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Clinical Trial Results:
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

Summary
EudraCT number	2009-011542-25
Trial protocol	GB
Global end of trial date	30 Apr 2015

Results information
Results version number	v1(current)
This version publication date	11 May 2016
First version publication date	11 May 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

C-2009-01

ISRCTN number

ISRCTN23516549

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

NHS Greater Glasgow and Clyde

Sponsor organisation address

West Glasgow Ambulatory Care Hospital, Dalnair Street, Glasgow, United Kingdom, G3 8SW

Public contact

Karen Carty, Cancer Research UK Clinical Trials Unit, 0044 141 301 7191, karen.carty@glasgow.ac.uk

Scientific contact

Jim Paul, Cancer Research UK Clinical Trials Unit, 0044 141 301 7188, james.paul@glasgow.ac.uk

Sponsor organisation name

University of Glasgow

Sponsor organisation address

University Avenue, Glasgow, United Kingdom, G12 8QQ

Public contact

Karen Carty, Cancer Research UK Clinical Trials Unit, 0044 141 301 7197, karen.carty@glasgow.ac.uk

Scientific contact

James Paul, Cancer Research UK Clinical Trials Unit, 0044 141 301 7188, james.paul@glasgow.ac.uk

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

24 Apr 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

09 Feb 2015

Global end of trial reached?

Yes

Global end of trial date

30 Apr 2015

Was the trial ended prematurely?

Yes

Main objective of the trial

The aim of the study is 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 cancer.

Protection of trial subjects

As part of the study patients required to attend for additional clinic visits and investigations which would be above those considered to be standard care. The visit schedule and the number and type of investigations were fully explained to patients verbally and in writing via the patient information sheet to ensure patients were fully aware what was in entailed in participating in the trial prior to them consenting to the study. The patient information sheet also fully explained the design of the study (randomised, double blind trial) that half of patients would receive study treatment (Cediranib) in addition to their chemotherapy with the other half receiving placebo in addition to their chemotherapy. The side effects of chemotherapy Carboplatin and Paclitaxel were explained in patient information sheet, as where the expected side effects for the investigational medicinal product Cediranib. All patients were closely monitored throughout the course of the study for adverse events and were advised to report adverse events to their study team as they arose. Specific measures were included in the protocol for management of adverse events related to Cediranib.

Background therapy

Evidence for comparator

Actual start date of recruitment

19 Aug 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 69

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study opened to recruitment on 03rd June 2010 and closed to recruitment on 31st July 2012. This study was opened to recruitment in the United Kingdom

Screening details

The screening period for the study was up to 28 days prior to randomisation. Prior to screening investigations commencing patient must have provided informed consent to participate in the study. Patients treated with potent inhibitors of CYP3A4 and 2C8 were excluded from the trial if they had received these within 2 wks of 1st planned dose.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

Matched placebo provided for oral drug

Are arms mutually exclusive

Yes

Control

Arm description

Placebo

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Patients received either treatment drug [Cediranib] 20 mg daily or placebo daily throughout 6 cycles of chemotherapy treatment (Approx 18 weeks of chemotherapy) following completion of chemotherapy patients continued to receive either treatment drug or placebo daily until disease progression.

Experimental

Arm description

Cediranib

Arm type

Experimental

Investigational medicinal product name

Cediranib (AZD2171)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Patients received either treatment drug (20mg) of placebo daily throughout 6 cycles of chemotherapy treatment (approx. 18 weeks of chemotherapy) following completion of chemotherapy patients continued to receive either treatment drug or placebo daily until disease progression

Number of subjects in period 1	Control	Experimental
Started	35	34
Completed	31	30
Not completed	4	4
Consent withdrawn by subject	2	2
No post-baseline data	-	2
Lost to follow-up	2	-

