MRC Clinical Trials Unit at UCL
Institute of Clinical Trials & Methodology
90 High Holborn 2nd Floor
London
WC1V 6LJ
Email: ICON6@ctu.mrc.ac.uk
News
ICON6 at ASCO 2017
The ICON6 Chief Investigator, Professor Jonathan Ledermann, presented the results of the updated Overall Survival (OS) analysis at the annual meeting of the American Society of Clinical Oncology (ASCO) on June 2nd 2017. The results showed a 7.4 month increase in OS among patients with platinum sensitive, relapsed ovarian cancer who were given cediranib concurrently with chemotherapy and continued as part of maintenance when compared to standard chemotherapy only. The slides presented at the meeting can be viewed here.
The presentation was also selected to be included in the Best of ASCO program and was reported on in the ASCO Daily News report.
Statement on the Zemfirza (cediranib) marketing authorisation application withdrawal
On 19 September 2016, AstraZeneca officially notified the Committee for Medicinal Products for Human Use (CHMP) that it wishes to withdraw its application for a marketing authorisation for Zemfirza (the trade name of cediranib), for the treatment of ovarian cancer. The European Medicines Agency has now posted questions and answers about this on their website.
The ICON6 trial conducted by the Medical Research Council (MRC) Clinical Trials Unit at UCL was a high quality international trial that found that cediranib increased progression-free survival by 2.5 months in patients with platinum sensitive relapsed ovarian cancer.
The ICON6 trial was conducted to a high standard. It was not designed as a licensing trial, so was conducted in line with the principles of GCP, rather than full ICH-GCP processes. Sensitivity analyses assessing the impact of the issues identified in the inspection showed they made only a minor and inconsequential difference to the results. We are confident that the ICON6 results are reliable: cediranib improves PFS for women with platinum sensitive relapsed ovarian cancer.
One of the MRC Clinical Trials Unit’s main aims is to deliver swifter and more effective translation of scientific research into patient benefits. It is very disappointing that there will now be a delay in bringing the benefits of cediranib to a group of patients who have limited treatment options
Statement on the cediranib marketing authorisation application withdrawal
The ICON6 trial conducted by the Medical Research Council (MRC) Clinical Trials Unit at UCL was a high quality international trial that found that cediranib increased progression-free survival by 2.5 months in patients with platinum sensitive relapsed ovarian cancer.
“One of the Clinical Trial Unit’s main aims is to deliver swifter and more effective translation of scientific research into patient benefits. It is very disappointing that there will now be a delay in bringing the benefits of Cediranib to a group of patients who have limited treatment options".
Updated ICON6 Final Progression Free Survival analysis
The Lancet has recently published an update to the progression-free survival (PFS) data first presented at the European Society of Medical Oncology congress (ESMO) 2013. These results show that there is a benefit to be derived from the use of cediranib (AZD171) when given concurrently with chemotherapy and continued as maintenance for patients with platinum sensitive ovarian cancer when compared to standard chemotherapy only. The secondary endpoint of overall survival will require more follow up before analysis.
In July 2015, Cediranib (AZD171) was submitted by AstraZeneca for marketing authorisation from the European Medicines Agency. A decision is expected in 2016.
We would like to take this opportunity to thank all patients and their families for their contribution, and all trial personnel for their support.
ICON6 Final Progression Free Survival analysis
Presented at The European Cancer Congress (ECCO 17 - ESMO 38 - ESTRO 32) 2013
The ICON6 Chief Investigator Professor Jonathan Ledermann presented the results of the final Progression Free Survival analysis at The European Cancer Congress in Amsterdam on 30th September 2013. The full abstract is available at the link below, just enter "ICON6" into the field labelled 'Abstract Title' and then click the 'Search' button to find the abstract.
ICON6 Abstract for The European Cancer Congress 2013
ICON6 selected for The European Cancer Congress
ICON6 was selected for inclusion in The European Cancer Congress media programme. The full press release is available at the link below:
ICON6 Press Release for The European Cancer Congress 2013
A video of the ICON6 Chief Investigator Professor Jonathan Ledermann presenting the Progression Free Survival results of the ICON6 trial to the media is also available at the link below:
Video of ICON6 Presentation to the media at The European Cancer Congress 2013
Final Analysis Begins April 2013
The final analysis of ICON6 began in April 2013. The trial statistician is analysing the data to see if cediranib has an effect on ovarian cancer, and whether cediranib increases the length of time women are free of the disease following chemotherapy treatment. We will then know whether the new treatment (cediranib plus chemotherapy) is better than the current standard treatment (chemotherapy alone).
