OCTOPUS
Research type
Research Study
Full title
OCTOPUS: Ovarian Cancer Trials of Weekly Paclitaxel - Umbrella Study A Randomised, Phase II Umbrella Trial of a Weekly Paclitxel +/- Novel Agents in Platinum-Resistant Ovarian Cancer
IRAS ID
169660
Contact name
Liz-Anne Lewsley
Contact email
Sponsor organisation
NHS Greater Glasgow & Clyde
Eudract number
2014-005221-12
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Research Summary - More than 4,200 women with ovarian cancer die from the disease every year in the UK. Most patients with relapsed ovarian cancer initially respond to chemotherapy but then the disease becomes resistant to treatment. Eventually, all patients develop relapse within 6 months from the end of last platinum containing chemotherapy- a term called platinum-resistance. The response rate to chemotherapy for women with platinum-resistant ovarian cancer is low (10-55%). The average time before the cancer worsens (‘median progression-free survival’) is approximately 4 months and overall survival is only 12 months. There is an urgent need to improve patient outcomes.
Chemotherapy using paclitaxel delivered weekly is a useful strategy. OCTOPUS is a phase II clinical trial framework for testing whether novel targeted agents (either as single agents or in combination with weekly paclitaxel-‘experimental’ arm) provide any promising activity signals in platinum-resistant ovarian cancer compared to weekly paclitaxel alone (standard care). This trial design allows for new targeted agents to be screened in the context of a rolling, randomised, placebo-controlled phase II setting. New agents will be introduced/removed from OCTOPUS by amendment thus reducing the study time and costs. In each randomised placebo controlled study, a total of 140 patients will be recruited and randomised in a 1:1 ratio to receive paclitaxel plus novel agent or paclitaxel plus placebo.
The aim of the trial is to investigate whether the experimental arm is superior to standard chemotherapy (paclitaxel), to determine the safety, quality of life and to explore whether markers predicting which patients are likely to benefit most can be found.
The first drug to be tested in combination with weekly paclitaxel is AZD2014. This oral drug blocks molecules called mTORC1 and 2 which are known to be involved in cancer growth. Early clinical trials have shown very promising results in ovarian cancer.
Lay Summary - OCTOPUS: Ovarian Cancer Trials of Weekly Paclitaxel - Umbrella Study A Randomised, Phase II Umbrella Trial of a Weekly Paclitxel +/- Novel Agents in Platinum-Resistant Ovarian Cancer
Background and study aims
At the time this study was designed, ovarian cancer was usually treated with surgery followed by chemotherapy. The chemotherapy often includes a platinum drug such as carboplatin. If a patients cancer gets worse within 6 months of having this treatment, it is called platinum resistant. Patients then may go on to have treatment with a taxane chemotherapy drug called paclitaxel, however sometimes the cancer starts to grow again, therefore researchers were looking at ways to delay this.
In this trial, we were looking at Vistusertib. This is a type of biological therapy. It is a cancer growth blocker and it stops signals that cancer cells use to divide and grow.Doctors know from research that having paclitaxel and Vistusertib together may control the cancer for longer, however they want to find out more.
The aims of the trial are to
• Find out if adding Vistusertib to weekly paclitaxel is a useful treatment for ovarian cancer
• Learn more about the side effects
• Find out how it affects quality of lifeWho carried out the research?
This study was Sponsored by NHS Greater Glasgow and Clyde/University of Glasgow and funded by AstraZeneca (who supplied the study drug free of charge also). This study was also endorsed by Cancer Research UK. The study was Co-ordinated by the Cancer Research UK Glasgow Clinical Trials Unit on behalf of NHS Greater Glasgow and Clyde/University of Glasgow.
The Chief Investigator was Professor Susana Banerjee, Professor in Women’s Cancers, The Royal Marsden NHS Foundation Trust.What public involvement there was in the study (how many people, what their relevant lived experience was, and what they did) There was public involvement at the onset of this study and feedback was received from patient groups regarding the patient information sheets prior to these being submitted for ethical approval. The Umbrella Trial Steering Committee within the Glasgow Oncology Clinical Trials Unit (who co-ordinated this trial) meets annually to oversee their portfolio of trials and there is patient representation on here. A translational committee was set up to manage the samples collected during this research and there is patient representation on here. We had engaged with patient representation going forward for any new arms of the study, however the study was closed before this could be taken any further.
Where and when the study took place
This study took place in 23 hospitals across the UK. The study started on 11th December 2012 and finished 28th February 2023 (recruitment took place from 17th January 2012 to 7th September 2017):The Beatson West of Scotland Cancer Centre, Glasgow Bristol Haematology and Oncology Centre The Christie Hospital NHS Trust, Manchester Churchill Hospital, Oxford Clatterbridge Cancer Centre, Wirral Guy’s and St Thomas’ Hospital, London Hammersmith Hospital, London Mount Vernon Cancer Centre, Northwood Musgrove Park Hospital, Taunton Ninewells Hospital, Dundee Nottingham City Hospital Royal Berkshire Hospital, Reading The Royal Marsden Hospital, Sutton & Chelsea Royal Sussex Hospital Royal United Hospital, Bath Southampton General Hospital St James’ University Hospital, Leeds University College London Hospital Western General Hospital, Edinburgh Worthing Hospital
Why was the research needed?
