome. Several cytotoxic agents have shown activity in cervical cancer, however very few of these agents have been tested in the weekly setting. This phase II study will assess the use of neoadjuvant weekly paclitaxel and carboplatin chemotherapy followed by concomitant chemoradiation in 50 patients with locally advanced cervical cancer.
Ethics approval
Cambridgeshire 1 Research Ethics Committee approved on the 17/05/2005 (ref: 04/Q0104/163)
Study design
Non-randomised interventional treatment trial
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Gynaecological Cancer; Disease: Cervix
Intervention
Neoadjuvant chemotherapy:
Weekly treatment for six weeks: paclitaxel (80 mg/m^2 IV) followed by carboplatin AUC2 IV on days 1, 8, 15, 22, 29 and 36.
Chemoradiation:
Cisplatin: 40 mg/m^2 (maximum 70 mg) weekly for 6 weeks maximum, commencing in week 7 of treatment regimen (or as soon as blood counts have recovered).
Pelvic radiotherapy: 50.4 Gy in 28# over 5.5 weeks
High dose rate brachytherapy: 14 Gy in 2# (1 or 2 intracavitary insertions)
Pelvic sidewall boost (unilateral or bilateral) for all patients FIGO stage IIb and above with parametrial/pelvic sidewall disease extension, 5.4 Gy in 3# over 3 days.
Patient follow-up after treatment: 3 monthly for 2 years
Study entry: registration only
Intervention type
Drug
Phase
Phase II
Drug names
Cisplatin
Primary outcome measure
Overall response to both the neoadjuvant combination chemotherapy and the concomitant chemoradiotherapy. 6 week assessment after neoadjuvant chemotherapy by clinical examination and MRI pelvis according to RECIST; 12 week assessment after concomitant chemoradiotherapy by clinical examination, MRI pelvis and CT abdomen by RECIST.
Secondary outcome measures
1. Response rate to neoadjuvant chemotherapy
2. The toxicity of neoadjuvant weekly paclitaxel and carboplatin chemotherapy, as defined by Common Toxicity Criteria (CTC)
3. Overall survival
4. Progression free survival
Patients will be followed 3 monthly for two years, patients will be evaluated clinically and toxicity assessed.
Overall trial start date
14/06/2005
Overall trial end date
28/11/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Histologically confirmed and reviewed at the cancer centre International Federation of Gynaecology and Obstetrics (FIGO) stage Ib2 - IVa squamous, adeno-, or adenosquamous carcinoma of the cervix suitable for radical chemoradiation
2. EUA, cystoscopy and sigmoidoscopy performed by Gynaecological Oncologist +/- Clinical Oncologist to confirm FIGO stage with biopsy of any suspicious lesions in bladder, vagina or rectum
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
4. Age over 18, no upper limit, providing patient deemed fit by supervising oncologist to receive chemoradiation
5. Adequate renal function, as defined by glomerular filtration rate (GFR) estimated by EDTA or creatinine clearance (24 hour urine) greater than or equal to 60 ml/min
6. Adequate liver function, as defined by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 2.5 upper limit of normal (ULN), and bilirubin less than 1.25 ULN
7. Adequate bone marrow function, as defined by white cell count (WCC) greater than 3.0 x 10^9/litre, neutrophils greater than 1.5 x 10^9/litre, and platelets greater than 100 x 10^9/litre
8. Placement of ureteric stents in all patients with hydronephrosis regardless of renal function
9. Normal electrocardiogram (ECG)
10. Written informed consent
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
Planned Sample Size: 50; UK Sample Size: 50
Participant exclusion criteria
1. Pregnant or breast feeding patients
2. Previous diagnosis of cancer, except basal cell carcinoma (BCC) skin
3. Active cardiac disease
Recruitment start date
14/06/2005
Recruitment end date
28/11/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Cancer Research UK and UCL Cancer Trials Centre
London
W1T 4TJ
United Kingdom
Sponsor information
Organisation
University College London (UK)
Sponsor details
Gower Street
London
WC1E 6BT
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
University College London Hospitals NHS Foundation Trust (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23695016