PROSSPER
Research type
Research Study
Full title
PROgesterone as a Steroid SParing agent against oEdema occurring with secondary bRain cancers
IRAS ID
1004104
Contact name
Chris Twelves
Contact email
Sponsor organisation
Public Health Scotland
Eudract number
2021-003171-34
ISRCTN Number
ISRCTN16167828
Research summary
Summary of Research
Patients that have brain tumours often have swelling in their brain caused by the tumour. This swelling can cause headaches, sickness and sometimes seizures (epileptic fits). The normal way to treat this swelling is to use a medicine called dexamethasone. Unfortunately, dexamethasone has side effects including change in mood, sleep problems & weight gain. Patients with brain tumours can take dexamethasone for long periods & these side effects can lower their quality of life.
Progesterone is a naturally occurring chemical in the body and has been used in contraceptive (pregnancy prevention) tablets for several decades and has few side effects.
Progesterone has been used in animal models to look at head injury and has been shown to reduce swelling. In animal models, brain tumours do not cause as much swelling as in humans. The first thing we need to find out if the dose (amount) of progesterone that will provide the most effective level in the patient’s blood. This will be Stage 1.
Once confirmed, we then need to make sure that patients with brain tumours do not have any unexpected side effects. This part of the study will involve finding out about patients’ quality of life. This will be Stage 2.
If the Prossper study is successful, then a larger trial will be needed to compare two groups of patients – those taking dexamethasone and those taking a lower dose of dexamethasone plus progesterone.The two stages are:
Stage 1: 6-12 patients will be enrolled at Leeds Hospital. These patients will take the current treatment, dexamethasone, and at two timepoints, patients will be given the study drug - progesterone. This stage is 10 days.Stage 2: 36 patients will be recruited to take part at either Leeds or Liverpool Hospital. These patients will all be prescribed the current treatment, dexamethasone. In addition, 18 of these patients will be randomly selected to receive progesterone. The other 18 will receive a dummy tablet - placebo. This stage is 22 days.
Summary of Results
"Recruitment to Stage 1 was halted on 06/12/2023 due to the planned closure of Public Health Scotland (PHS) CTU and withdrawal of sponsor responsibilities. At this time six patients had been recruited as per planned target accrual, of whom four completed the study with paired pharmacokinetic data.
A redesigned Stage 2 protocol was submitted to NIHR on 19/02/2024 for approval in principle for a costed extension including a change in sponsor to Glasgow and delivery with the Glasgow Oncology CTU. NIHR rejected this proposal on 28/03/2024 stating that their decision was primarily based on the extent of changes to the study design, despite initial discussions with NIHR having suggested this was a viable approach, and the associated increase in cost. NIHR requested that the study be closed down.
A request was then submitted for NIHR agreement to submit a different, abbreviated proposal for a no-cost extension to submit a protocol amendment to change sponsor to University of Leeds to recruit the remaining evaluable patients required to complete Stage 1. NIHR agreed to submission of options appraisal for consideration, which was submitted to NIHR on 17/04/2024. NIHR rejected this proposal on 19/04/2024 and requested that the study be closed down.
Chief Investigators (CIs) requested a meeting at that time to discuss this decision directly with NIHR EME Programme Director (PD); it was not, however, feasible for NIHR to host the meeting until 10th July 2024. The CIs delivered a presentation to EME PD and Consultant Advisor who confirmed that they were supportive in that they recognised the clinical need for the research question, and the value in completing Stage 1, but raised concerns related to potential delays for a Deed of Novation to change study sponsor and stated they required to discuss further internally.
Final confirmation was then received from EME PD on 16/07/2024 that due to a number of ongoing concerns, the final decision was for the NIHR/ PHS contract for PROSSPER to terminate on the current planned date of 31/07/2024."REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
21/EE/0262
Date of REC Opinion
23 Dec 2021
REC opinion
Further Information Favourable Opinion