SOPRANO is a multi-centre, randomised phase II trial which aims to assess the impact of Stereotactic radiotherapy (SBRT) and continuing treatment with a PARP inhibitor (PARPi) for patients with oligometastatic or oligoprogressive ovarian, fallopian tube and primary peritoneal carcinoma. SOPRANO will also establish the feasibility and acceptability of delivering SBRT in this setting.
Oligometastases or oligoprogression of ovarian cancer while on a PARPi may occur due to a secondary sub-clonal mutation causing acquired resistance in a small volume of tumour rather than having global tumour resistance. Eradication of the resistant disease with stereotactic radiotherapy (SBRT) would enable continuation of the PARPi to maintain control of disease that has retained drug sensitivity and this has the potential to impact disease outcomes. For the purposes of this ovarian cancer trial, oligoprogression refers to the situation whereby 3 or less lesions of disease show evidence of progression. If there were previously other sites of disease, these remain in response or stable. Oligometastatic disease refers to the situation whereby complete response to treatment has been obtained and the disease relapse occurs that is limited in number and distribution (≤3 metastatic/recurrent lesions). SOPRANO will explore whether there is activity of SBRT and SBRT followed by niraparib in the case of oligometastatic or oligoprogression disease post prior PARPi in recurrent ovarian cancer. The trial will recruit patients with oligometastic or oligoprogressive ovarian cancer (≤3 sites/lesions) who have progressed on or following at least 6 months of treatment with PARP Inhibitor (PARPi). Patients will be randomised to one of two parallel non-comparative treatment cohorts: * Cohort 1: SBRT followed by niraparib * Cohort 2: SBRT alone In both cohorts, therapy will continue until disease progression deemed by the investigator to warrant a change in treatment, unacceptable toxicity, withdrawal of consent or if the investigator decides it is not in the best interest of the patient to continue. Adverse events, including toxicity from trial treatment will be collected and graded according to The National Cancer Institute (NCI) Common Terminology Criteria (CTC) Version 5.0 (http://ctep.cancer.gov/reporting/ctc.html). Participants will be asked to consent for future linkage with routinely collected health data via national registries to trace their eventual vital status and assess subsequent unexpected comorbidities. Assessment of disease by RECIST will be required 8 weekly following completion of SBRT for the first year and 12 weekly thereafter until disease progression meeting the primary endpoint.
Study Type
Niraparib used following SBRT treatment until disease progression
SBRT may be delivered using a specialist SBRT platform, such as CyberKnife or with a linear accelerator with SBRT capabilities.
Western General Hospital
Edinburgh, Scotland, United Kingdom
RECRUITINGThe Royal Marsden NHS Foundation Trust
Sutton, Surrey, United Kingdom
RECRUITINGUniversity College London Hospitals
London, UK, United Kingdom
Progression free survival
Progression free survival is defined as time from randomisation to evidence of progression of cancer at any site or death from any cause. Progression events should be imaging defined in all tumour types according to RECIST v1.1 criteria. Where SBRT specific consensus response assessment criteria exist for specific sites (e.g. spine), progression of SBRT treated lesions will be defined according to these guidelines.
Time frame: The primary timepoint of most interest for PFS is at six months after randomisation
Time to first subsequent systemic therapy
Time to first subsequent systemic therapy is defined as time from randomisation to commencing next systemic line of therapy or death from any cause (if this occurs before commencement of first subsequent treatment).
Time frame: Time to first subsequent systemic therapy assessed up to 2 years after randomisation.
Time to first subsequent anti-cancer therapy
Time to first subsequent anti-cancer therapy is defined as time from randomisation to commencing next line of therapy (local or systemic) or death from any cause (if this occurs before commencement of first subsequent treatment).
Time frame: Time to first subsequent anti-cancer therapy assessed up to 2 years after randomisation.
Overall survival
Overall survival (OS) defined as time from randomisation to death from any cause.
Time frame: The primary timepoint of interest for OS is at two years after randomisation.
Local control at site of SBRT
Local control at site of SBRT is defined as time from randomisation until radiological evidence of progression at the treated site and be measured on a lesion based analysis using RECIST v1.1 criteria
Time frame: Local control at site of SBRT assessed up to 2 years after randomisation.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
The Royal Marsden NHS Foundation Trust
London, United Kingdom
RECRUITINGThe Christie NHS Foundation Trust
Manchester, United Kingdom
RECRUITINGTime to 'Out of SBRT field' progression
Time to 'Out of SBRT field' progression is defined as time from randomisation until radiological evidence of progression outside of treated area(s) for SBRT treatment using RECIST v1.1.
Time frame: Time to 'Out of SBRT field' progression assessed up to 2 years after randomisation.
Clinician reported acute and late toxicity
Clinician reported acute and late toxicity will be graded using NCI CTCAE v5.0. Adverse events will be collected from start of treatment to disease progression (and 30 days post last dose of Niraparib for patients in cohort 1.
Time frame: Acute events are defined as those occurring up to 3 months follow up; late events are reported from 6 months post randomisation.
Quality of Life Assessments - FACT-O
Functional Assessment of Cancer Therapy - Ovarian (FACT-O): FACT-O is a self-report measure that assesses physical well-being, social/family well-being, emotional well-being, functional well-being and ovarian cancer-specific subscale. The higher the score, the better the QOL. Quality of Life will be collected at baseline prior to start of SBRT treatment, 4 weeks post SBRT treatment, 16, 24 and 48 weeks post randomisation and at disease progression. Changes from baseline at each time point will be compared within groups as well as between treatment cohorts.
Time frame: Quality of Life will be collected at baseline prior to start of SBRT treatment, 4 weeks post SBRT treatment, 16, 24 and 48 weeks post randomisation and at disease progression.
Quality of Life Assessments - EQ5D
EQ-5D-5L: The EQ-5D-5L is a self-assessed, health related, quality of life questionnaire. The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The higher the score, the better the QOL. Quality of Life will be collected at baseline prior to start of SBRT treatment, 4 weeks post SBRT treatment, 16, 24 and 48 weeks post randomisation and at disease progression. Changes from baseline at each time point will be compared within groups as well as between treatment cohorts.
Time frame: Quality of Life will be collected at baseline prior to start of SBRT treatment, 4 weeks post SBRT treatment, 16, 24 and 48 weeks post randomisation and at disease progression.
Feasibility of recruitment rate for the trial
Feasibility of recruitment is defined as the recruitment rate for the trial
Time frame: Recruitment is expected to be over 2.5 years
Proportion of patients receiving SBRT in the absence of new developing widespread disease
Proportion of patients receiving SBRT in the absence of new developing widespread disease, defined as greater than or equal to 4 metastatic sites, regional or distant, or a combination thereof.
Time frame: Proportion of patients receiving SBRT in the absence of new developing widespread disease assessed up to 2 years after randomisation.