Baseline characteristics

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Reporting group title

Control

Reporting group description

Placebo

Reporting group title

Experimental

Reporting group description

Cediranib

Reporting group values	Control	Experimental	Total
Number of subjects	35	34	69
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	35	30	65
From 65-84 years	0	4	4
85 years and over	0	0	0
Age continuous
Units: years
median (inter-quartile range (Q1-Q3))	44 (34 to 53)	43.5 (37 to 60)	-
Gender categorical
Units: Subjects
Female	35	34	69
Male	0	0	0
ECOG Performance Status at Randomisation
Minimisation factor: ECOG Performance Status at Randomisation
Units: Subjects
ECOG 0	14	17	31
ECOG 1	21	17	38
Number of lines of previous treatment
Minimisation factor: Number of lines of previous treatment
Units: Subjects
0 lines	6	6	12
1 line	29	28	57
Disease site
Minimisation factor: Disease site
Units: Subjects
Local relapse only	3	6	9
Extra pelvic metastases only	12	9	21
Local relapse and extra pelvic metastases	20	19	39
Disease-free survival after primary therapy/primary stage IVb
Minimisation factor: Disease-free survival after primary therapy/primary stage IVb
Units: Subjects
<=12 months	16	14	30
>12 months	16	17	33
Treatment naive stage IVb	3	3	6

Subject analysis set title

Intention-to-treat

Subject analysis set type

Intention-to-treat

Subject analysis set description

All patients randomised

Subject analysis set title

Safety

Subject analysis set type

Safety analysis

Subject analysis set description

All randomised patients who received at least 1 dose of study medication

Subject analysis sets values	Intention-to-treat	Safety
Number of subjects	69	67
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	65	63
From 65-84 years	4	4
85 years and over	0	0
Age continuous
Units: years
median (inter-quartile range (Q1-Q3))	44 (35 to 57)	44 (35 to 57)
Gender categorical
Units: Subjects
Female	69	67
Male	0	0
ECOG Performance Status at Randomisation
Minimisation factor: ECOG Performance Status at Randomisation
Units: Subjects
ECOG 0	31
ECOG 1	38
Number of lines of previous treatment
Minimisation factor: Number of lines of previous treatment
Units: Subjects
0 lines	12
1 line	57
Disease site
Minimisation factor: Disease site
Units: Subjects
Local relapse only	9
Extra pelvic metastases only	21
Local relapse and extra pelvic metastases	39
Disease-free survival after primary therapy/primary stage IVb
Minimisation factor: Disease-free survival after primary therapy/primary stage IVb
Units: Subjects
<=12 months	30
>12 months	33
Treatment naive stage IVb	6

End points

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Reporting group title

Control

Reporting group description

Placebo

Reporting group title

Experimental

Reporting group description

Cediranib

Subject analysis set title

Intention-to-treat

Subject analysis set type

Intention-to-treat

Subject analysis set description

All patients randomised

Subject analysis set title

Safety

Subject analysis set type

Safety analysis

Subject analysis set description

All randomised patients who received at least 1 dose of study medication

Primary: Progression-free survival

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End point title

Progression-free survival

End point description

End point type

Primary

End point timeframe

Patients were assessed after chemotherapy cycles 2, 4 and 6 and then every 2 months during follow-up

End point values	Control	Experimental	Intention-to-treat
Number of subjects analysed	35	34	69
Units: months
median (confidence interval 80%)	6.7 (6.2 to 7.2)	8.1 (7.4 to 8.8)	7.2 (6.7 to 7.7)

Cox

Statistical analysis description

Cox proportional hazards model incorporating study stratification factors

Comparison groups

Experimental v Control

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

= 0.032 ^[2]

Method

Regression, Cox

Parameter type

Hazard ratio (HR)

Point estimate

0.58

Confidence interval

level

80%

sides

2-sided

lower limit

0.4

upper limit

0.85

Notes
[1] - Cox
[2] - 1-sided, 20% significance level

Adverse events

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Timeframe for reporting adverse events

Adverse events were followed until resolution or for at least 30 days after discontinuation of study medication, whichever came first, or until toxicity was resolved to baseline or < Grade 1, or until the toxicity was considered to be irreversible

