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Clinical trial
Olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in patients with recurrent ovarian cancer: phase III randomized, open-label MITO 35b study, a project of the MITO-MANGO groups
  1. Clorinda Schettino1,
  2. Lucia Musacchio2,
  3. Michele Bartoletti3,
  4. Paolo Chiodini4,
  5. Laura Arenare1,
  6. Gustavo Baldassarre5,
  7. Daniela Califano6,
  8. Ettore Capoluongo7,8,
  9. Maria Paola Costi9,
  10. Maurizio D'Incalci10,11,
  11. Sergio Marchini11,
  12. Delia Mezzanzanica12,
  13. Nicola Normanno13,
  14. Stefania Scala6,
  15. Stefano Greggi14,
  16. Francesco Perrone1 and
  17. Sandro Pignata15
  1. 1Clinical Trial Unit, Istituto Nazionale Tumori, IRCCS, “Fondazione Giovanni Pascale”, Naples, Italy
  2. 2Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, Rome, Italy
  3. 3Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
  4. 4Department of Mental Health and Public Medicine, Section of Statistics, Università degli Studi della Campania Luigi Vanvitelli, Naples, Italy
  5. 5Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy
  6. 6Microenvironment Molecular Targets Unit, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Naples, Italy
  7. 7Department of Molecular Medicine and Medical Biotechnology, Università degli Studi di Napoli Federico II, Naples, Italy
  8. 8Azienda Ospedaliera per L'Emergenza, Cannizzaro, Catania, Italy
  9. 9Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
  10. 10Laboratory of Molecular Pharmacology, Group of Cancer Pharmacology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
  11. 11Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
  12. 12Molecular Therapies Unit, Department of Research, Istituto Nazionale dei Tumori IRCCS, Milan, Italy
  13. 13Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione Giovanni Pascale", Naples, Florida, USA
  14. 14Gynecologic Oncology Surgery, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy
  15. 15Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS “Fondazione Giovanni Pascale”, Naples, Italy, 80131
  1. Correspondence to Professor Sandro Pignata, Gynaecological Oncology, National Cancer Institute Napels, Naples, Italy; s.pignata{at}istitutotumori.na.it

Abstract

Background Poly (ADP-ribose) polymerase inhibitors have transformed the management landscape for patients with ovarian cancer, demonstrating remarkable improvements in progression-free survival and overall survival. Unfortunately, most relapses are due to an acquired mechanism of resistance to these agents. We hypothesize that secondary cytoreductive surgery, removing resistant clones, might help to overcome the development of resistance to poly (ADP-ribose) polymerase inhibitors, prolonging their therapeutic effect.

Primary Objective To determine the efficacy of olaparib beyond progression compared with standard platinum-based chemotherapy in patients with recurrent ovarian cancer progressed during or after poly (ADP-ribose) polymerase inhibitor maintenance therapy after secondary cytoreductive surgery.

Study Hypothesis Olaparib administered beyond progression is more effective in increasing progression-free survival and progression-free survival 2 compared with second-line platinum-based chemotherapy in patients after secondary cytoreductive surgery.

Trial Design Phase III, randomized, open-label, multicenter trial. Eligible patients will be randomized in a 1:1 ratio to receive olaparib or platinum-based chemotherapy of the investigator’s choice.

Major Eligibility Criteria Eligible patients must have high-grade serous or endometrioid ovarian cancer progressed during or after first-line poly (ADP-ribose) polymerase inhibitor maintenance therapy and must have undergone secondary cytoreductive surgery.

Primary Endpoint The dual primary endpoints will include progression-free survival and progression-free survival 2. Progression-free survival is defined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as the time between randomization and progression or death from any cause. Progression-free survival 2 is defined by the investigator using RECIST version 1.1 as the time frame from randomization to the second progression or death from any cause after subsequent treatment.

Sample Size Approximately 200 patients will be enrolled in this study.

Estimated Dates for Completing Accrual and Presenting Results Enrollment will be completed in 2024. Results will be presented in 2026.

Trial Registration EudraCT 2021-000245-41 NCT05255471

  • ovarian cancer
  • BRCA1 protein
  • BRCA2 protein

Data availability statement

There are no data in this work.

https://doi.org/10.1136/ijgc-2022-003435

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    Data availability statement

    There are no data in this work.

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    Footnotes

    • Twitter @Barto_Med, @fperrone62

    • Contributors SP is responsible for study design. LM, MB, and CS are responsible for drafting the manuscript. PC and LA are responsible for statistical analysis and data interpretation. All authors are responsible for the acquisition and quality control of the data. SP, FP, and SG are responsible for the critical revision of the manuscript for important intellectual content. SP is guarantor.

    • Funding The study is funded by AstraZeneca.

    • Competing interests FP reports honoraria for educational and advisory activity from Incyte, GSK, Eli Lilly, Ipsen, Astellas, AstraZeneca, Roche, BMS, Bayer, Clovis, Pierre Fabre and grants for clinical trials to his institution from Roche, AstraZeneca, Pfizer, MSD, Bayer, Incyte Taiho, Janssen, Exelixis, Ailenor, Daiichi Sankyo. SP reports honoraria from AstraZeneca, MSD, Roche, Pfizer, Clovis, GSK, Pharmamar and research funding from MSD, Roche, AstraZeneca and Pfizer. NN reports personal financial interests (speaker’s fee and/or advisory boards): MSD, Qiagen, Bayer, Biocartis, Illumina, Incyte, Roche, BMS, MERCK, Thermofisher, AstraZeneca, Sanofi, Eli Lilly, Novartis and institutional financial interests (financial support to research projects) from MERCK, Thermofisher, QIAGEN, Roche, AstraZeneca, Biocartis, Illumina, Blueprint.

    • Provenance and peer review Commissioned; internally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.