An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor

Martin Gore; Allan Hackshaw; William E Brady; Richard T Penson; Richard Zaino; W Glenn McCluggage; Raji Ganesan; Nafisa Wilkinson; Timothy Perren; Ana Montes; Jeffrey Summers; Rosemary Lord; Graham Dark; Gordon Rustin; Melanie Mackean; Nicholas Reed; Sean Kehoe; Michael Frumovitz; Helen Christensen; Amanda Feeney; Jonathan Ledermann; David M Gershenson

doi:10.1016/j.ygyno.2019.03.256

An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor

Martin Gore, Allan Hackshaw, William E Brady, Richard T Penson, Richard Zaino, W Glenn McCluggage, Raji Ganesan, Nafisa Wilkinson, Timothy Perren, Ana Montes, Jeffrey Summers, Rosemary Lord, Graham Dark, Gordon Rustin, Melanie Mackean, Nicholas Reed, Sean Kehoe, Michael Frumovitz, Helen Christensen, Amanda FeeneyJonathan Ledermann, David M Gershenson

Cancer and Genomic Sciences

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

Abstract

OBJECTIVES: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer.

METHODS: We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL).

RESULTS: The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3-4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms.

CONCLUSION: mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782.

Original language	English
Pages (from-to)	541-548
Number of pages	8
Journal	Gynecologic oncology
Volume	153
Issue number	3
DOIs	https://doi.org/10.1016/j.ygyno.2019.03.256
Publication status	Published - Jun 2019

Keywords

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols/adverse effects
Bevacizumab/administration & dosage
Capecitabine/administration & dosage
Carboplatin/administration & dosage
Carcinoma, Ovarian Epithelial/drug therapy
Female
Follow-Up Studies
Humans
Internationality
Middle Aged
Neoplasm Recurrence, Local/drug therapy
Neoplasms, Cystic, Mucinous, and Serous/drug therapy
Ovarian Neoplasms/drug therapy
Oxaliplatin/administration & dosage
Paclitaxel/administration & dosage
Progression-Free Survival
Quality of Life
Response Evaluation Criteria in Solid Tumors
Survival Rate
Young Adult

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Gore, M., Hackshaw, A., Brady, W. E., Penson, R. T., Zaino, R., McCluggage, W. G., Ganesan, R., Wilkinson, N., Perren, T., Montes, A., Summers, J., Lord, R., Dark, G., Rustin, G., Mackean, M., Reed, N., Kehoe, S., Frumovitz, M., Christensen, H., ... Gershenson, D. M. (2019). An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor. Gynecologic oncology, 153(3), 541-548. https://doi.org/10.1016/j.ygyno.2019.03.256

@article{03cc59f06944442fbd34570a0cb0319a,

title = "An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor",

abstract = "OBJECTIVES: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer.METHODS: We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL).RESULTS: The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3-4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms.CONCLUSION: mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782.",

keywords = "Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Bevacizumab/administration & dosage, Capecitabine/administration & dosage, Carboplatin/administration & dosage, Carcinoma, Ovarian Epithelial/drug therapy, Female, Follow-Up Studies, Humans, Internationality, Middle Aged, Neoplasm Recurrence, Local/drug therapy, Neoplasms, Cystic, Mucinous, and Serous/drug therapy, Ovarian Neoplasms/drug therapy, Oxaliplatin/administration & dosage, Paclitaxel/administration & dosage, Progression-Free Survival, Quality of Life, Response Evaluation Criteria in Solid Tumors, Survival Rate, Young Adult",

author = "Martin Gore and Allan Hackshaw and Brady, {William E} and Penson, {Richard T} and Richard Zaino and McCluggage, {W Glenn} and Raji Ganesan and Nafisa Wilkinson and Timothy Perren and Ana Montes and Jeffrey Summers and Rosemary Lord and Graham Dark and Gordon Rustin and Melanie Mackean and Nicholas Reed and Sean Kehoe and Michael Frumovitz and Helen Christensen and Amanda Feeney and Jonathan Ledermann and Gershenson, {David M}",

year = "2019",

month = jun,

doi = "10.1016/j.ygyno.2019.03.256",

language = "English",

volume = "153",

pages = "541--548",

journal = "Gynecologic oncology",

issn = "0090-8258",

publisher = "Elsevier",

number = "3",

}

Gore, M, Hackshaw, A, Brady, WE, Penson, RT, Zaino, R, McCluggage, WG, Ganesan, R, Wilkinson, N, Perren, T, Montes, A, Summers, J, Lord, R, Dark, G, Rustin, G, Mackean, M, Reed, N, Kehoe, S, Frumovitz, M, Christensen, H, Feeney, A, Ledermann, J & Gershenson, DM 2019, 'An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor', Gynecologic oncology, vol. 153, no. 3, pp. 541-548. https://doi.org/10.1016/j.ygyno.2019.03.256

An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor. / Gore, Martin; Hackshaw, Allan; Brady, William E et al.
In: Gynecologic oncology, Vol. 153, No. 3, 06.2019, p. 541-548.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up

T2 - and experience of conducting a clinical trial in a rare gynecological tumor

AU - Gore, Martin

AU - Hackshaw, Allan

AU - Brady, William E

AU - Penson, Richard T

AU - Zaino, Richard

AU - McCluggage, W Glenn

AU - Ganesan, Raji

AU - Wilkinson, Nafisa

AU - Perren, Timothy

AU - Montes, Ana

AU - Summers, Jeffrey

AU - Lord, Rosemary

AU - Dark, Graham

AU - Rustin, Gordon

AU - Mackean, Melanie

AU - Reed, Nicholas

AU - Kehoe, Sean

AU - Frumovitz, Michael

AU - Christensen, Helen

AU - Feeney, Amanda

AU - Ledermann, Jonathan

AU - Gershenson, David M

PY - 2019/6

Y1 - 2019/6

N2 - OBJECTIVES: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer.METHODS: We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL).RESULTS: The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3-4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms.CONCLUSION: mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782.

AB - OBJECTIVES: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer.METHODS: We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL).RESULTS: The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3-4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms.CONCLUSION: mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Bevacizumab/administration & dosage

KW - Capecitabine/administration & dosage

KW - Carboplatin/administration & dosage

KW - Carcinoma, Ovarian Epithelial/drug therapy

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Internationality

KW - Middle Aged

KW - Neoplasm Recurrence, Local/drug therapy

KW - Neoplasms, Cystic, Mucinous, and Serous/drug therapy

KW - Ovarian Neoplasms/drug therapy

KW - Oxaliplatin/administration & dosage

KW - Paclitaxel/administration & dosage

KW - Progression-Free Survival

KW - Quality of Life

KW - Response Evaluation Criteria in Solid Tumors

KW - Survival Rate

KW - Young Adult

U2 - 10.1016/j.ygyno.2019.03.256

DO - 10.1016/j.ygyno.2019.03.256

M3 - Article

C2 - 31005287

SN - 0090-8258

VL - 153

SP - 541

EP - 548

JO - Gynecologic oncology

JF - Gynecologic oncology

IS - 3

ER -