Adverse event reporting additional description

Adverse events were reported following every cycle of chemotherapy and every 2 months during follow-up

Assessment type

Systematic

Dictionary name

NCI-CTCAE

Dictionary version

4.0

Reporting group title

Control

Reporting group description

Placebo

Reporting group title

Experimental

Reporting group description

Cediranib

Serious adverse events	Control	Experimental
Total subjects affected by serious adverse events
subjects affected / exposed	18 / 35 (51.43%)	19 / 32 (59.38%)
number of deaths (all causes)	27	25
number of deaths resulting from adverse events	0	1
Investigations
Creatinine increased
subjects affected / exposed	4 / 35 (11.43%)	0 / 32 (0.00%)
occurrences causally related to treatment / all	4 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	0 / 35 (0.00%)	4 / 32 (12.50%)
occurrences causally related to treatment / all	0 / 0	3 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Platelet count decreased
subjects affected / exposed	0 / 35 (0.00%)	3 / 32 (9.38%)
occurrences causally related to treatment / all	0 / 0	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Sinus tachycardia
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Peripheral sensory neuropathy
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	6 / 35 (17.14%)	2 / 32 (6.25%)
occurrences causally related to treatment / all	4 / 7	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 35 (0.00%)	5 / 32 (15.63%)
occurrences causally related to treatment / all	0 / 0	5 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences causally related to treatment / all	0 / 0	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Fever
subjects affected / exposed	4 / 35 (11.43%)	6 / 32 (18.75%)
occurrences causally related to treatment / all	1 / 4	2 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Pain
subjects affected / exposed	2 / 35 (5.71%)	3 / 32 (9.38%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 35 (5.71%)	4 / 32 (12.50%)
occurrences causally related to treatment / all	1 / 2	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 35 (0.00%)	4 / 32 (12.50%)
occurrences causally related to treatment / all	0 / 0	2 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	2 / 35 (5.71%)	6 / 32 (18.75%)
occurrences causally related to treatment / all	1 / 3	8 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Nausea
subjects affected / exposed	3 / 35 (8.57%)	3 / 32 (9.38%)
occurrences causally related to treatment / all	3 / 4	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 35 (0.00%)	4 / 32 (12.50%)
occurrences causally related to treatment / all	0 / 0	3 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Colonic perforation
subjects affected / exposed	0 / 35 (0.00%)	1 / 32 (3.13%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	1 / 1
Reproductive system and breast disorders
Vaginal haemorrhage
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	0 / 35 (0.00%)	4 / 32 (12.50%)
occurrences causally related to treatment / all	0 / 0	2 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Pleuritic pain
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Urinary tract obstruction
subjects affected / exposed	2 / 35 (5.71%)	0 / 32 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Infections and infestations - Other
subjects affected / exposed	0 / 35 (0.00%)	4 / 32 (12.50%)
occurrences causally related to treatment / all	0 / 0	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Lung infection
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	2 / 35 (5.71%)	2 / 32 (6.25%)
occurrences causally related to treatment / all	0 / 3	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 35 (0.00%)	3 / 32 (9.38%)
occurrences causally related to treatment / all	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Hypomagnesaemia
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Control	Experimental
Total subjects affected by non serious adverse events
subjects affected / exposed	35 / 35 (100.00%)	32 / 32 (100.00%)
Vascular disorders
Hot flush
subjects affected / exposed	2 / 35 (5.71%)	0 / 32 (0.00%)
occurrences all number	2	0
Hypertension
subjects affected / exposed	9 / 35 (25.71%)	18 / 32 (56.25%)
occurrences all number	13	40
Lymphoedema
subjects affected / exposed	4 / 35 (11.43%)	0 / 32 (0.00%)
occurrences all number	9	0
General disorders and administration site conditions
Edema limbs
subjects affected / exposed	6 / 35 (17.14%)	5 / 32 (15.63%)
occurrences all number	11	7
Fatigue
subjects affected / exposed	30 / 35 (85.71%)	31 / 32 (96.88%)
occurrences all number	119	146
Flu like symptoms
subjects affected / exposed	2 / 35 (5.71%)	2 / 32 (6.25%)
occurrences all number	2	5
Injection site reaction
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	6
Pain
subjects affected / exposed	20 / 35 (57.14%)	19 / 32 (59.38%)
occurrences all number	35	39
Reproductive system and breast disorders
Pelvic pain
subjects affected / exposed	3 / 35 (8.57%)	0 / 32 (0.00%)
occurrences all number	3	0
Vaginal discharge
