ADIUVO version 1.0
Research type
Research Study
Full title
Efficacy of adjuvant mitotane in prolonging recurrence-free survival in patients with adrenocortical carcinoma at low-intermediate risk of recurrence
IRAS ID
71105
Contact name
Wiebke Arlt
Contact email
Sponsor organisation
University of Birmingham
Eudract number
2007-007262-38
Clinicaltrials.gov Identifier
Research summary
Research Summary
Adrenocortical carcinoma (ACC) is a very rare disease with a high risk of relapse after radical surgery. The efficacy of adjuvant mitotane treatment is suggested by a multicentre international study showing that post-operative mitotane treatment was associated with a significant reduction of the risk of relapse and death. However a randomised prospective trial is required to confirm these promising results and especially to assess whether mitotane treatment is efficacious in patients at low-intermediate risk of disease recurrence.
The primary objective is to compare the efficacy of mitotane treatment vs. observational follow-up only in prolonging survival without disease recurrence in patients with adrenocortical carcinoma at low or intermediate risk of recurrence after complete surgical resection of the tumour. Secondary objectives include assessing mitotane effect on prolonging total survival and time to disease recurrence, improvement in quality of life, as well as establishing potential treatment side effects and ascertaining patient characteristics that might have an impact on mitotane efficacy.
This will be an international, multicentre, randomised controlled study for patients with ACC after radical resection fulfilling the inclusion criteria and in whom no exclusion criteria are met. Patients will be randomly allocated to receive adjuvant therapy with mitotane or observational follow-up only. 4 years of recruitment and 2 years of follow-up are expected. The study is currently open in in Italy,France, Netherlands and Germany. The study will end approximately in the year 2015. The final report is expected in 2016. During the study period the participants will be undergoing regular assessment visits, including interviews, physical examination, blood tests and imaging to evaluate their clinical progress and avoid toxicity from mitotane.Summary of Results
Introduction
Deciding which treatments work best for patients almost always takes results from several trials. This summary shows the main results from the ADIUVO trial, other studies may provide new information or different results.
The trial was sponsored by the University of Turin, Italy and coordinated in the UK by the Cancer Research UK Clinical Trials Unit at the University of Birmingham. The research was approved and funded by Cancer Research UK and ENS@T (European Network for the Study of Adrenal Tumours).
We want to thank all the participants of this trial and their caregivers who helped the researchers learn more about whether treatment with Mitotane might improve the chances for the tumour not to come back in people with adrenocortical carcinoma. We hope this summary will help them understand and feel proud of their important role in medical research.
This summary is for information purposes only. If you need medical advice, please contact your doctor. If you participated in this trial and have questions about the results, please speak with a doctor or other staff member at the trial site.
Why was this research needed?
Before a treatment is available to all patients, researchers do clinical trials to get information about how well the treatment works and about how safe it is.
Adrenocortical carcinoma is a very rare disease with a high risk of the disease coming back even when the tumour has been completely removed by surgery. After surgery, if the results from examining the tumour tissue under the microscope, the pathology results, indicate a high likelihood of the tumour coming back, then patients are treated with Mitotane for at least two years, which has been shown to reduce the risk of tumour recurrence. However, if results suggest a low to intermediate risk of the tumour coming back then there is currently no clear guidance on the best treatment after surgery. Research is needed to find out whether patients with a low to intermediate risk tumour should also be treated with Mitotane or whether they should only be closely monitored.
What were the main questions studied?
The main question the researchers wanted to answer in this trial was, how well the risk of cancer coming back in patients judged to be at a low to intermediate risk of tumour recurrence could be reduced. This was measured by comparing the effect of treatment with Mitotane versus observation only in patients after their tumour had undergone pathology assessment. The researchers also examined whether Mitotane treatment had an effect on overall survival as compared to observation only.
The trial also wanted to find out how treatment or monitoring affected the patients quality of life and more about the side effects of Mitotane.Who participated in the trial?
Patients diagnosed with adrenocortical carcinoma with a low or intermediate risk of their cancer coming back after complete removal of their tumour by surgery.What treatments did the participants take?
