Standard Treatment +/- SBRT in Solid Tumors Patients With Between 1 and 5 Bone-only Metastases (STEREO-OS)

Extracranial Stereotactic Body Radiation Therapy (SBRT) Added to Standard Treatment Versus Standard Treatment Alone in Solid Tumors Patients With Between 1 and 5 Bone-only Metastases

Bone metastases occur frequently during the evolution of solid tumors, either isolated or associated with visceral metastases. The incidence varies between 20 and 85% depending on the primary cancer. Breast, prostate, and lung cancers are responsible for 70% of bone metastases. Cancer with bone metastases compared to other metastatic sites is considered as associated with a better prognosis, particularly for breast and prostate cancer. Bone metastases may be present at diagnosis (synchronous metastasis) or appear at a later time (metachronous metastasis).

The concept of "oligometastases" was proposed in patients with about 3 up to 5 metastases (without restriction on the primary site) and associated with an intermediate prognosis. It was hypothesized that local treatment with curative intent, aiming at the few metastatic sites, would yield long-term survival probabilities, along with systemic therapies.

Long-term survivors have been reported after curative-intent treatment of metastasis in sarcoma and colorectal cancers with liver or lung metastasis. We chose to focus on bone metastasis because of their high incidence, their impact on the patient's quality of life and autonomy, and their accessibility to potentially curative radiotherapy.

The systemic treatment of metastatic cancer includes hormonal therapy (breast and prostate cancer), biologically-targeted drugs and chemotherapy (all cancers).

Stereotactic radiotherapy is a highly accurate technique was initially developed for performing the radiosurgery of brain tumors in patients for whom it was deemed be too difficult to proceed to classical excision surgery. In this process, a high total dose of radiation is delivered in a single fraction to a well-defined intra-cranial target. The concept of radiotherapy in stereotactic conditions was extended to one or several fractions delivered to small volumes primary tumors/ metastases in extra-cranial sites (Stereotactic Body RadioTherapy [SBRT]). At present, high control rates have been achieved for lung metastases. Similarly, very high local control rates have been reported in bone metastases after stereotactic radiotherapy.

In this protocol, our purpose is to demonstrate, via a randomized phase III trial, that high doses of radiotherapy, delivered in stereotactic conditions to the bone metastases (between 1 and 5 metastases) in solid tumor patients is able to improve the survival without progression.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Lung Cancer; Metastatic Breast Cancer; Bone Metastases; Metastatic Prostate Cancer
• Intervention / Treatment: Radiation: SBRT

• Study Type: Interventional
• Enrollment (Estimated): 196
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Saliha GHANEM, PhD; Phone Number: +33(0)1 80 50 12 98; Email: s-ghanem@unicancer.fr
• Study Contact Backup: Name: Assia LAMRANI-GHAOUTI, PhD; Email: a-lamrani-ghaouti@unicancer.fr

