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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

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 I...

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Autores principales: Horne, Andrew W, Skubisz, Monika M, Doust, Ann, Duncan, W Colin, Wallace, Euan, Critchley, Hilary O D, Johns, Terrance G, Norman, Jane E, Bhattacharya, Siladitya, Mollison, Jill, Rassmusen, Michael, Tong, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717468/
https://www.ncbi.nlm.nih.gov/pubmed/23872290
http://dx.doi.org/10.1136/bmjopen-2013-002902
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author Horne, Andrew W
Skubisz, Monika M
Doust, Ann
Duncan, W Colin
Wallace, Euan
Critchley, Hilary O D
Johns, Terrance G
Norman, Jane E
Bhattacharya, Siladitya
Mollison, Jill
Rassmusen, Michael
Tong, Stephen
author_facet Horne, Andrew W
Skubisz, Monika M
Doust, Ann
Duncan, W Colin
Wallace, Euan
Critchley, Hilary O D
Johns, Terrance G
Norman, Jane E
Bhattacharya, Siladitya
Mollison, Jill
Rassmusen, Michael
Tong, Stephen
author_sort Horne, Andrew W
collection PubMed
description 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/m(2)) 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. TRIAL REGISTRATION NUMBER: ACTRN12611001056987.
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spelling pubmed-37174682013-07-22 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 Horne, Andrew W Skubisz, Monika M Doust, Ann Duncan, W Colin Wallace, Euan Critchley, Hilary O D Johns, Terrance G Norman, Jane E Bhattacharya, Siladitya Mollison, Jill Rassmusen, Michael Tong, Stephen BMJ Open Obstetrics and Gynaecology 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/m(2)) 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. TRIAL REGISTRATION NUMBER: ACTRN12611001056987. BMJ Publishing Group 2013-07-18 /pmc/articles/PMC3717468/ /pubmed/23872290 http://dx.doi.org/10.1136/bmjopen-2013-002902 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions 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/
spellingShingle Obstetrics and Gynaecology
Horne, Andrew W
Skubisz, Monika M
Doust, Ann
Duncan, W Colin
Wallace, Euan
Critchley, Hilary O D
Johns, Terrance G
Norman, Jane E
Bhattacharya, Siladitya
Mollison, Jill
Rassmusen, Michael
Tong, Stephen
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Obstetrics and Gynaecology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3717468/
https://www.ncbi.nlm.nih.gov/pubmed/23872290
http://dx.doi.org/10.1136/bmjopen-2013-002902
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