subjects affected / exposed	6 / 35 (17.14%)	0 / 32 (0.00%)
occurrences all number	15	0
Vaginal haemorrhage
subjects affected / exposed	0 / 35 (0.00%)	3 / 32 (9.38%)
occurrences all number	0	3
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	5 / 35 (14.29%)	5 / 32 (15.63%)
occurrences all number	9	7
Dyspnoea
subjects affected / exposed	6 / 35 (17.14%)	9 / 32 (28.13%)
occurrences all number	11	16
Epistaxis
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	2
Hoarseness
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	3
Sore throat
subjects affected / exposed	3 / 35 (8.57%)	0 / 32 (0.00%)
occurrences all number	3	0
Psychiatric disorders
Anxiety
subjects affected / exposed	2 / 35 (5.71%)	0 / 32 (0.00%)
occurrences all number	3	0
Insomnia
subjects affected / exposed	3 / 35 (8.57%)	4 / 32 (12.50%)
occurrences all number	4	4
Investigations
Creatinine increased
subjects affected / exposed	2 / 35 (5.71%)	0 / 32 (0.00%)
occurrences all number	2	0
Neutrophil count decreased
subjects affected / exposed	4 / 35 (11.43%)	4 / 32 (12.50%)
occurrences all number	4	4
Weight loss
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	3
White blood cell decreased
subjects affected / exposed	0 / 35 (0.00%)	3 / 32 (9.38%)
occurrences all number	0	5
Cardiac disorders
Palpitations
subjects affected / exposed	2 / 35 (5.71%)	0 / 32 (0.00%)
occurrences all number	3	0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	7
Dysgeusia
subjects affected / exposed	0 / 35 (0.00%)	3 / 32 (9.38%)
occurrences all number	0	9
Headache
subjects affected / exposed	3 / 35 (8.57%)	6 / 32 (18.75%)
occurrences all number	4	9
Paresthesia
subjects affected / exposed	4 / 35 (11.43%)	0 / 32 (0.00%)
occurrences all number	4	0
Peripheral motor neuropathy
subjects affected / exposed	5 / 35 (14.29%)	7 / 32 (21.88%)
occurrences all number	5	12
Peripheral sensory neuropathy
subjects affected / exposed	16 / 35 (45.71%)	18 / 32 (56.25%)
occurrences all number	56	70
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	8 / 35 (22.86%)	4 / 32 (12.50%)
occurrences all number	17	8
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	4 / 35 (11.43%)	6 / 32 (18.75%)
occurrences all number	9	8
Constipation
subjects affected / exposed	23 / 35 (65.71%)	20 / 32 (62.50%)
occurrences all number	40	38
Diarrhoea
subjects affected / exposed	18 / 35 (51.43%)	29 / 32 (90.63%)
occurrences all number	29	130
Dry mouth
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	5
Dyspepsia
subjects affected / exposed	2 / 35 (5.71%)	2 / 32 (6.25%)
occurrences all number	3	2
Mucositis oral
subjects affected / exposed	11 / 35 (31.43%)	12 / 32 (37.50%)
occurrences all number	14	19
Nausea
subjects affected / exposed	23 / 35 (65.71%)	23 / 32 (71.88%)
occurrences all number	59	63
Vomiting
subjects affected / exposed	15 / 35 (42.86%)	15 / 32 (46.88%)
occurrences all number	24	27
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	21 / 35 (60.00%)	17 / 32 (53.13%)
occurrences all number	84	62
Pain of skin
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	2
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	2
Pruritus
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	2
Rash acneiform
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	2
Rash maculo-papular
subjects affected / exposed	2 / 35 (5.71%)	2 / 32 (6.25%)
occurrences all number	7	2
Renal and urinary disorders
Cystitis noninfective
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	2
Haematuria
subjects affected / exposed	3 / 35 (8.57%)	3 / 32 (9.38%)
occurrences all number	7	6
Proteinuria
subjects affected / exposed	10 / 35 (28.57%)	11 / 32 (34.38%)
occurrences all number	22	27
Urinary tract obstruction
subjects affected / exposed	2 / 35 (5.71%)	0 / 32 (0.00%)
occurrences all number	2	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	5 / 35 (14.29%)	5 / 32 (15.63%)
occurrences all number	15	7
Back pain
subjects affected / exposed	12 / 35 (34.29%)	6 / 32 (18.75%)
occurrences all number	27	17
Myalgia
subjects affected / exposed	8 / 35 (22.86%)	7 / 32 (21.88%)
occurrences all number	22	7
Pain in extremity
subjects affected / exposed	2 / 35 (5.71%)	2 / 32 (6.25%)
occurrences all number	2	2
Infections and infestations
Infections and infestation - Other
subjects affected / exposed	3 / 35 (8.57%)	0 / 32 (0.00%)
occurrences all number	6	0
Skin infection
subjects affected / exposed	2 / 35 (5.71%)	0 / 32 (0.00%)
occurrences all number	2	0
Tooth infection
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	2
Upper respiratory infection
subjects affected / exposed	2 / 35 (5.71%)	3 / 32 (9.38%)
occurrences all number	2	3
Urinary tract infection
subjects affected / exposed	8 / 35 (22.86%)	6 / 32 (18.75%)
occurrences all number	9	10
Vaginal infection
subjects affected / exposed	0 / 35 (0.00%)	2 / 32 (6.25%)
occurrences all number	0	2
Metabolism and nutrition disorders
Anorexia
subjects affected / exposed	5 / 35 (14.29%)	9 / 32 (28.13%)
occurrences all number	10	27
Hypomagnesaemia
subjects affected / exposed	0 / 35 (0.00%)	3 / 32 (9.38%)
occurrences all number	0	5

