Using SBRT and Niraparib for Ovarian Cancer with Limited Progression

SOPRANO: Stereotactic Radiotherapy Alone or Followed by Niraparib for Oligometastases or Oligoprogression in Ovarian Cancer Following PARP Inhibitor Therapy

This study is testing if combining a type of targeted radiation therapy with a cancer medication can help women with advanced ovarian cancer that has only spread a little bit feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Institute of Cancer Research, United Kingdom (Academic / other)
• Drugs / interventions: chemotherapy, Radiation
• Locations: 5 sites (Edinburgh, Scotland and 4 other locations)
• Trial ID: NCT05990192 on ClinicalTrials.gov

What this trial studies

The SOPRANO trial is a multi-centre, randomised phase II trial designed to evaluate the effectiveness of Stereotactic Radiotherapy (SBRT) alone or followed by the PARP inhibitor Niraparib in patients with oligometastatic or oligoprogressive ovarian cancer. The study focuses on patients who have shown disease progression while on PARP inhibitor therapy and have a limited number of lesions. Participants will be randomly assigned to receive either SBRT followed by Niraparib or SBRT alone, with the aim of maintaining disease control and improving outcomes. The trial will also assess the feasibility and acceptability of administering SBRT in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed ovarian, fallopian tube, or primary peritoneal cancer who have oligometastatic or oligoprogressive disease after at least 6 months of PARP inhibitor therapy.

Not a fit: Patients with more than three lesions of disease progression or those for whom surgery for recurrent disease is planned may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve disease control and extend the effectiveness of PARP inhibitors in patients with recurrent ovarian cancer.

How similar studies have performed: While the specific combination of SBRT and Niraparib in this context is novel, previous studies have shown promising results with SBRT in managing oligometastatic disease.

Eligibility criteria

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.

Where this trial is running

Edinburgh, Scotland and 4 other locations

• Western General Hospital — Edinburgh, Scotland, United Kingdom (Recruiting)
• The Royal Marsden NHS Foundation Trust — Sutton, Surrey, United Kingdom (Recruiting)
• University College London Hospitals — London, UK, United Kingdom (Recruiting)
• The Royal Marsden NHS Foundation Trust — London, United Kingdom (Recruiting)
• The Christie NHS Foundation Trust — Manchester, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Susana Banerjee — Royal Marsden NHS Foundation Trust
• Study coordinator: Lorna Smith

Conditions Ovarian Cancer Recurrent; Ovarian Cancer; Oligoprogressive; Oligometastatic; SBRT; PARP Inhibitor