Condition category
Cancer
Date applied
29/04/2010
Date assigned
29/04/2010
Last edited
27/11/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Ms Mandy Feeney

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

2005-000134-20

ClinicalTrials.gov number

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 measures

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

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

http://www.ucl.ac.uk

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

Results - basic reporting

Publication summary

2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23695016

Publication citations

Additional files

Editorial Notes

27/11/2015: Publication reference added.