798TiP - Stereotactic radiotherapy alone or followed by niraparib for oligometastases or oligoprogression in ovarian cancer following PARP inhibitor therapy: SOPRANO trial

Background

PARP Inhibitor (PARPi) maintenance therapy has transformed the management of both first line and platinum-sensitive recurrent ovarian cancer. Current practice for recurrent or progressive disease following a PARPi is initiation of the next line of systemic therapy. Retrospective series have reported the potential for radiotherapy to treat oligometastases (OMD) or oligoprogression (OPD) and continuation of a PARPi. OMD or OPD during treatment with a PARPi may occur due to acquired sub-clonal mutations causing resistance in a small volume of tumour rather than global tumour resistance. SOPRANO is a prospective, multicentre trial designed to assess the role of stereotactic radiotherapy (SBRT) to treat OMD or OPD and continuation of a PARPi to maintain control of disease that has retained drug sensitivity.

Trial design

SOPRANO is a phase II non-comparative, academic-sponsored clinical trial recruiting patients diagnosed with OMD or OPD ovarian cancer (≤3 OMD/OPD lesions). Main eligibility criteria include histologically confirmed epithelial ovarian, fallopian tube or primary peritoneal carcinoma with radiological OMD or OPD whilst receiving or following any prior PARPi therapy (minimum duration 6 months and must have been last systemic therapy). 42 participants will be randomised 1:1 to receive SBRT followed by niraparib (Cohort 1) or SBRT alone (Cohort 2). In both treatment cohorts, SBRT will be administered in accordance with the Stereotactic Ablative Radiotherapy (SABR) UK Consortium guidelines for each metastatic site. Participants in Cohort 1 will then receive niraparib once daily until disease progression. All participants will be followed up by RECIST v1.1 until disease progression. SBRT suitability will be reviewed by a virtual MDT and repeat SBRT is permitted for new lesions meeting the eligibility criteria (i.e. remains ≤3 sites). Samples will be collected for translational PARP inhibitor resistance research. The primary clinical endpoint is to determine whether the use of SBRT with or without niraparib increases progression free survival at 6 months. SOPRANO is planned to open at 6 UK centres commencing in Spring 2024.

Clinical trial identification

ISRCTN13282459; NCT05990192.

Editorial acknowledgement

Legal entity responsible for the study

Institute of Cancer Research.

Funding

GSK.

Disclosure

S. Banerjee: Financial Interests, Personal, Advisory Board: ImmunoGen, Mersana, MSD, Roche, AstraZeneca, GSK, Oncxerna, Shattuck Labs, Novartis, Epsilogen, Seagen, Eisai, Regeneron, Verastem, Myriad; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview, Novacure; Financial Interests, Personal, Stocks/Shares: PerciHealth; Financial Interests, Institutional, Research Grant: AstraZeneca, GSK; Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem; Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): AstraZeneca; Non-Financial Interests, Principal Investigator, Academic sponsored trial PI (MONITOR-UK): GSK; Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity; Non-Financial Interests, Leadership Role, Board Member: International Cancer Foundation (ICF). J. Bliss: Financial Interests, Institutional, Research Grant: AstraZeneca, Merck Sharp & Dohme, Puma Biotechnology, Clovis Oncology, Pfizer, Janssen-Cilag, Novartis, Eli Lilly, Roche. All other authors have declared no conflicts of interest.