PATIENT
INFORMATION SHEET
GEM 3
Combination Gefitinib and Methotrexate
to treat Ectopic Pregnancy
You are being invited to take part in a clinical
trial called GEM 3. This trial is for women with
a diagnosis of an ectopic pregnancy who are
being treated with a drug called methotrexate
(MTX). Before you decide if you would like
to take part in the trial, it is important for
you to understand why the trial is being
done and what it will involve. Please
read the following information
carefully. Talk to others about the
study if you need help to decide
whether to take part. Ask us if
there is anything that is not
clear or if you would like more
information.
Thank you for taking the time to
consider taking part in this trial.
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Why are we doing this research?
An ectopic pregnancy occurs when the fertilised egg attaches itself somewhere other than
inside the womb, usually in the Fallopian tube. Sadly there is no chance of this pregnancy
surviving and if it is allowed to continue it could potentially be life threatening. If the ectopic
pregnancy is detected early enough it can be treated with a single dose of methotrexate
which stops the pregnancy developing. In some cases this single dose of methotrexate is
not successful and a further dose of methotrexate is required or surgery may be needed. A
more effective treatment is needed to reduce the need for repeat doses of methotrexate or
surgery. Previous studies using a drug called gefitinib in addition to methotrexate have shown
promising results. Gefitinib is a drug used in lung cancer patients. It has been shown to have
a blocking effect on the cells found in an ectopic pregnancy. These studies were in a small
number of women and we now need a larger group of women to prove that this treatment
reduces the need for repeat doses of methotrexate or the need for surgery. The combination
of methotrexate and gefitinib has been found to be safe and to have no serious side effects.
Why am I being invited to take part?
You are being asked to consider taking part because you have unfortunately been diagnosed
with an ectopic pregnancy which is being treated with methotrexate. We need 328
women to take part in our trial.
Do I have to take part?
No. Taking part is entirely voluntary and it is up to you to decide
whether to take part. Your treatment will not be affected in
any way if you decide not to take part or if you decide to
withdraw later on.
What will happen to me if I take part?
You will be given a copy of this information
sheet to keep. You will have as long as you
need to decide whether or not to take part.
If you decide to take part you will be asked
by a member of the research team to sign
a consent form. To confirm you are eligible
to take part, we will look at your blood and
ultrasound results with your permission.
We will ask you some questions about
your medical history and medications
you are taking. If a doctor confirms that
you can take part in the trial you will be
randomised to a treatment (please see
box to the right for more details).
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You will then be given seven tablets
(either gefitinib or placebo (dummy
drug)) and you will be asked to take
one a day for the next seven days.
No-one will know what treatment
you have been given as the tablets
look exactly the same.
You will be followed up as you
normally would at your hospital so
there are no extra visits. This usually
involves blood tests to measure
your hormone levels at around
days 4, 7, 11 and then weekly until
your hormone level is back to a prepregnancy level. After day 14, we will
repeat some blood tests just to make
sure that the drug combination has not
caused any harm to your liver or kidneys.
This will be with a routine blood test.
We will follow you up until your pregnancy
hormone blood results are back to a pre-pregnancy
level. After 3 months a member of the research team
will contact you by telephone to answer some questions
about your experience with the treatment and to find out when
your periods returned. This should only take about 5 minutes of your time.
We will ask your permission to access your medical records for 5 years following the study
to look and see if you have any pregnancies in the years following your ectopic pregnancy
and note what happened with these pregnancies. This will be done remotely looking at your
medical records.
If the treatment does not work and you need to have an operation to remove your ectopic
pregnancy we will ask permission to look at a small piece of the tissue that is routinely
removed during the operation to help us understand what effect the drugs have had.
A Double Blind Randomised Trial.
To find out what is the best way of treating patients we need to compare different
treatments. To do this we put people into groups and each group gets a different
treatment. The results are compared to see if one treatment is better. To make sure the
groups are the same to start with each patient is put into a group by chance (randomly).
This means you will have an equal chance of either being allocated to have methotrexate
and gefitinib or methotrexate and placebo (dummy drug). No-one will know what
medicine you have been given as the trial is blinded. This gives us fair results as no-one
can be biased towards the treatment they have received.
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Are there any side effects or risks involved?
