ICON8: An international phase III randomised trial of dose-fractionated chemotherapy compared to standard three-weekly chemotherapy, following immediate primary surgery or as part of delayed primary surgery, for women with newly diagnosed epithelial ovarian, fallopian tube or primary peritoneal cancer
ISRCTN: 10356387
EUDRACT: 2010-022209-16
MREC: 11/LO/0043
The ICON8 trial is sponsored by the Medical Research Council. The Medical Research Council has delegated responsibility for the overall management of the ICON8 Trials Programme to the MRC CTU at UCL.
Queries relating to MRC sponsorship of this trial should be directed to: Director of MRC CTU at UCL, 90 High Holborn, London, WC1V 6LJ.
The trial took place in almost 100 UK hospitals as well as hospitals in Korea, the Republic of Ireland, Mexico, Australia and New Zealand.
Women joined the ICON8 trial between June 2011 and November 2014. So far, we have followed up how women were doing for at least 3 years.
The ICON8 study is testing how best to give chemotherapy to women with ovarian cancer. It compared having chemotherapy every week to the current standard of having chemotherapy once every three weeks. It aimed to see if weekly chemotherapy is better at delaying or preventing the disease getting worse and improving how long women live for.
Women who agreed to take part in the ICON8 study were split into 3 groups, at random.
People taking part in the ICON8 trial were:
1566 women took part in the ICON8 trial. The average age of women who joined ICON8 was 62, ranging from 22 to 84 years old. Most women had advanced ovarian cancer (stage IIIC or stage IV).
Women in ICON8 could have surgery before or part way through their chemotherapy. Most women did have surgery.
The chemotherapy medicines used in the ICON8 trial were the same for women in all three groups. All three groups had a combination of paclitaxel and carboplatin. The difference between the groups was how often these drugs were given.
Once women had agreed to join the trial, they were randomly allocated to one of the three groups. Women and their doctors knew which group they had been allocated to.
Many women in the study told us they had some side-effects. Side effects are unwanted medical events (such as headache) that happen during the study, and are reported because the trial doctor believes the side-effects were related to the treatment in the trial. Not all the people in this trial had side-effects.
The main severe side-effects were:
This difference was not big enough for us to be sure that it was due to the different treatment approaches rather than chance.
This difference was not big enough for us to be sure that it was due to the different treatment approaches rather than chance.
This difference is big enough for us to be confident that women in Group 2 were more likely to have severe anaemia than women in the other groups because of the treatment approach used in that group.
Women in Group 3 (who had weekly carboplatin) were more likely to have an allergic reaction to carboplatin than women who only had it once every three weeks (Groups 1 and 2). These reactions were mostly mild.
The ICON8 trial found no difference in how long it was until the cancer came back or got worse for women who had weekly chemotherapy, compared to women who had three weekly chemotherapy.
On average, women who had chemotherapy every three weeks (Group 1) had around 24 months before their cancer came back or got worse. Women who had carboplatin every three weeks, and paclitaxel every week (Group 2) had around 25 months before their cancer came back or got worse, on average. Women who had carboplatin and paclitaxel every week (Group 3) also had around 25 months, on average, before their cancer came back or got worse. This difference is not big enough for us to be confident that having weekly chemotherapy is better than having chemotherapy once every three weeks. These results are averages. This means some women have done better, with the disease not coming back or getting worse, and others have had their disease come back or get worse sooner.
We found no evidence of any subgroups of women taking part in ICON8 benefitting from weekly chemotherapy compared to three-weekly chemotherapy. We looked at subgroups including stage of disease, and whether chemotherapy was started before or after surgery.
Weekly chemotherapy was safe to give, but did not work better than 3 weekly chemotherapy as a first treatment for ovarian cancer. We think carboplatin and paclitaxel every 3 weeks should still be the standard treatment.
These results suggest that women like those in ICON8 with ovarian cancer are unlikely to benefit from having chemotherapy once a week rather than once every three weeks.
ICON8 did not include women who were so unwell they were confined to bed for more than half of every day, so we do not know if they apply to them.
These results will not change the way that future patients are treated. But they help doctors to understand more about how chemotherapy should be given to women with ovarian cancer. This may help them find other, better ways to treat ovarian cancer in the future.
The ICON8 trial will continue to follow-up women to answer the longer term question on whether weekly chemotherapy improves how long women live for.
A follow-on trial is now running called the ICON8B trial. ICON8B is looking at whether weekly chemotherapy is better than three-weekly chemotherapy for women who are also receiving the drug bevacizumab (also known as Avastin) in addition to chemotherapy.
The ICON8 trial is registered with the ISRCTN registry. The registration number is 10356387. You can see more details about the trial here http://www.isrctn.com/ISRCTN10356387
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