Clinical trial NCT05990192: SBRT Alone or Followed by Niraparib for Oligometastases or Oligoprogression in Ovarian Cancer Following PARPi Therapy
Official title: SOPRANO: Stereotactic Radiotherapy Alone or Followed by Niraparib for Oligometastases or Oligoprogression in Ovarian Cancer Following PARP Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ovarian Cancer Recurrent
Keywords: Ovarian Cancer
Oligoprogressive
Oligometastatic
SBRT
PARP Inhibitor
Lead sponsor: Institute of Cancer Research, United Kingdom
Sponsor class: OTHER
Collaborators: name: Royal Marsden NHS Foundation Trust
First posted: 2023-08-14
Enrollment: 42
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

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.

Primary outcomes:
measure: Progression free survival
timeFrame: The primary timepoint of most interest for PFS is at six months after randomisation
Secondary outcomes:
measure: Time to first subsequent systemic therapy
timeFrame: Time to first subsequent systemic therapy assessed up to 2 years after randomisation.
measure: Time to first subsequent anti-cancer therapy
timeFrame: Time to first subsequent anti-cancer therapy assessed up to 2 years after randomisation.
measure: Overall survival
timeFrame: The primary timepoint of interest for OS is at two years after randomisation.
measure: Local control at site of SBRT
timeFrame: Local control at site of SBRT assessed up to 2 years after randomisation.
measure: Time to 'Out of SBRT field' progression
timeFrame: Time to 'Out of SBRT field' progression assessed up to 2 years after randomisation.
measure: Clinician reported acute and late toxicity
timeFrame: Acute events are defined as those occurring up to 3 months follow up; late events are reported from 6 months post randomisation.
measure: Quality of Life Assessments - FACT-O
timeFrame: 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.
measure: Quality of Life Assessments - EQ5D
timeFrame: 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.
measure: Feasibility of recruitment rate for the trial
timeFrame: Recruitment is expected to be over 2.5 years
measure: Proportion of patients receiving SBRT in the absence of new developing widespread disease
timeFrame: Proportion of patients receiving SBRT in the absence of new developing widespread disease assessed up to 2 years after randomisation.
Other outcomes:
measure: Time to widespread metastatic disease
timeFrame: Time to widespread metastatic disease assessed up to 2 years after randomisation.
measure: Time to second subsequent therapy
timeFrame: Time to second subsequent therapy assessed up to 2 years after randomisation.
measure: Mechanisms of PARP inhibitor resistance, immune-mediated effects, radiosensitivity and toxicities
timeFrame: 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
Locations:
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: London
country: United Kingdom
facility: University College London Hospitals
state: UK
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Susana Banerjee
role: PRINCIPAL_INVESTIGATOR
References: