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 and completed three early phase trials.

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 then tested the combination therapy in 28 women with larger ectopic pregnancies (GEM2). We were very encouraged to find that most of the particiaants were successfully cured without needing surgery.

We also gave the drug combination to eight women who had 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 and are particularly dangerous. All eight women were successfully cured and managed to avoid surgery.

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

The early phase trials 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 our collaborator Professor Andrew Horne (University of Edinburgh), we have commenced an exciting large trial called GEM3. This is a large randomised placebo controlled trial based in the UK that aims to recruit 328 women with ectopic pregnancies. 

The study will examine whether the combination treatment compared to methotrexate alone will cure more ectopic pregnancies medically. It is well on its way, recruiting from over sixty hospitals in the United Kingdom and may be completed by the end of 2019.

If GEM3 returns a positive finding then it may mean the drug combination of  gefitinib and methotrexate combination could be a new way to treat ectopic pregnancy. It will allow far more women to avoid surgery and could cure ectopic pregnancies faster than methotrexate. 

It could become the standard of care in the way ectopic pregnancies are treated globally, making medical treatment safer, simpler, more accessible and cost-effective.

The GEM3 team

Chief Investigators for the GEM studies

Professor Stephen Tong

Dr Monika Skubisz

 Professor Andrew Horne, University of Edinburgh

Professor Colin Duncan, University of Edinburgh

Ann Doust, University of Edinburgh

There is a large network of study collaborators for GEM III, including colleagues from the University of Edinburgh and a large network of collaborators kindly recruiting participants across the United Kingdom.

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