SBRT Alone or Followed by Niraparib for Oligometastases or Oligoprogression in Ovarian Cancer Following PARPi Therapy

NCT05990192 | Recruiting Phase 2 DMC

• 4 other identifiers: ICR-CTSU/2022/100822022-003175-42CCR572623/LO/0719
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Ovarian Cancer Recurrent

Keywords

Ovarian Cancer; Oligoprogressive; Oligometastatic; SBRT; PARP Inhibitor

Outcome Measures

Primary Outcomes (1)

• 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.

  The primary timepoint of most interest for PFS is at six months after randomisation

Secondary Outcomes (10)

• Time to first subsequent systemic therapy

  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 assessed up to 2 years after randomisation.

• Overall survival

  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 assessed up to 2 years after randomisation.

• Time to 'Out of SBRT field' progression

  Time to 'Out of SBRT field' progression assessed up to 2 years after randomisation.

Other Outcomes (3)

• Time to widespread metastatic disease

  Time to widespread metastatic disease assessed up to 2 years after randomisation.

• Time to second subsequent therapy

  Time to second subsequent therapy assessed up to 2 years after randomisation.

• Mechanisms of PARP inhibitor resistance, immune-mediated effects, radiosensitivity and toxicities

  From date of randomisation until date of progression meeting the primary endpoint or date of death from any cause, whichever came first, assessed up to 2 years

Study Arms (2)

SBRT followed by Niraparib

OTHER

SBRT treatment will commence within 7 days post randomisation and will be administered as detailed in the SOPRANO Radiotherapy Planning and Delivery Guidelines document. Doses will vary between 3 fractions over 5 days to 8 fractions over 19 days depending on the location of the lesions being treated. Niraparib treatment will start 4 weeks post completion of SBRT treatment and will continue daily until disease progression or other discontinuation criteria are met. Niraparib comes in oral tablet form and the starting dose will be 200mg per day (once a day) or 300mg per day (once a day) calculated by participant's weight and platelet count.

Drug: Niraparib oral capsule; Radiation: SBRT

SBRT alone

OTHER

SBRT treatment will commence within 7 days post randomisation and will be administered as detailed in the SOPRANO Radiotherapy Planning and Delivery Guidelines document. Doses will vary between 3 fractions over 5 days to 8 fractions over 19 days depending on the location of the lesions being treated.

Radiation: SBRT

Interventions

Niraparib oral capsule DRUG

Niraparib used following SBRT treatment until disease progression

Also known as: Zejula

SBRT followed by Niraparib

SBRT RADIATION

SBRT may be delivered using a specialist SBRT platform, such as CyberKnife or with a linear accelerator with SBRT capabilities.

Also known as: Stereotactic Body Radiotherapy

SBRT alone; SBRT followed by Niraparib

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years of age.
• Histologically confirmed epithelial ovarian, fallopian tube or primary peritoneal cancer.
• Radiological disease progression whilst on, or following, any prior PARP inhibitor therapy. The PARP inhibitor is required to have been the patient's last systemic therapy.
• Minimum duration of 6 months PARP inhibitor therapy as first line therapy or treatment for recurrent disease.
• ≤3 lesions of progressive disease.
• Each lesion to undergo SBRT \<4 cm axial diameter, and feasible for SBRT as discussed in the SOPRANO virtual MDT (vMDT) meeting.
• Measurable disease by RECIST criteria v1.1, which can be accurately assessed at baseline by CT or MRI. Patients with CA125 progression in the absence of measurable disease will NOT be eligible.
• No contra-indication to restarting a PARP inhibitor.
• Patients for whom surgery for recurrent disease is not planned.
• Adequate baseline organ function to allow SBRT to all relevant targets as deemed by the investigator.
• ECOG performance status of 0 or 1.
• Predicted life expectancy ≥ 6 months.
• Women of child-bearing potential who are confirmed NOT to be pregnant. This should be evidenced by a negative urine or serum pregnancy test within 72 hours prior to start of trial treatment. Patients will be considered to be not of child-bearing potential if they are:
• Post-menopausal -- defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments, OR women under 50 years old who have been amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments and have serum follicle- stimulating hormone (FSH), luteinizing hormone (LH) and plasma oestradiol levels in the post-menopausal range for the institution.
• Able to provide documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.

You may not qualify if:

• Co-morbidities which would preclude the safe use of SBRT.
• Progressing or newly diagnosed brain metastases identified at the time of trial entry, not amenable to radical surgery or stereotactic radiosurgery. Previously treated brain metastases (i.e. palliative radiotherapy or systemic therapy) which have remained clinically and radiologically stable for ≥ 6 months are permissible.
• Prior radiotherapy near the oligometastatic / oligoprogressive lesion precluding ablative SBRT. Suitability of lesions for ablative SBRT as part of the trial defined in Section 6.1 of this document and will be determined by the SOPRANO virtual MDT.
• Treatment with any other investigational medicinal product (IMP) within the 4 weeks prior to trial entry.
• Pregnant or lactating women.
• Women of childbearing age and potential who are not willing to use a highly effective contraceptive measure.
• Any unresolved toxicities from prior therapy should be no greater than CTCAE Grade 1 with the exception of Grade 2 alopecia or chemo-induced neuropathy at trial entry.
• Clinical/radiological evidence of bowel obstruction (e.g. hospitalisation) or symptoms of sub-acute bowel obstruction within 6 weeks prior to trial entry.
• Any other malignancy which has been active or treated within the past 3 years, with the exception of non-melanoma skin cancer. If prior treatment for another malignancy has taken place, then confirmation of ovarian/fallopian tube/peritoneal cancer progression is required e.g. biopsy, and discussion with the trial Chief Investigator and SBRT Lead
• Judgment by the Investigator that the patient is unsuitable to participate in the trial and/or the patient is unlikely to comply with trial procedures, restrictions and requirements.

Sponsors & Collaborators

• Institute of Cancer Research, United Kingdom: lead
• Royal Marsden NHS Foundation Trust: collaborator

Study Sites (5)

Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, SM2 5PT, United Kingdom

RECRUITING

University College London Hospitals

London, UK, NW1 2PG, United Kingdom

RECRUITING

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

niraparib; Radiosurgery

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Susana Banerjee

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lorna Smith

CONTACT

+44 0203 437 6647; soprano-icrctsu@icr.ac.uk

Laura Moretti

CONTACT

+44 0208 722 4153; soprano-icrctsu@icr.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2023
• First Posted: August 14, 2023
• Study Start: June 20, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (5)