Clinical trial NCT03143322: Standard Treatment +/- SBRT in Solid Tumors Patients With Between 1 and 5 Bone-only Metastases
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Metastatic Breast Cancer
Metastatic Lung Cancer
Metastatic Prostate Cancer
Bone Metastases
Keywords: Bone-only metastases
solid tumors
SBRT
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2017-05-08
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.).

Primary outcomes:
measure: Progression Free Survival
timeFrame: 1 year
Secondary outcomes:
measure: PFS at 2 and 3 years
timeFrame: 2 years and 3 years after treatment
measure: Bone progression free survival at 1, 2 and 3 years
timeFrame: 1, 2 and 3 years after treatment
measure: Local control at 1, 2 and 3 years
timeFrame: 1, 2 and 3 years after treatment
measure: Cancer-specific survival
timeFrame: 1, 2 and 3 years after treatment
measure: Overall survival
timeFrame: 1, 2 and 3 years after treatment
measure: SBRT toxicities
timeFrame: 1, 2 and 3 years after treatment
measure: Patient's Quality of life
timeFrame: at baseline, 6 weeks after randomization, and 3 months, 6 months and 1, 2 and 3 years after treatment
measure: Pain score
timeFrame: 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
measure: Cost utility
timeFrame: 6 weeks after randomization
Other outcomes:
Locations:
city: Angers
country: France
facility: ICO - Site Paul Papin
city: Arras
country: France
facility: Centre Marie Curie
city: Arras
country: France
facility: Hôpital Privé Les Bonnettes
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Beuvry
country: France
facility: Centre Pierre Curie
city: Beuvry
country: France
facility: Clinique Ambroise Pare
city: Bordeaux
country: France
facility: Clinique Tivoli Ducos
city: Bordeaux
country: France
facility: Institut Bergonié
city: Chambray-lès-Tours
country: France
facility: Pôle Leonard de Vinci
city: Chambéry
country: France
facility: Hôpital Métropole Savoie
city: Creil
country: France
facility: Centre Amethyst CROM
city: Créteil
country: France
facility: Hôpital Henri Mondor
city: Dechy
country: France
facility: Centre Léonard de Vinci
city: Dijon
country: France
facility: Institut de Cancérologie de Bourgogne
city: Grenoble
country: France
facility: Chu Grenoble
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lille
country: France
facility: Hôpital Privé Le Bois
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Centre de Cancérologie du Grand Montpellier
city: Nancy
country: France
facility: Institut de Cancérologie de Lorraine
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest
city: Perpignan
country: France
facility: Centre Catalan D'Oncologie
city: Reims
country: France
facility: Institut Jean Godinot
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-doulchard
country: France
facility: Centre d'oncologie et radiothérapie Saint-Jean
city: Sarcelles
country: France
facility: GCS RISSA - Institut de cancérologie Paris Nord
city: Valenciennes
country: France
facility: Clinique des dentellières
Study officials:
affiliation: Centre Henri Becquerel
name: Sebastien Thureau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut de Cancérologie de Lorraine - Alexis Vautrin
name: Jean-Christophe Faivre, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.