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

Ovarian Neoplasms Clinical Trial

— MITO-RT3/RAD  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04593381
• Other study ID #: CE 07-14-2020
• Status: Recruiting
• Phase: N/A
• Start date: March 1, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: September 2022
• Source: Gemelli Molise Hospital
• Contact: Gabriella Macchia, MD
• Phone: 0874 312259
• Email: macchiagabriella[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Oligometastatic Disease
• Ovarian Neoplasms
• Recurrence
• Recurrent Ovarian Carcinoma

Intervention

Radiation:
• Stereotactic body radiotherapy
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.

Locations

Country	Name	City	State
Italy	S.C. di Radioterapia Oncologica-Azienda Sanitaria locale	Biella
Italy	Gemelli Molise Hospital	Campobasso	CB
Italy	Azienda sanitaria locale Lanciano Vasto Chieti	Chieti
Italy	Department of Radiation Oncology, IRCCS San Raffaele Scientific Institute	Milan
Italy	Campus Biomedico	Roma
Italy	Policlinico A. Gemelli, IRCCS	Roma
Italy	Università La Sapienza	Roma
Italy	Azienda Sanitaria Universitaria Friuli Centrale (ASU FC) - SOC Radioterapia	Udine

Sponsors (2)

Lead Sponsor	Collaborator
Gemelli Molise Hospital	Fondazione Policlinico Universitario A. Gemelli, IRCCS

Country where clinical trial is conducted

Italy, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Radiomic clusters analysis	Investigation of radiomic features for clustering analysis to predict response according to other histological and clinical parameters	2 years
Other	Breast cancer genes 1/2 (BRCA genes) characterization	Investigation of the mutational status of BRCA 1/2 genes in this disease	2 years
Primary	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	2-yr actuarial LC rate	progression of disease inside SBRT field on a per lesion basis	2 years
Secondary	2-yr progression-free survival	progression of disease out of SBRT field	2 years
Secondary	2-yr overall survival	patient survival	2 years
Secondary	treatment free interval	time without any new treatment start after SBRT	2 years
Secondary	rate of toxicity	SBRT acute and late toxicity rate	2 years
Secondary	2-yr actuarial late toxicity free survival	actuarial evaluation of late toxicity	2 years