Study Locations

• France
  • Angers, France
    • Recruiting
    • ICO - Site Paul Papin
    • Contact: Stéphane SUPIOT, MD
  • Arras, France
    • Recruiting
    • Centre Marie Curie
    • Contact: Alexandre HENNI, MD
  • Arras, France
    • Active, not recruiting
    • Hôpital Privé Les Bonnettes
  • Avignon, France
    • Recruiting
    • Institut Sainte Catherine
    • Contact: Antoine ARNAUD, MD
  • Beuvry, France
    • Recruiting
    • centre Pierre Curie
    • Contact: Jean-Briac PREVOST, MD
  • Beuvry, France
    • Recruiting
    • Clinique Ambroise Pare
    • Contact: Jean-Briac PREVOST, MD
  • Bordeaux, France
    • Recruiting
    • Institut Bergonie
    • Contact: Adeline PETIT, MD
  • Bordeaux, France
    • Recruiting
    • Clinique Tivoli Ducos
    • Contact: Pauline REGNAULT DE LA MOTHE, MD
  • Chambray-lès-Tours, France
    • Recruiting
    • Pôle Leonard de Vinci
    • Contact: Pierre-Etienne CAILLEUX, MD
  • Chambéry, France
    • Recruiting
    • Hôpital Métropole Savoie
    • Contact: Philippe FOURNERET, MD
  • Creil, France
    • Recruiting
    • Centre Amethyst CROM
    • Contact: Andres HUERTAS, MD
  • Créteil, France
    • Recruiting
    • Hôpital Henri Mondor
    • Contact: Yazid BELKACEMI, MD
  • Dechy, France
    • Not yet recruiting
    • Centre Leonard de Vinci
    • Contact: Louis GRAS, MD
  • Dijon, France
    • Recruiting
    • Institut de Cancérologie de Bourgogne
    • Contact: Benjamin SCHIPMAN, MD
  • Dijon, France
    • Withdrawn
    • Centre Georges Francois Leclerc
  • Grenoble, France
    • Recruiting
    • CHU Grenoble
    • Contact: Carole IRIART, MD
  • Levallois Perret, France
    • Not yet recruiting
    • Centre de radiothérapie Hartmann
    • Contact: Alain TOLEDANO, MD
  • Lille, France
    • Recruiting
    • Centre OSCAR LAMBRET
    • Contact: David Pasquier, MD
  • Lille, France
    • Active, not recruiting
    • Hôpital Privé Le Bois
  • Lyon, France
    • Recruiting
    • Centre LEON BERARD
    • Contact: Marie-Pierre SUNYACH, MD
  • Marseille, France
    • Recruiting
    • Institut Paoli Calmettes
    • Contact: Laurence GONZAGUE-CASABIANCA, MD
  • Montpellier, France
    • Recruiting
    • Centre de Cancérologie du Grand Montpellier
    • Contact: Beatrice LAFFORGUE, MD
  • Nancy, France
    • Recruiting
    • Institut de Cancérologie de Lorraine
    • Contact: Jean-Francois FAIVRE, MD
  • Nantes, France
    • Recruiting
    • Institut de Cancérologie de l'Ouest
    • Contact: Stéphane SUPIOT, MD
  • Perpignan, France
    • Recruiting
    • Centre Catalan d'Oncologie
    • Contact: Sabine VIEILLOT, MD
  • Reims, France
    • Recruiting
    • Institut Jean Godinot
    • Contact: Philippe GUILBERT, MD
  • Rennes, France
    • Not yet recruiting
    • Centre Eugene Marquis
    • Contact: Renaud DE CREVOISIER, MD
  • Rouen, France
    • Recruiting
    • Centre Henri Becquerel
    • Contact: Sébastien THUREAU, MD
  • Saint-doulchard, France
    • Active, not recruiting
    • Centre d'oncologie et radiothérapie Saint-Jean
  • Saint-Étienne, France
    • Not yet recruiting
    • CHU Saint-Etienne
    • Contact: Omar JMOUR Omar, MD
  • Sarcelles, France
    • Active, not recruiting
    • GCS RISSA - Institut de cancérologie Paris Nord
  • Valence, France
    • Withdrawn
    • Centre Marie Curie
  • Valenciennes, France
    • Recruiting
    • Clinique des dentellières
    • Contact: Thomas LEROY, MD
  • Vannes, France
    • Not yet recruiting
    • Centre d'Oncologie Saint Yves
    • Contact: Osman EL KABBAJ, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients older than 18 years and younger than 75 years
2. Good general condition: WHO performance status ≤ 2
3. Patients with histological proof of breast, non-small cell lung, or prostate cancer Note: Histological proof can be done on the primitive tumour and/or adenopathy and/or metastatic site.
4. Absence of co-morbidity contra-indicating radio-chemotherapy or surgery
5. Primary tumor accessible to curative-intent treatment (surgery, chemoradiation…) for patients with synchronous metastases
6. Patients with between 1 and 5 synchronous or metachronous bone metastases as defined by NaF-PET or conventional SPECT-CT scan and spinal MRI (if necessary) within 6 weeks before randomization)
7. Bones metastases treatable by SBRT
8. Primary cancer considered to be controlled or accessible to curative-intent treatment (surgery, chemoradiation…) in case of locoregional recurrence for metachronous bone oligo-metastatic disease
9. Women of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 3 months following completion of therapy
10. Patients who have received the information sheet, dated and signed the informed consent form
11. Affiliated to the social security system

Exclusion Criteria:

