A trial looking at cediranib for ovarian cancer that has come back (ICON6)

ISRCTN	ISRCTN68510403
DOI	https://doi.org/10.1186/ISRCTN68510403
EudraCT/CTIS number	2007-001346-41
ClinicalTrials.gov number	NCT00532194
Secondary identifying numbers	ACTRN1261000016003

Submission date: 22/03/2007
Registration date: 13/08/2007
Last edited: 22/11/2023

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

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-standard-treatment-with-or-without-cediranib-for-ovarian-fallopian-tube-or-primary-peritoneal-cancer-that-has-come-back

Study website

Contact information

Prof Jonathan Ledermann
Scientific

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

Ms Liz Clark
Public

ICON6 Trial Manager
University College London
Cancer Research UK and UCL Cancer Trials Centre
90 Tottenham Court Road
London
W1T 4TJ
United Kingdom

Email	elizabeth.clark@ucl.ac.uk

Study information

Study design	Randomised three-arm double-blind placebo-controlled multicentre phase III trial
Primary study design	Interventional
Secondary study design	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	A double-blind, placebo-controlled, three-arm, randomised, multi-centre Gynaecologic Cancer InterGroup trial of cediranib (AZD2171), in combination with platinum-based chemotherapy and as a single agent maintenance therapy, in women with ovarian cancer relapsing more than 6 months following completion of first-line platinum-based treatment
Study acronym	ICON6 (International Collaborative Ovarian Neoplasm 6)
Study hypothesis	Current hypothesis as of 13/03/2015: That cediranib has an influence on progression-free survival when comparing patients receiving chemotherapy alone with patients receiving chemotherapy and cediranib (AZD2171). Previous hypothesis: Over three separate trial stages the study hypotheses are: Stage 1: That it is safe to add a once daily tablet of cediranib to standard platinum-based chemotherapy Stage 2: That cediranib has an influence on progression free survival when comparing patients receiving chemotherapy alone with patients receiving chemotherapy and cediranib (AZD2171) Stage 3: 1. That cediranib has an effect on overall survival when taken at the same time as chemotherapy (placebo versus active), and when taken at the same time and then continued as a maintenance treatment (placebo versus active) 2. If the first Stage 3 assessments shows the product is effective, that cediranib has an effect on overall survival when taken at the same time as chemotherapy compared with at the same time and then continued as a maintenance treatment
Ethics approval(s)	Oxfordshire Research Ethics Committee B, 16/07/2007, ref: 07/H0605/76
Condition	Relapsed platinum-sensitive ovarian cancer
Intervention	Current interventions as of 13/03/2015: Patients in Arm A (the reference arm) will receive standard platinum-based chemotherapy plus a daily oral placebo tablet for the duration of the chemotherapy and then until protocol defined disease progression occurs. Patients in Arm B (concurrent cediranib arm) will also receive standard chemotherapy plus daily oral cediranib during chemotherapy only, and then an oral daily placebo tablet until protocol defined disease progression or toxicity limiting treatment occurs. Patients in Arm C (concurrent and maintenance cediranib arm) will also receive standard chemotherapy plus oral cediranib daily during chemotherapy and until protocol defined disease progression or toxicity limiting treatment occurs. Previous interventions: Patients in Arm A (the reference arm) will receive standard platinum-based chemotherapy plus a daily oral placebo tablet for the duration of the chemotherapy and then for up to 18 months from the time of randomisation, or until protocol defined disease progression occurs. Patients in Arm B (concurrent cediranib arm) will also receive standard chemotherapy plus daily oral cediranib during chemotherapy only, and then an oral daily placebo tablet for up to 18 months from the time of randomisation, or until protocol defined disease progression or toxicity limiting treatment occurs. Patients in Arm C (concurrent and maintenance cediranib arm) will also receive standard chemotherapy plus oral cediranib daily during chemotherapy and then continued for up to 18 months from the time of randomisation, or until protocol defined disease progression or toxicity limiting treatment occurs. The starting dose of cediranib is 30 mg taken orally once daily. This will be down titrated if required on medical assessment to 20 mg and then 15 mg.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Cediranib (also known as AZD2171 and recentin)
Primary outcome measure	Current primary outcome measures as of 13/03/2015: Progression-free survival (PFS) in arms A vs C Previous primary outcome measures: Stage 1: Safety Stage 2: Progression free survival Stage 3: Overall survival Data for the outcomes above will be collected approximately 3 weekly during chemotherapy, 6 weekly after chemotherapy up to 18 months, 3 monthly up to 3 years, 6 monthly during years 4 and 5, then annually until protocol defined disease progression or death.
Secondary outcome measures	Current secondary outcome measures as of 13/03/2015: 1. Progression-free survival (PFS) across arms A, B and C 2. Overall survival (OS) 3. Toxicity 4. Quality of Life (QoL) Previous secondary outcome measures: Stage 1: None Stage 2: Overall survival and toxicity Stage 3: Progression free survival, toxicity and quality of life Quality of life assessment will be made using EORTC QLQ-C30 version 3 and EORTC QLQ-OV28. This information will be supplemented by health questionnaire EQ-5D. Other outcome measures will be assessed by clinical interview, blood tests and CT scans. Data for the outcomes above will be collected approximately 3 weekly during chemotherapy, 6 weekly after chemotherapy up to 18 months, 3 monthly up to 3 years, 6 monthly during years 4 and 5, then annually until protocol defined disease progression or death.
Overall study start date	01/07/2007
Overall study end date	31/12/2016