There is an urgent need to improve outcomes for patients with platinum-resistant ovarian cancer. The median progression-free survival for platinum-resistant disease is approximately 4 months and median overall survival is 12 months. Weekly paclitaxel is a useful strategy in platinum-resistant disease. OCTOPUS was an umbrella phase II framework for testing whether novel targeted agents show evidence of additional efficacy compared to a weekly paclitaxel control arm in platinum-resistant ovarian cancer.. The protocol consists of a generic main section and novel study drug specific sections. The novel study drug specific section will be amended when the current study completes and the novel drug is changed.There was only one arm of this study as the study team were unable to source a further novel drug and the study was terminated.
What were the main questions studied?
See above.Who participated in the study?
Suitable patients were female and were eligible if they met the following criteria:• A tissue sample taken shows ovarian cancer, fallopian tube cancer or primary peritoneal cancer that is high grade
• The cancer did not respond to platinum chemotherapy or continued to grow within 6 months of having this treatment (it is platinum resistant or platinum refractory)
• The cancer can be seen on a scan
• A sample of tissue that was removed when you had your ovarian cancer surgery is available
• You are willing to have a further tissue sample taken before you start treatment
• You are well enough to take part
• You have satisfactory blood test results
• You are willing to use reliable contraception during treatment and for 6 months afterwards if there is any chance that you could become pregnant
• You are at least 18 years oldWhat treatments or interventions did the participants take/receive?
Participants were randomised to receive one of the following treatments:
• Paclitaxel Day 1, Day 8 and Day 15 of a 28 day cycle (3 weeks on, 1 week off) + placebo (dummy drug)
• Paclitaxel Day 1, Day 8 and Day 15 of a 28 day cycle (3 weeks on, 1 week off) + VistusertibParticipants who consented to take part in OCTOPUS were also asked to undertake the following:
• A biopsy of their relapsed ovarian cancer – this was usually done using ultrasound or CT.
• Blood samples to allow extraction of normal DNA.
• Blood samples to allow storage of plasma.
• Permit researchers access to tumour material taken when they were first diagnosed.What medical problems (adverse reactions) did the participants have?
Most women who took part in this trial had at least 1 side effect. Most were mild or did not last long, but some women had side effects that were more severe.
The number of women who had more severe side effects was looked at. It was found that:
• 29 women (41%) in the paclitaxel and vistusertib group
• 26 women (37%) in the paclitaxel and dummy drug groupThe most common severe side effects for both groups included:
• an increased risk of infection
• tiredness (fatigue)More women in the paclitaxel and vistusertib group had these side effects.
Women who had paclitaxel and vistusertib also had mild to moderate problems with:
• stomach acid traveling up to the throat (reflux)
• a skin rashNo one in the paclitaxel and dummy drug group had these problems.
What happened during the study?
A total of 140 women joined this trial:
• 70 had paclitaxel and vistusertib
• 70 had paclitaxel and a dummy drug (placebo)The following was looked at:
• how long before the cancer started to grow again
• how long people lived
• how well the treatment workedThe results showed that there was no difference between the 2 groups.
What were the results of the study?
It was found that adding vistusertib to paclitaxel did not improve treatment for ovarian cancer.
It is suggested that biomarkers that predict who vistusertib could work best for should be looked at in more detail. It was found that low levels of a potential biomarker called PTEN was linked with how long before the cancer started to grow again. This was for people who had paclitaxel and vistusertib. This should be looked at in separate studies using similar drugs.Sometimes trials show a different treatment is not useful for a particular type or stage of cancer, however these trials still add to our knowledge and understanding of cancer and how to treat it.
How has this study helped patients and researchers?
This study has helped researchers provide information on what next steps should be taken into platinum resistant ovarian cancer patients and that more work requires to be done in this area.Details of any further research planned
This study was set up to allow for new arms to be opened when new drug became available. Unfortunately, since this arm closed to recruitment in 2018 we have been unsuccessful in obtaining any new drugs. Standard of care for these patients in the UK remains as weekly paclitaxel.Where can I learn more about this study?
A summary of the study results will be written (in English) and published on the Cancer Research UK About Cancer database and this can be found here.Information regarding the study is also available on the clinical trial register:
ISRCTN - ISRCTN16426935: OCTOPUS - ovarian cancer trials of weekly paclitaxelWe would like to thank the participants and their families that took part in this research. We would also like to thank all study investigators and staff from participating hospitals as well as the study team and study Sponsor.
REC name
London - Brighton & Sussex Research Ethics Committee
REC reference
15/LO/1302
Date of REC Opinion
14 Aug 2015
REC opinion
Favourable Opinion