1. Visceral metastases as defined by FDG-PET (F-Choline-PET or PSMA PET-CT for prostate cancer) and cerebral CT or MRI performed.
2. Previous systemic therapy for metastasis for patients with metachronous metastasis. Prostate and breast cancer patients remain eligible if hormonal treatment was initiated 6 months before enrollment
3. All bone metastasis requiring surgical treatment (spinal cord compression, fracture…)
4. More than 5 bone metastases as defined by NaF-PET or conventional SPECT-CT scan and spinal MRI (if spinal bone metastases on NaF-PET)
5. Previous cancer within the 5 years before inclusion (except basal cell carcinoma of the skin, in situ carcinoma of the uterine cervix)
6. Previous radiotherapy on bone metastasis (e.g: antalgic radiotherapy)
7. Patient enrolled in another therapeutic trial
8. Pregnant women or breast feeding mothers,
9. Hypersensitivity to the active substance (FDG and NaF or F-Choline or PSMA for prostate cancer) or to any of the excipients
10. Contraindication to MRI (in case of spinal metastases)
11. Patients deprived of liberty or placed under the authority of a tutor. Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. Patients unable to understand the purpose of the study (language, etc.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Systemic treatment + SBRT; Systemic treatment and SBRT to the bone metastases. Two SBRT schemes are allowed: 9 Gy x 3 fractions or 7 Gy x 5 fractions for axial and appendicular bones metastases. The choice is at the discretion of the investigator.	Radiation: SBRT; SBRT will be added to systemic (standard) treatment of bone metastases.
No Intervention: Systemic treatment; Palliative radiotherapy on bone metastases is allowed if necessary (pain, fracture, spinal cord compression…)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	To evaluate the impact of SBRT on Progression-Free Survival (PFS) at 1 year according to RECIST 1.1 and PERCIST 1.0 Criteria	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS at 2 and 3 years	Progression-Free Survival (PFS) at 2 and 3 years will be evaluated according to RECIST 1.1 and PERCIST	2 years and 3 years after treatment
Bone progression free survival at 1, 2 and 3 years	Distant bone progression at 2 and 3 years will be evaluated according to RECIST Criteria 1.1 and at 1 year according to RECIST Criteria 1.1 and PERCIST	1, 2 and 3 years after treatment
Local control at 1, 2 and 3 years	Local control will be evaluated at 1, 2 and 3 years according to RECIST Criteria 1.1 and PERCIST	1, 2 and 3 years after treatment
SBRT toxicities	according CTCAE 4.0 scale	1, 2 and 3 years after treatment
Patient's Quality of life	self-administered questionnaire	at baseline, 6 weeks after randomization, and 3 months, 6 months and 1, 2 and 3 years after treatment
Pain score	according to Numeric Scale related to pain medication	at baseline, once a week during 2 weeks and 6 weeks after randomization, and at 3 months, 6 months and 1, 2 and 3 years after treatment
Cost utility	QALYs (Quality-Adjusted Life Years) and ICERs (Incremental Cost-Effectiveness Ratios) calculation based on EQ-5D-3L questionnaire.	6 weeks after randomization
Cancer-specific survival	The length of time from the start of treatment for the disease until the death identified as being due to the specified cancer.	1, 2 and 3 years after treatment
Overall survival	The length of time from the start of treatment for the disease until patients are still alive.	1, 2 and 3 years after treatment

Collaborators and Investigators

• Sponsor: UNICANCER
• Collaborators: National Cancer Institute, France
• Investigators: Principal Investigator: Sebastien Thureau, MD, Centre Henri Becquerel; Principal Investigator: Jean-Christophe Faivre, MD, Institut de Cancérologie de Lorraine - Alexis Vautrin

Publications and helpful links

General Publications

• Thureau S, Marchesi V, Vieillard MH, Perrier L, Lisbona A, Leheurteur M, Tredaniel J, Culine S, Dubray B, Bonnet N, Asselain B, Salleron J, Faivre JC. Efficacy of extracranial stereotactic body radiation therapy (SBRT) added to standard treatment in patients with solid tumors (breast, prostate and non-small cell lung cancer) with up to 3 bone-only metastases: study protocol for a randomised phase III trial (STEREO-OS). BMC Cancer. 2021 Feb 4;21(1):117. doi: 10.1186/s12885-021-07828-2.

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2018
• Primary Completion (Estimated): January 24, 2026
• Study Completion (Estimated): July 24, 2027

Study Registration Dates

• First Submitted: April 28, 2017
• First Submitted That Met QC Criteria: May 3, 2017
• First Posted (Actual): May 8, 2017

Study Record Updates

• Last Update Posted (Estimated): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: solid tumors; SBRT; Bone-only metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: UC-0107/1603

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No