ICON6 Unblinded April 2013
ICON6 is a ‘double-blinded’ trial which means that during treatment neither patients, nor their study doctor knew if patients were taking cediranib or placebo. Tablets containing the active drug and placebo were designed to look, taste and smell the same. Now that the final analysis is underway all sites will be informed of which group each patient joined.
Patients wishing to find out which treatment they received during the ICON6 trial will be informed at their next scheduled clinic visit.
Recruitment Target Reached Dec 2011
The revision to the ICON6 statistical plan and the proposal to continue recruitment to achieve the new planned sample size of 470 patients was supported by the IDMC. The ICON6 Protocol and Patient Information Sheet have been amended and were submitted to Ethics and the MHRA on 11th November 2011. The new documents will be circulated to Investigators once approval has been obtained. All patients receiving trial medication will need to be re-consented with the updated Patient Information Sheet.
The target accrual was reached in early December 2011 and recruitment to ICON6 is now closed. We would like to take this opportunity to thank all trial personnel for your hard efforts and support in reaching the target recruitment.
IDMC Update July 2011
The Independent Data Monitoring Committee (IDMC) met recently (13th July 2011) to review the recent safety analysis of patients participating in ICON 6. We are pleased to confirm that no specific concerns were raised and the IDMC recommended the continuation of accrual with review of early efficacy data towards the end of 2011, as previously arranged.
Stage 2 of ICON6 trial began in April 2010
We are now taking on new recruiting sites
ICON6 opened in December 2007 in a limited number of sites in the UK and Canada. The first stage of the trial was to evaluate treatment toxicity. The trials Independent Data Monitoring Committee met in December 2009 and concluded that cediranib could be given without a pre-specified level of excess toxicity thus allowing accrual to continue into the second stage.
The second stage has now begun and will evaluate activity based progression-free survival, an intermediate outcome measure. If a certain pre-specified level of activity is demonstrated then accrual will continue into the third stage to investigate whether the addition of cediranib to standard chemotherapy confers a benefit on overall survival.
Stage 2 was launched in April 2010 following the approval of the protocol amendment (v6.0 Feb 2010). Approximately 40 new UK sites will open along with further sites in Canada (NCIC CTG) and also in Australia and New Zealand (ANZGOG). There is also interest in collaboration from other GCIG groups in Spain (GEICO), Italy (MaNGO & MITO) and Korea (KGOG).
Recent Protocol Amendments Protocol version 6.0 Feb 2010
Key changes:
- Inclusion of gemcitabine and platinum chemotherapy, which is becoming more widely used
- Patients allowed to continue taking Trial Drug (cediranib) beyond 18 months, if they have not progressed and both the patient and their treating clinician feels it may be of benefit to them to continue, until progression
- Updates to the Investigator Brochure (now version 13) and updates to management of asymptomatic thrombotic embolisms
- Updates to management of unblinding post progression and updates to scheduling in the trial
Interested New Sites The ICON6 Site Selection Checklist should be completed by all new interested sites. Experience in the treatment of ovarian cancer and of conducting trials to GCP with appropriate clinical and research staff support is very important in this trial as cediranib is an unlicensed product. Sites already participating in ICON7 will already be familiar with these criteria.
If you would like any further information about ICON6 or would like to become a recruiting site then please click here.
Icon 6 opened in December 2006 in a limited number of sites
The first stage of the trial was to evaluate treatment toxicity. The trials Independent Data Monitoring Committee met in December 2009 and concluded that cediranib could be given without a pre-specified level of excess toxicity thus allowing accrual to continue into the second stage.
The second stage, which is about to recruit patients, will evaluate activity based progression-free survival, an intermediate outcome measure. If a certain pre-specified level of activity is demonstrated then accrual will continue into the third stage to investigate whether the addition of cediranib to standard chemotherapy confers a benefit on overall survival.
Stage 2 will be launched once the new protocol amendment is approved with approximately 40 new UK sites opening along with sites in Australia and New Zealand (ANZGOG), Spain (GEICO), Italy (MANGO & MITO), and other European countries in collaboration with the EORTC.
ICON6