Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/111749
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Type: Journal article
Title: Phase II single arm open label multicentre clinical trial to evaluate the efficacy and side effects of a combination of gefitinib and methotrexate to treat tubal ectopic pregnancies (GEM II): study protocol
Author: Horne, A.
Skubisz, M.
Doust, A.
Duncan, W.
Wallace, E.
Critchley, H.
Johns, T.
Norman, J.
Bhattacharya, S.
Mollison, J.
Rassmusen, M.
Tong, S.
Citation: BMJ Open, 2013; 3(7):e002902-1-e002902-5
Publisher: BMJ Publishing Group
Issue Date: 2013
ISSN: 2044-6055
2044-6055
Statement of
Responsibility: 
Andrew W Horne, Monika M Skubisz, Ann Doust, W Colin Duncan, Euan Wallace, Hilary O D Critchley, Terrance G Johns, Jane E Norman, Siladitya Bhattacharya, Jill Mollison, Michael Rassmusen, Stephen Tong
Abstract: Introduction: Tubal ectopic pregnancy (tEP) is the most common life-threatening condition in gynaecology. tEPs with pretreatment serum human chorionic gonadotrophin (hCG) levels <1000 IU/L respond well to outpatient medical treatment with intramuscular methotrexate (MTX). TEPs with hCG >1000 IU/L take a significant time to resolve with MTX and require multiple outpatient monitoring visits. Gefitinib is an orally active epidermal growth factor receptor (EGFR) antagonist. In preclinical studies, we found that EP implantation sites express high levels of EGFR and that gefitinib augments MTX-induced regression of pregnancy-like tissue. We performed a phase I toxicity study administering oral gefitinib and intramuscular MTX to 12 women with tEPs. The combination therapy did not cause significant toxicities and was well tolerated. We noted that combination therapy resolved the tEPs faster than MTX alone. We now describe the protocol of a larger single arm trial to estimate the efficacy and side effects of combination gefitinib and MTX to treat stable tEPs with hCG 1000–10 000 IU/L Methods and analysis: We propose to undertake a single-arm multicentre open label trial (in Edinburgh and Melbourne) and recruit 28 women with tEPs (pretreatment serum hCG 1000–10 000 IU/L). We intend to give a single dose of intramuscular MTX (50 mg/m2) and oral gefitinib (250 mg) daily for 7 days. Our primary outcome is the resolution of EP to non-pregnant hCG levels <15 IU/L without requirement of surgery. Our secondary outcomes are comparison of time to resolution against historical controls given MTX only, and safety and tolerability as determined by clinical/biochemical assessment. Ethics and dissemination: Ethical approval has been obtained from Scotland A Research Ethics Committee (MREC 11/AL/0350), Southern Health Human Research Ethics Committee B (HREC 11180B) and the Mercy Health Human Research Ethics Committee (R12/25). Data will be presented at international conferences and published in peer-reviewed journals.
Keywords: Gynaecology; Reproductive Medicine
Rights: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 3.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/3.0/
RMID: 0030083828
DOI: 10.1136/bmjopen-2013-002902
Grant ID: http://purl.org/au-research/grants/nhmrc/1008276
Appears in Collections:Medicine publications

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