ADIUVO was a randomised trial. The patients taking part were put into one of two groups randomly chosen by a computer. We use this method because sometimes we do not know which way of treating patients is best. To find out we need to compare different treatments. We put people into groups and give each group a different treatment. The results are then compared to see if one is better than the other.
The two treatment groups were:
• Treatment with Mitotane
• Observation onlyWhat happened during the trial?
Before deciding to take part in the trial, all the patients were provided with detailed information about it. They could also discuss it with their families and clinical team. This is called “informed consent.” Then the doctors and nurses asked the patients about their medical history and checked their health to make sure they could join the trial.
Patients had some tests done before taking part in the trial, these tests included:
• Assessment of the cancer
• Physical examination
• CT or MRI scan
• Electrocardiogram
• Blood tests
• Endocrine tests
• Record of adverse effects to treatment
• Pregnancy test (where applicable)
Patients attended a clinic visit every 3 months for 2 years, then every 6 months until year 5 and then every year.
At each clinic visit blood, urine samples and saliva (this was optional) were collected and patients were also asked to complete a questionnaire about the quality of their life.
After 6 months, a Positron Emission Tomography (PET) scan might have been done to monitor the patient’s progress if the study doctor thought that it was appropriate.
What were the results of the trial?
This is a summary of the main results from this study. These are the results from all the participants combined. The individual results of each participant might be different and are not in this summary.
The study started globally in 2008 and ended in December 2020. The study included 91 participants recruited in Italy, Germany, France, Croatia, Netherlands, Canada and United Kingdom.
o 45 patients had Mitotane
o 46 patients were on observation only
The results showed that patients with adrenocortical carcinoma at low-intermediate risk of recurrence after surgery are a minority amongst patients with adrenocortical carcinoma. The results also showed that they have a far better outcome than expected (in 75% of patients the cancer had not come back after 5 years) and they did not benefit significantly from having Mitotane.How has this trial helped patients and researchers?
The results of the ADIUVO study do not support routine use of Mitotane in this group of patients, who may therefore avoid a potentially toxic treatment. This is an important step towards personalised care of patients with adrenocortical carcinoma.Where can I learn more about the trial?
You can find more information about this study at the Cancer Research website:
https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbZ0oYz60WoglvPkqIfU1HPHTUfauCq2ZPvNtWjz0kGXSOCiSOfyPyipJY7AGHLby83CxCKkzl39Br4eiOAMc6C7iB2PZd7Dj1-2FjCYdDfeXGerz5sE23vEKXcW-2B5QFRW6P9MJDwJiVYPVII6JVpiY-2Be1RPr9K2yKfVT26U1bS-2FuFi8HEq_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YLbKW0i-2BLhvHJ8Fx3YVTFnP4AtQj7z7ZFHSsFOK4tMKOsGlM08K-2F-2F603tK03okho58TAqD3StmjZ-2BmuZO8HuwsfbOkFFneRdDfFWorlfixCzDexnpHA4JMFAU3FEE42AHt24OcExyEuPHtGarp18eDN6Esotq6wo42ok1QHFUy0Hw-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C673576423a1941ca978d08da488f115d%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637902076547275125%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=yupiX48br9Wecx3MeuDgN8nA%2FEbfzphwtNZpQMQdzUY%3D&reserved=0
If you have questions about this study, you can also contact the trial team by e-mail at adiuvo@trials.bham.ac.ukTrial information
Acronym ADIUVO
Full title of study:
ADIUVO: Efficacy of adjuvant mitotane treatment in prolonging recurrence-free survival in patients with adrenocortical carcinoma at low-intermediate risk of recurrence
Research sponsor: University of Turin, Italy
Name of Research Ethics Committee:
NRES Committee East Midlands - Northampton
Research Ethics Committee reference number: 13/EM/0144
Date study commenced globally: 2008
Date study commenced in UK: April 2014
Date study ended in the UK: January 2017 Date study ended globally: December 2020REC name
East Midlands - Leicester South Research Ethics Committee
REC reference
13/EM/0144
Date of REC Opinion
20 May 2013
REC opinion
Further Information Favourable Opinion