Clinical trial NCT04593381: Efficacy and Safety of SBRT in Oligo-metastatic/Persistent/Recurrent Ovarian Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ovarian Neoplasms
Recurrent Ovarian Carcinoma
Oligometastatic Disease
Keywords: Oligometastasis
Stereotactic body radiotherapy
SBRT
SABR
Lead sponsor: Gemelli Molise Hospital
Sponsor class: OTHER
Collaborators: name: Fondazione Policlinico Universitario A. Gemelli, IRCCS
First posted: 2020-10-20
Enrollment: 376
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: Clinical complete response to SBRT by imaging
timeFrame: Assessment of Clinical complete response at six months
Secondary outcomes:
measure: 2-yr actuarial LC rate
timeFrame: 2 years
measure: 2-yr progression-free survival
timeFrame: 2 years
measure: 2-yr overall survival
timeFrame: 2 years
measure: treatment free interval
timeFrame: 2 years
measure: rate of toxicity
timeFrame: 2 years
measure: 2-yr actuarial late toxicity free survival
timeFrame: 2 years
Other outcomes:
measure: Radiomic clusters analysis
timeFrame: 2 years
measure: Breast cancer genes 1/2 (BRCA genes) characterization
timeFrame: 2 years
Locations:
city: Campobasso
country: Italy
facility: Responsible Research Hospital
state: CB
city: Biella
country: Italy
facility: S.C. di Radioterapia Oncologica-Azienda Sanitaria locale
city: Catania
country: Italy
facility: Azienda Ospedaliera "Cannizzaro"
city: Chieti
country: Italy
facility: Azienda sanitaria locale Lanciano Vasto Chieti
city: Lecce
country: Italy
facility: Ospedale Vito Fazzi
city: Milano
country: Italy
facility: Humanitas Clinical and Research Center-IRCCS
city: Milan
country: Italy
facility: Department of Radiation Oncology, IRCCS San Raffaele Scientific Institute
city: Reggio Emilia
country: Italy
facility: Azienda USL - IRCCS di Reggio Emilia
city: Roma
country: Italy
facility: Campus Biomedico
city: Roma
country: Italy
facility: Policlinico A. Gemelli, IRCCS
city: Roma
country: Italy
facility: Università La Sapienza
city: Roma
country: Italy
facility: Fatebenefratelli Isola Tiberina-Gemelli Isola,
city: Terni
country: Italy
facility: S Maria Hospital
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Radioterapia
Study officials:
affiliation: Radiotherapy Unit, Gemelli Molise
name: Gabriella Macchia
role: PRINCIPAL_INVESTIGATOR
References:
citation: Macchia G, Lazzari R, Colombo N, Laliscia C, Capelli G, D'Agostino GR, Deodato F, Maranzano E, Ippolito E, Ronchi S, Paiar F, Scorsetti M, Cilla S, Ingargiola R, Huscher A, Cerrotta AM, Fodor A, Vicenzi L, Russo D, Borghesi S, Perrucci E, Pignata S, Aristei C, Morganti AG, Scambia G, Valentini V, Jereczek-Fossa BA, Ferrandina G. A Large, Multicenter, Retrospective Study on Efficacy and Safety of Stereotactic Body Radiotherapy (SBRT) in Oligometastatic Ovarian Cancer (MITO RT1 Study): A Collaboration of MITO, AIRO GYN, and MaNGO Groups. Oncologist. 2020 Feb;25(2):e311-e320. doi: 10.1634/theoncologist.2019-0309. Epub 2019 Oct 10.
citation: Macchia G, Jereczek-Fossa BA, Lazzari R, Cerrotta A, Deodato F, Ippolito E, Aristei C, Gambacorta MA, Scambia G, Valentini V, Ferrandina G. Efficacy and safety of stereotactic body radiotherapy (SBRT) in oligometastatic/persistent/recurrent ovarian cancer: a prospective, multicenter phase II study (MITO-RT3/RAD). Int J Gynecol Cancer. 2022 Jul 4;32(7):939-943. doi: 10.1136/ijgc-2021-002709.