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target number of participants	470
Participant inclusion criteria	1. Females aged 18 years or older with previous histologically proven diagnosis of: 1.1. Epithelial ovarian carcinoma 1.2. Fallopian tube carcinoma 1.3. Primary serous peritoneal carcinoma Relapsing more than 6 months after completion of first-line platinum-based chemotherapy 2. Signed informed consent and ability to comply with the protocol 3. Ability to commence treatment within 2 weeks of randomisation 4. Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI) proven relapsed disease, more than six months since completion of first-line platinum-based chemotherapy 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 6. Life expectancy more than 12 weeks 7. If there is a past history of a solid tumour, this must have been treated curatively more than five years ago with no evidence of recurrence 8. Adequate bone marrow function 8.1. Absolute Neutrophil Count (ANC) greater than or equal to 1.5 x 109/l 8.2. Platelets (Plt) greater than or equal to 100 x 109/l 8.3. Haemoglobin (Hb) greater than or equal to 9g/dl (can be post transfusion) 9. Adequate liver function (within 14 days before randomisation) 9.1. Serum bilirubin (BR) = 1.5 x Upper Limit of Normal (ULN) 9.2. Serum transaminases = 2.5 x ULN 10. Adequate renal function 10.1. Serum creatinine = 1.5 ULN 10.2. Urine dipstick for proteinuria less than 2+. If urine dipstick is greater than or equal to 2+ on two occasions more than one week apart then a 24 hour urine must demonstrate less than or equal to 1 g of protein in 24 hours
Participant exclusion criteria	1. Non-epithelial ovarian cancer, including malignant mixed Mullerian tumours and mucinous carcinoma of the peritoneum 2. Poorly controlled hypertension (persistently elevated >150/100 mmHg despite anti-hypertensive medication) 3. History of inflammatory bowel disease (Crohn's disease or ulcerative colitis) 4. Malignancies other than ovarian cancer within 5 years prior to randomisation, except for adequately treated carcinoma in situ of the cervix and/or basal cell skin cancer. Patients who have a past history of a solid tumour, treated curatively, more than five years prior to randomisation, with no evidence of recurrence, are still eligible to enter ICON6 5. Previous radiotherapy within 21 days prior to randomisation 6. Treatment with any other investigational agent within 30 days prior to entering this trial. Patients are still eligible for entry into ICON6 if they have received previous treatment for ovarian cancer with either bevacizumab, erlotinib, or a Cox-2 inhibitor as long as more than 30 days have elapsed since the last treatment 7. Arterial thrombotic event (including Transient Ischaemic Attack [TIA], cerebrovascular accident [CVA) and peripheral arterial embolus) within the previous 12 months 8. Gastrointestinal (GI) impairment that could affect ability to take, or adsorption of, oral medicines including sub acute or complete bowel obstruction 9. Known hypersensitivity to AZD2171 or other Vascular Endothelial Growth Factor (VEGF) inhibitors 10. Major surgery within 2 weeks before entry into the trial 11. Significant haemorrhage of >30 ml in a single episode within 3 months or any haemoptysis 12. Evidence of severe or uncontrolled cardiac disease 12.1. Myocardial Infarct (MI) or unstable angina within 12 months 12.2. New York Health Association (NYHA) = grade 2 Congestive Heart Failure (CHF) 12.3. Cardiac ventricular arrhythmias requiring medication 12.4. History of 2nd or 3rd degree atrioventricular conduction defects 13. Prolonged QTc (corrected) interval of >470 msec on electrocardiogram (ECG), or a family history of long QT syndrome 14. Persisting = Grade 2 CTC (Common Toxicity Criteria) toxicity (except alopecia and neuropathy) from previous anti-cancer treatment. If peripheral sensory or motor neuropathy = grade 2 then paclitaxel can be omitted from the chemotherapy at the discretion of the treating physician 15. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory in the case of suspected brain metastases. Spinal MRI is mandatory in the case of suspected spinal cord compression. Patients with unstable untreated brain or meningeal metastases are not eligible 16. Inability to attend or comply with treatment or follow-up scheduling 17. 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 18. Fertile women of childbearing potential not willing to use adequate contraception for the duration of trial treatment and at least 6 months after 19. Any other severe uncontrolled medical condition or disease
Recruitment start date	29/11/2007
Recruitment end date	23/12/2011