Methotrexate and gefitinib have similar side effects, the most common of which are nausea,
diarrhoea and a skin rash. Other possible side effects include: vomiting, poor appetite, weight
loss, acne, dry skin, mouth ulcers, itch and a feeling of listlessness. An allergic reaction is
always a possibility when taking any medication. If you experience any shortness of breath,
wheezing, difficulty breathing, facial numbness, swelling or a rash, please notify a doctor as
soon as possible.
The most serious known side effect of gefitinib is the development of Interstitial Lung Disease
(ILD). This is a condition where the lungs are damaged by inflammation and become abnormally
thickened. If severe, it can stop the lungs working properly. ILD occurs in approximately three
in 1000 people taking the drug indefinitely (e.g. cancer patients who take this drug for life).
These figures have been calculated from 92,000 people taking gefitinib who already have
lung cancer. Therefore, it is possible that the lung cancer in combination with the drug may
have contributed to the development of ILD. All the evidence available would suggest that
seven doses of the gefitinib tablet should be safe, and the risk of developing ILD from this
exceedingly low. Besides having lung cancer, those most likely to develop ILD were those
older than 55 years, male, smokers and people of Japanese ethnicity. By excluding most of
these risk factors in our participants, including those with existing respiratory disease, and by
giving gefitinib for a maximum of seven days, we believe the risk of developing ILD is minimal.
The usual practice for anyone taking methotrexate alone for ectopic pregnancy is to avoid
getting pregnant (use contraception) and not to breastfeed for three months. This advice also
applies to gefitinib and methotrexate,
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What are the possible benefits of taking part?
We cannot promise the study will help you as an individual but the answers we get from this
study may help improve the treatment of women with ectopic pregnancy in the future.
What will happen if I do not want to carry on with the study?
You can withdraw from the study at any time without having to give a reason. With your
permission we will use any data obtained as a result of your participation. All data will be
anonymised (have no names on it).
What if there is a problem?
If you have a concern about any aspect of this study, you should ask to speak with your clinical
researchers who will do their best to answer your questions. If you remain unhappy and wish
to complain formally, you can do this through the NHS Complaints Procedure. Details at the
end of this information sheet.
Will my taking part in this study be kept confidential?
Yes. All information which is collected about you during the course of the research will be kept
strictly confidential similar to your medical records. With your permission, we will contact your
GP to inform them of your involvement in the trial. You will be allocated a unique number and
your responses to the questions will be held in a coded form in a secured central database
which is only accessible to the research team. Your responses will not be identified when the
results of the study are published. Your records may be viewed by the representatives of the
co-sponsors or regulatory authorities to check the research is conducted appropriately.
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What will happen to samples collected as part
of the research?
Any tissue samples collected from surgery will be analysed to
study the effect of the study drug(s). Analysis will take place in the
University of Edinburgh. If there are any leftover tissue samples,
with your permission, we would like to store these for use in future,
ethically approved research projects. The samples will not contain
any of your personal information and will only be identified by your
trial number.
What will happen to the results of the current
research study?
The results of this study will be published in medical journals, reports
and textbooks. You will not be identifiable in any publication or report.
Who is organising and funding the research?
The research is being organised by Professor Andrew Horne (Consultant
Gynaecologist) and the Birmingham Clinical Trials Unit. The study is
co-sponsored by the University of Edinburgh and NHS Lothian. The study is
funded by the NHS National Institute for Health Research.
Who has reviewed the study?
This study has been given a favourable ethical opinion for conduct by the NHS by
Scotland A Research Ethics Committee Rec Ref 16/SS/0014.
What if something goes wrong?
In the event that something does go wrong and you are harmed during the research and this
is due to someone’s negligence then you may have grounds for legal action for compensation
against the Sponsor Organisation (University of Edinburgh and NHS Lothian) and/or your
local NHS Trust but you may have to pay your legal costs. The normal National Health Service
complaints mechanisms will still be available to you (if appropriate).
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Contact details:
You may contact the clinical research team directly –
details below. If you require any further information
from a doctor who is not involved in this study you
can contact Dr Fiona Denison on 0131 242 1000.
FOR MORE INFORMATION CONTACT:
Thank you for reading this information sheet.
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