Gefitinib and Methotrexate (GEM) clinical trials: testing a new medical treatment for ectopic pregnancy

Gefitinib and Methotrexate (GEM) clinical trials: testing a new medical treatment for ectopic pregnancy

An ectopic pregnancy is a potentially life-threatening emergency that occurs when a pregnancy implants in the Fallopian tube. In our laboratory, we have identified a novel medical treatment for ectopic pregnancy that could replace surgery for many women. Working with friends abroad, we are performing clinical trials to see whether this could become the new standard medical treatment for ectopic pregnancy.

How does this new medical treatment work?

The growth of an ectopic pregnancy is extremely dependent on a protein called Epidermal Growth Factor Receptor (EGFR). We reasoned that a drug that blocks the function of EGFR would also stop the growth of an ectopic pregnancy.  In a series of laboratory studies we have found that combining an EGRF blocker called gefitinib with a traditional drug called methotrexate shows great promise as a new combination therapy for ectopic pregnancies.

The first patient trials with Gefitinib and Methotrexate (GEM1 and 2)

We partnered with Professor Andrew Horne at the University of Edinburgh to undertake the first patient trials of the gefitinib and methotrexate combination (GEM1 and 2).

In GEM1, we treated 12 women with small ectopic pregnancies with gefitinib tablets in addition to the traditional methotrexate injections. The combination appeared to be highly effective in clearing the ectopic pregnancy and performed better than treatment with methotrexate alone.

We next gave the combination treatment to eight women who had ‘extra-tubal ectopic pregnancies’. These are ectopic pregnancies that have implanted in unusual locations other than the Fallopian tube, such as a Caesarean section scar. These types of ectopic pregnancies can be particularly dangerous because they can be difficult to treat with surgery. All eight women were successfully cured without the need for surgery.

After these promising results, we tested the combination therapy in 28 women with larger ectopic pregnancies (GEM2). We were very encouraged to find that the majority of these women were able to to avoid surgery on our combination therapy.

The next step : A large scale clinical trial (GEM3)

GEM1 and GEM2 showed that combination therapy was safe and had great potential, but we needed a large scale clinical trial to definitively answer the question: "Is combination gefitinib and methotrexate therapy better than methotrexate alone for nonsurgical treatment of ectopic pregnancies?"

Led by Andrew Horne, our team recruited the help of the best researchers in the United Kingdom and have now commenced the GEM3 trial. This is a large randomised controlled study based in the UK that will involve over 300 patients in more than 50 hospitals. The main aim of GEM3 is to compare patient outcomes after treatment with gefitinib and methotrexate with outcomes after treatment with methotrexate alone. It will prove whether combination treatment is more effective for reducing the need for surgery than methotrexate alone.

If GEM3 fulfils its promise, then our gefitinib/ methotrexate combination may provide a safer and more reliable medical treatment for ectopic pregnancy, thus reducing the substantial risks and costs associated with surgery or medical treatment with methotrexate alone.

The GEM3 team

Chief Investigators

Professor Stephen Tong
Dr Monika Skubisz
Professor Andrew Horne (University of Edinburgh)
Ann Doust (University of Edinburgh)
Kirandeep Sunner (Birmingham Clinical Trial Unit)

There is a large network of study collaborators for GEM III, including colleagues from The University of Birmingham, University College London, University of Edinburgh, University of Aberdeen, and Adelaide University.

Who helped us make this happen?

We are very grateful to our supporters and those who have helped fund this work, including:

National Health and Medical Research Council
Monash Institute of Medical Research (Flagship Grant)
National Institute for Health Research (EME grant to fund GEM III)

Related external researchers

Professor Andrew Horne