Locations

Countries of recruitment

Australia
Canada
England
New Zealand
Spain
United Kingdom

Study participating centre

University College Hospital

London
NW1 2BU
United Kingdom

Sponsor information

Medical Research Council (UK)
Government

20 Park Crescent
London
W1B 1AL
United Kingdom

Website	http://www.mrc.ac.uk
"ROR"	https://ror.org/03x94j517

Funders

Funder type

Industry

Cancer Research UK (ref: C444/A6862)
Private sector organisation / Other non-profit organizations

Alternative name(s): CR_UK, Cancer Research UK - London, CRUK
Location: United Kingdom

AstraZeneca (ref: D8480C00037) (International)
Government organisation / For-profit companies (industry)

Alternative name(s): AstraZeneca PLC, Pearl Therapeutics
Location: United Kingdom

Medical Research Council
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

National Health and Medical Research Council
Government organisation / National government

Alternative name(s): NHMRC
Location: Australia

Results and Publications

Intention to publish date	30/06/2015
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Primary outcome presented at European Cancer Congress 2013 (http://2013.europeancancercongress.org/Scientific-Programme/Abstract-search.aspx?abstractid=8897), full manuscript anticipated Q2 2015 in parallel with QoL data. Mature OS analysis to be conducted when greater than 80% of deaths have occurred.
IPD sharing plan	The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Plain English results				No	Yes
Results article	results	27/09/2011		Yes	No
Results article	results	12/03/2016		Yes	No
Results article	quality of life results	15/07/2017		Yes	No
Results article	results	01/10/2019	02/09/2020	Yes	No
Results article		01/04/2021	01/11/2021	Yes	No

Editorial Notes

22/11/2023: Updated Cancer Research UK lay results summary link added to the plain English summary.
01/11/2021: Publication reference added.
02/09/2020: Publication reference added.
26/10/2018: Cancer Research UK lay results summary link added to the plain English summary.
27/03/2017: Publication reference added.
31/03/2016: Publication reference added.
13/03/2015: The following changes were made to the trial record:
1. The study design was changed from 'Randomised three-arm three-stage double-blind placebo-controlled multicentre phase III trial' to 'Randomised three-arm double-blind placebo-controlled multicentre phase III trial'
2. The overall trial end date was changed from 31/07/2013 to 31/12/2016.
3. The target number of participants was changed from 2000 to 470.
4. Austria, Belgium, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Norway, Serbia and Sweden were removed from the countries of recruitment.
5. Medical Research Council (UK) and NHMRC (Cancer Australia) were added as funders.