More information

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Were there any global substantial amendments to the protocol? Yes

04 Apr 2012

The protocol for the study was amended to reduce the sample size of the study from 130 patients to 80 patients. This amendment was made as result of AstraZeneca manufacturers of cediranib informing following negative results in other studies using Cediranib they had no plans to further develop the drug or manufacture further supplies of the drug. Due to this AZ informed they would require the majority of patients on CIRCCa to have completed study treatment by end of December 2012, they had confirmed they would commit to supply cediranib to patients for at least a further 6 months after this and any patients who are clearly continuing to benefit beyond that point. Based on this information the implications of this in relation to CIRCCa were discussed with the Independent Data Monitoring Committee (DMC) and Trial Steering Committee (TSC). The DMC and TSC carefully reviewed the CIRCCa documentation (Protocol and Patient Information Sheet/Consent Form) in relation to the information received from AZ, taking into account the associated translational aspects of CIRCCa .After carefully considering and taking into account all the information, the DMC and TSC endorsed the scientific importance of the study and felt that it should continue. They gave the following recommendations: If feasible should consider reducing the sample size for the study to ensure completion of the study by December 2012. The statistics for the study were reviewed, for the study to deliver a study with 80% power, 20% 1-sided level of statistical significance, the study will require at least 80 patients. Protocol was amended accordingly to reduce the sample size.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical Trial Results:
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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Progression-free survival

Primary: Progression-free survival

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: 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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Progression-free survival

Primary: Progression-free survival

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
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