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

NCT ID: NCT05990192

Last Updated: 2025-04-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

42 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-20

Study Completion Date

2027-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Ovarian Cancer Recurrent

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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SBRT followed by Niraparib

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.

Group Type OTHER

Niraparib oral capsule

Intervention Type DRUG

Niraparib used following SBRT treatment until disease progression

SBRT

Intervention Type RADIATION

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

SBRT alone

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.

Group Type OTHER

SBRT

Intervention Type RADIATION

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

Interventions

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Niraparib oral capsule

Niraparib used following SBRT treatment until disease progression

Intervention Type DRUG

SBRT

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

Intervention Type RADIATION

Other Intervention Names

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Zejula Stereotactic Body Radiotherapy

Eligibility Criteria

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Inclusion Criteria

1. Patients ≥ 18 years of age.
2. Histologically confirmed epithelial ovarian, fallopian tube or primary peritoneal cancer.
3. 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.
4. Minimum duration of 6 months PARP inhibitor therapy as first line therapy or treatment for recurrent disease.
5. ≤3 lesions of progressive disease.
6. Each lesion to undergo SBRT \<4 cm axial diameter, and feasible for SBRT as discussed in the SOPRANO virtual MDT (vMDT) meeting.
7. 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.
8. No contra-indication to restarting a PARP inhibitor.
9. Patients for whom surgery for recurrent disease is not planned.
10. Adequate baseline organ function to allow SBRT to all relevant targets as deemed by the investigator.
11. ECOG performance status of 0 or 1.
12. Predicted life expectancy ≥ 6 months.
13. 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:

1. 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.
2. Able to provide documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
3. Radiation or chemotherapy-induced oophorectomy or menopause with \> 1 year since last menses.
14. Willingness to commit to scheduled visits, treatments plans, laboratory tests and trial procedures.
15. Histological tissue specimen (tissue block or 8-10 unstained slides) must be available prior to commencing SBRT (specimen can be the sample at diagnosis or taken at relapse or progression). Otherwise, a biopsy must be carried out to obtain sufficient tissue for translational analyses.
16. Able to swallow, absorb and retain oral medication.
17. Able to provide written, informed consent.

Exclusion Criteria

1. Co-morbidities which would preclude the safe use of SBRT.
2. 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.
3. 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.
4. Treatment with any other investigational medicinal product (IMP) within the 4 weeks prior to trial entry.
5. Pregnant or lactating women.
6. Women of childbearing age and potential who are not willing to use a highly effective contraceptive measure.
7. 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.
8. Clinical/radiological evidence of bowel obstruction (e.g. hospitalisation) or symptoms of sub-acute bowel obstruction within 6 weeks prior to trial entry.
9. 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
10. 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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Royal Marsden NHS Foundation Trust

OTHER

Sponsor Role collaborator

Institute of Cancer Research, United Kingdom

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Susana Banerjee

Role: PRINCIPAL_INVESTIGATOR

Royal Marsden NHS Foundation Trust

Locations

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Western General Hospital

Edinburgh, Scotland, United Kingdom

Site Status RECRUITING

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom

Site Status RECRUITING

University College London Hospitals

London, UK, United Kingdom

Site Status RECRUITING

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status RECRUITING

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Lorna Smith

Role: CONTACT

+44 0203 437 6647

Laura Moretti

Role: CONTACT

+44 0208 722 4153

Facility Contacts

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Hannah McKinlay

Role: primary

0131 537 2444

Kylie Fitch

Role: primary

Janani Vijeyakumar

Role: primary

00 44 203 447 7832

Kylie Fitch

Role: primary

Jonathan Archer

Role: primary

Other Identifiers

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2022-003175-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CCR5726

Identifier Type: OTHER

Identifier Source: secondary_id

23/LO/0719

Identifier Type: OTHER

Identifier Source: secondary_id

ICR-CTSU/2022/10082

Identifier Type: -

Identifier Source: org_study_id

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