Weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer

ISRCTN	ISRCTN98873899
DOI	https://doi.org/10.1186/ISRCTN98873899
EudraCT/CTIS number	2005-000134-20
ClinicalTrials.gov number	NCT00462397
Secondary identifying numbers	1517

Submission date: 29/04/2010
Registration date: 29/04/2010
Last edited: 10/09/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-at-chemotherapy-followed-by-chemotherapy-and-radiotherapy-together-for-locally-advanced-cervical-cancer

Contact information

Ms Mandy Feeney
Scientific

Cancer Research UK and UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom

Study information

Study design	Non-randomised interventional treatment trial
Primary study design	Interventional
Secondary study design	Non randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Phase II non-randomised interventional treatment study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer
Study acronym	CxII
Study objectives	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(s)	Cambridgeshire 1 Research Ethics Committee approved on the 17/05/2005 (ref: 04/Q0104/163)
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	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 study start date	14/06/2005
Completion date	28/11/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target number of participants	Planned Sample Size: 50; UK Sample Size: 50
Key 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
Key exclusion criteria	1. Pregnant or breast feeding patients 2. Previous diagnosis of cancer, except basal cell carcinoma (BCC) skin 3. Active cardiac disease
Date of first enrolment	14/06/2005
Date of final enrolment	28/11/2008

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Cancer Research UK and UCL Cancer Trials Centre

London
W1T 4TJ
United Kingdom

Sponsor information

University College London (UK)
University/education

Gower Street
London
WC1E 6BT
England
United Kingdom

Website	http://www.ucl.ac.uk
"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Government

University College London Hospitals NHS Foundation Trust (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results				No	Yes
Results article	results	25/06/2013		Yes	No

Editorial Notes

10/09/2019: ClinicalTrials.gov number added.
19/10/2018: Cancer Research UK lay results summary link added to Results (plain English)
27/11/2015: Publication reference added.