CIRCCa (Cediranib In Recurrent Cervical Cancer): a trial of carboplatin-paclitaxel plus cediranib versus carboplatin-paclitaxel plus placebo in metastatic/recurrent cervical cancer

ISRCTN	ISRCTN23516549
DOI	https://doi.org/10.1186/ISRCTN23516549
ClinicalTrials.gov (NCT)	NCT01229930
Protocol serial number	C-2009-01
Sponsors	NHS Greater Glasgow and Clyde, University of Glasgow (UK)
Funders	Cancer Research UK (CRUK) (UK) (ref: CRUK/10/001), Educational Grant from Astra Zeneca (UK)

Submission date: 17/09/2009
Registration date: 13/11/2009
Last edited: 29/03/2022

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://www.cancerhelp.org.uk/trials/a-trial-cediranib-advanced-cervical-cancer

Contact information

Dr Paul Symonds
Scientific

Reader in Oncology
Department of Cancer Studies and Molecular Medicine
University of Leicester
Level 2 - Osborne Building
Leicester Royal Infirmary
Leicester
LE19 4LF
United Kingdom

Phone	+44 (0)116 258 6294
Email	paul.symonds@uhl-tr.nhs.uk

Study information

Primary study design	Interventional
Study design	Late phase II randomised placebo-controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	CIRCCa (Cediranib In Recurrent Cervical Cancer): a randomised double-blind phase II trial of carboplatin-paclitaxel plus cediranib versus carboplatin-paclitaxel plus placebo in metastatic/recurrent cervical cancer
Study acronym	CIRCCa (Cediranib In Recurrent Cervical Cancer)
Study objectives	To provide preliminary evidence regarding whether the addition of cediranib to a combination of carboplatin and paclitaxel will increase progression free survival by 50% in patients with metastatic recurrent cervical carcinoma. On 01/03/2011 the overall trial end date was updated from 01/06/2011 to 31/12/2012.
Ethics approval(s)	Leicestershire, Northamptonshire & Rutland Research Ethics Committee 1, 07/01/2010, ref: 09/H0406/120
Health condition(s) or problem(s) studied	Cervical cancer
Intervention	The control arm (Arm A) is carboplatin AUC 5 and paclitaxel 175 mg/m^2 infused intravenously over 3 hours, repeated every 3 weeks for a maximum of 6 cycles, plus 20 mg placebo orally once daily. The trial arm (Arm B) is carboplatin AUC 5 and paclitaxel 175 mg/m^2 infused intravenously over 3 hours, repeated every 3 weeks for a maximum of 6 cycles, plus 20 mg cediranib orally once daily. Patients will be randomised in a double blind fashion to receive either Arm A or Arm B, and treatment with placebo or cediranib will be continued until patient progresses or toxicity becomes unacceptable. Neither the patient nor the Investigator will be aware of whether the patient's trial drug is cediranib or placebo tablets. Prior to progression patients will be followed up 2 monthly until end of year 2, every 6 months during years 3, 4 and 5 and yearly thereafter. After disease progression is documented, patients should be followed up 6-monthly during the first 5 years after randomisation and yearly thereafter.
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Cediranib, carboplatin, paclitaxel
Primary outcome measure(s)	Progression free survival Prior to progression patients will be followed up 2 monthly until end of year 2, every 6 months during years 3, 4 and 5 and yearly thereafter. After disease progression is documented, patients should be followed up 6 monthly during the first 5 years after randomisation and yearly thereafter. All primary and secondary outcomes will be assessed at all follow up visits until progression confirmed, after progression confirmed only applicable for overall survival to be assessed.
Key secondary outcome measure(s)	1. Overall survival 2. Response rate 3. Toxicity 4. Quality of life, assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires modules C30 and CX26 Prior to progression patients will be followed up 2 monthly until end of year 2, every 6 months during years 3, 4 and 5 and yearly thereafter. After disease progression is documented, patients should be followed up 6 monthly during the first 5 years after randomisation and yearly thereafter. All primary and secondary outcomes will be assessed at all follow up visits until progression confirmed, after progression confirmed only applicable for overall survival to be assessed.
Completion date	31/12/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target sample size at registration	130
Total final enrolment	69
Key inclusion criteria	1. Female and over 18 years of age 2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 3. Histologically proven carcinoma of the cervix (squamous, adenocarcinoma, adenosquamous mixed or small cell) 4. Either: 4.1. Persistent or relapsed inoperable disease after radical radiotherapy within the irradiated pelvis OR 4.2. Relapse after radical hysterectomy (after radical radiotherapy to pelvis if appropriate) OR 4.3. Extra pelvic metastases OR 4.4. Stage IVb disease at diagnosis 5. Patient not suitable for potentially curative surgical procedure 6. Measurable disease in at least one marker site 7. Adequate haematological function, as follows: 7.1. Haemoglobin greater than or equal to 10 g/dl 7.2. Neutrophils greater than or equal to 1.5 x 10^9/l 7.3. Platelets greater than or equal to 100 x 10^9/l 7.4. Calculated creatinine clearance greater than or equal to 35 ml/min (measured by EDTA) 8. Adequate biochemical function, as follows: 8.1. Bilirubin less than or equal to 1.5 x upper limit of normal (ULN) 8.2. Alanine amino-transferase (ALT) or aspartate amino-transferase (AST) less than or equal to 2.5 x ULN (or less than or equal to 5 x ULN if hepatic metastases) 9. Adequate coagulation as follows: 9.1.1. Prothrombin time ratio (PTR)/international normalised ratio (INR) less than or equal to 1.5 OR 9.1.2. PTR/INR between 2.0 and 3.0 for patients on stable doses of anticoagulants 9.2. Partial thromboplastin time less than 1.2 x control 10. Life expectancy greater than 12 weeks
Key exclusion criteria	1. They have received prior chemotherapy, except cisplatin administered along with radiotherapy as primary treatment 2. Relapse is confined to the pelvis after radical surgery in circumstance where radiotherapy or chemoradiotherapy would be appropriate 3. Relapse is potentially treatable with exenterative surgery 4. History of nervous or psychiatric disorder that would prevent informed consent and compliance 5. History of prior malignancy within the previous 5 years except for successfully treated basal cell skin cancer or in-situ breast cancer 6. Pregnant or lactating women 7. Fertile woman of childbearing potential not willing to use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) for the study duration and at least six months afterwards 8. Evidence of uncontrolled infection 9. Tumour involvement of bowel wall 10. History of pelvic fistulae 11. Sub-acute or acute intestinal obstruction 12. Major surgery within 28 days or anticipated while on study 13. Significant traumatic injury during 4 weeks preceding the potential first dose of cediranib 14. Non-healing wound, ulcer or bone fracture 15. Active bleeding 16. History or evidence of thrombotic or haemorrhagic disorders 17. History of inflammatory bowel disease 18. Proteinuria greater than 1+ on dipstick on two consecutive dipsticks taken no less than 1 week apart, unless urinary protein is less than 1.5 g in a 24-hour period 19. Significant cardiovascular disease (arterial thrombotic event within 12 months, uncontrolled hypertension or angina within 6 months, New York Heart Association (NYHA) grade 2 congestive cardiac failure, grade greater than or equal to 3 peripheral vascular disease or cardiac arrhythmia requiring medication). Patients with rate-controlled atrial fibrillation are eligible. 20. Prolonged QTc (corrected) interval of greater than 470 ms on electrocardiogram (ECG) or a family history of long QT syndrome 21. Central nervous system (CNS) disease (brain metastases, uncontrolled seizures or cerebrovascular accident/transient ischaemic attack/subarachnoid haemorrhage within 6 months) 22. History or clinical suspicion of spinal cord compression 23. Pre-existing sensory or motor neuropathy greater than or equal to grade 2 24. Known hypersensitivity to carboplatin or paclitaxel 25. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contra-indicates the use of an investigational drug or puts the patient at high risk for treatment-related complications
Date of first enrolment	02/06/2010
Date of final enrolment	31/07/2012

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

University of Leicester

Leicester
LE19 4LF
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/11/2015		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Plain English results		28/01/2016	29/03/2022	No	Yes

Editorial Notes

29/03/2022: The following changes have been made:
1. The Cancer Research UK lay results summary has been added.
2. The total final enrolment number has been added.
11/03/2016: Publication reference added.