Condition category
Cancer
Date applied
17/09/2009
Date assigned
13/11/2009
Last edited
11/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Paul Symonds

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01229930

Protocol/serial number

C-2009-01

Study information

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

Acronym

CIRCCa (Cediranib In Recurrent Cervical Cancer)

Study hypothesis

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

Leicestershire, Northamptonshire & Rutland Research Ethics Committee 1, 07/01/2010, ref: 09/H0406/120

Study design

Late phase II randomised placebo-controlled trial

Primary study design

Interventional

Secondary study design

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

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 names

Cediranib, carboplatin, paclitaxel

Primary outcome measures

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.

Secondary outcome measures

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.

Overall trial start date

01/01/2010

Overall trial end date

31/12/2012

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

130

Participant 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

Recruitment start date

02/06/2010

Recruitment end date

31/07/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Leicester
Leicester
LE19 4LF
United Kingdom

Sponsor information

Organisation

NHS Greater Glasgow and Clyde (UK)

Sponsor details

Research and Development Central Office
The Tennent Institute
1st Floor
Wester Infirmary
38 Church Street
Glasgow
G11 6NT
United Kingdom

Sponsor type

Government

Website

http://www.nhsggc.org.uk

Organisation

University of Glasgow (UK)

Sponsor details

Research and Enterprise
10 The Square
Glasgow
G12 8QQ
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK (CRUK) (UK) (ref: CRUK/10/001)

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Funder name

Educational Grant from Astra Zeneca (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

2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/26474517

Publication citations

Additional files

Editorial Notes

11/03/2016: Publication reference added.