Bhattacharya, Siladitya

Critchley, Hilary O D

Doust, Ann

Duncan, W Colin Duncan

Horne, Andrew W.

Johns, Terence G

Mollison, Jill

Norman, Jane E

Rassmusen, Michael

Skubisz, Monika M

Tong, Stephen

Wallace, Euan

BMJ Open

PubMed

Horne, Andrew

Skubisz, Monika Michalina

Duncan, W

Critchley, Hilary

Johns, Terrance

Norman, Jane

Monash University Research Repository

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 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

Horne, AW

Skubisz, MM

Doust, A

Duncan, WC

Wallace, E

Critchley, HOD

Johns, TG

Norman, JE

Bhattacharya, S

Mollison, J

Rassmusen, M

Tong, S

University of Melbourne Institutional Repository

Aberdeen University Research

Phase II single arm open label multicentre clinical trial to evaluate the efficacy and side effects of combination gefitinib and methotrexate to treat ectopic pregnancies (GEM II) : study protocol

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

Crossref

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 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 level

Skubisz, Monika M.

Duncan, W. Colin

Critchley, Hilary O. D.

Johns, Terrance G.

Norman, Jane E.

Explore Bristol Research

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)

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 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.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 Ton

Horne, A.

Skubisz, M.

Doust, A.

Duncan, W.

Wallace, E.

Critchley, H.

Johns, T.

Norman, J.

Bhattacharya, S.

Mollison, J.

Rassmusen, M.

Tong, S.

Adelaide Research &amp; Scholarship

Edinburgh Research Explorer

https://digital.library.adelaide.edu.au/dspace/bitstream/2440/111749/2/hdl_111749.pdf

Phase II single arm open label multicentre clinical trial to evaluate the efficacy and side effects of combination gefitinib and methotrexate to treat ectopic pregnancies (GEM II) : study protocol

Abstract

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Monash University Research Repository

University of Melbourne Institutional Repository

Aberdeen University Research

Crossref

Explore Bristol Research

Adelaide Research & Scholarship

Edinburgh Research Explorer

Phase II single arm open label multicentre clinical trial to evaluate the efficacy and side effects of combination gefitinib and methotrexate to treat ectopic pregnancies (GEM II) : study protocol

Abstract

Similar works

Full text

Available Versions

Monash University Research Repository

University of Melbourne Institutional Repository

Aberdeen University Research

Crossref

Explore Bristol Research

Adelaide Research &amp; Scholarship

Edinburgh Research Explorer

Adelaide Research & Scholarship