Efficacy and Safety of SBRT in Oligo-metastatic/Persistent/Recurrent Ovarian Cancer

Study Overview
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Brief Summary
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This is a prospective, multicenter, Phase II study aimed at defining the activity and safety of SBRT in MPR-OC. Clinical and imaging data as well as SBRT parameters would be analyzed with the aim to identify potential predictors of response to treatment and clinical outcome.

Detailed Description
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Stereotactic Body Radiotherapy (SBRT) represents the cutting edge within high conformal and modulated radiotherapy techniques; it can provide high local control (LC) for curative-intent of low burden metastatic, persistent and metastatic lesions in face of minimal acute and late toxicities. SBRT is amenable even in patients who had already been managed by radiotherapy. In addition, SBRT has been shown to be active in chemoresistant disease, and potentially able to mount immune response through the release of tumor neoantigens after cell killing, thus allowing to synergize with immunotherapeutic approaches. SBRT has been widely adopted in the clinical setting of oligometastatic/persistent/recurrent (MPR) disease (up to <5 lesions) in several malignancies including also ovarian cancer (OC); the recently published retrospective, multicenter Italian study (MITO-RT1) has confirmed the activity and safety of SBRT in MPR OC, thus providing a model able to predict the higher chance of complete response of tumor lesions to SBRT, and local control rate. The MITO-RT3/RAD trial is a prospective, Italian multicenter Phase II study aimed at evaluating the activity and safety of SBRT in MPR-OC patients. Clinical and imaging data, as well as SBRT technical parameters, would be analyzed with the aim to identify potential predictors of response to treatment and clinical outcome: in this context, additional insights into the tissue features of tumor lesions would be of clinical interest in the context of the personalized treatment, as testified by studies demonstrating that image-based quantitative features from pre-treatment imaging could predict clinical outcomes in several malignancies. Furthermore, given the crucial role played by the mutational status of BRCA 1/2 genes in this disease, the assessment of BRCA gene status was considered mandatory, thus representing inclusion criteria. The study will include patients with oligo-metastatic/persistent/recurrent lesions (MPR) from OC patients for which salvage surgery or other local therapies resulted not feasible, as per relative contraindication to further systemic therapy because of serious comorbidities, as per previous severe toxicity, unavailability of potentially active chemotherapy, or patient refusal of systemic therapy

Official Title
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Efficacy and Safety of Stereotactic Body Radiotherapy (SBRT in Oligo-metastatic/Persistent/Recurrent Ovarian Cancer (MPR-OC): a Prospective, Multicenter Phase II Study (MITO-RT3/RAD)

Conditions
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Oligometastatic Disease, Ovarian Neoplasms, Recurrent Ovarian Carcinoma

Intervention / Treatment
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* Radiation: Stereotactic body radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of ovarian cancer age >18 yrs, ECOG performance status 0-3, expected life expectancy >6 months, 1-5 synchronous lesions any site of disease, compulsory assessment of mutational status of BRCA1/2 genes (either germline or somatic), salvage surgery or other local therapies not feasible, relative contraindication to further systemic therapy because of serious comorbidities, previous severe systemic therapy toxicity unavailability of potentially active systemic therapy, patient refusal of systemic therapy, Re-treatment of lesions already treated with conventional external beam radiotherapy is allowed* Exclusion Criteria: mucinous OC, borderline ovarian tumors, non-epithelial OC, previous radiotherapy severe toxicity co-morbidities and functional impairment considered clinically precluding the safe use of SBRT, pregnancy any psychological, sociological, or geographical issue potentially hampering compliance with the study, lesion diameter larger than 5 centimeters

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBRT treatment<br>Intervention: Radiation: SBRT | Radiation: Stereotactic body radiotherapy<br>* All patients accrued will be treated with SBRT to all sites of active metastatic disease as per CT scan or PET/CT and/or MRI. A range of schedules and doses are provided, it is advised that the maximum dose that can be achieved whilst meeting the organs at risk planning constraints is prescribed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical complete response to SBRT by imaging | Radiologic response will be evaluated by morphological (contrast-enhanced CT scan and/or MRI) or functional imaging modalities (18F-fluorodeoxyglucose-PET) and classified according to the RECIST (version 1.1) or PERCIST criteria. | Assessment of Clinical complete response at six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-yr actuarial LC rate | progression of disease inside SBRT field on a per lesion basis | 2 years | 
| 2-yr progression-free survival | progression of disease out of SBRT field | 2 years | 
| 2-yr overall survival | patient survival | 2 years | 
| treatment free interval | time without any new treatment start after SBRT | 2 years | 
| rate of toxicity | SBRT acute and late toxicity rate | 2 years | 
| 2-yr actuarial late toxicity free survival | actuarial evaluation of late toxicity | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oligometastasis, Stereotactic body radiotherapy, SBRT, SABR