Clinical trial NCT06078813: Spine SABR - Dose-escalated Stereotactic Ablative Body Radiotherapy (SABR) for Solid Tumour Spine Metastases
Official title: Spine SABR - Dose-escalated Stereotactic Ablative Body Radiotherapy (SABR) for Solid Tumour Spine Metastases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor Spine Metastases
Keywords: Solid Tumor Spine Metastases
Dose-Escalated Stereotactic Ablative Body Radiotherapy
Lead sponsor: Cancer Trials Ireland
Sponsor class: NETWORK
First posted: 2023-10-12
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Treatment will consist of image guided dose escalated SABR using a simultaneous integrated boost (SIB) delivered in two fractions adhering to organ at risk dose-volume histogram constraints. There will be three dose levels delivered to the Planning Target Volume_1 (PTV_1) in each treatment arm as follows: 28 Gy (14 Gy per fraction), 30 Gy (15 Gy per fraction) and 32 Gy (16 Gy per fraction). A lower dose of 20 Gy (10 Gy per fraction) will be delivered to the PTV_2 which will be defined according to international consensus guidelines (Cox et al., 2012). The dose to PTV_2 will remain the same through all dose levels. All doses are prescribed to the target volume.
Primary purpose: TREATMENT

Brief summary: This study will look at treatment for patients that have already been diagnosed with cancer, but develop a new tumor(s) in the spine. Patients who are not recommended for surgery are usually treated with 5-10 sessions of radiotherapy to manage symptoms. For patients with a longer life expectancy (\>6 months), it is better to give a higher dose of treatment to potentially improve the duration of pain relief, cancer control and potentially survival. Higher doses of radiotherapy, however, may also cause worse toxicity and side effects. This study will look at delivering higher doses of radiation in 2 sessions rather than 5-10, using a more modern, targeted technique called image-guided Stereotactic Ablative Body Radiotherapy (SABR). This method requires special equipment and expertise compared to the traditional radiotherapy and this has limited availability in Ireland. This study aims to find out the highest dose that is safe to be given to patients and carefully examine the side effects. These results will help create national and international guidelines to benefit all cancer patients. Patients will be monitored closely during treatment and for 2 years afterwards. Patients have been involved in developing the treatment protocol and the patient information leaflet. Patients will also be asked to fill in quality of life (QOL) questionnaires at certain timepoints during the study. It is anticipated that this study will support the delivery of high quality SABR to all cancer patients in Ireland, resulting in potentially better quality of life, symptom and tumor control.


Eligibility criteria: Inclusion Criteria:

1. Written informed consent obtained prior to any study-related procedures
2. ≥ 18 years of age
3. Life expectancy \> 6 months
4. ECOG (Eastern Cooperative Oncology Group) performance status (PS) 0-2
5. Histological diagnosis of malignant primary disease (excluding haematologic, seminomatous or small cell subtype)
6. Diagnosis of oligometastatic disease (OMD) or oligoprogressive disease (OPD) defined as:

   1. OMD where there are 1 to 5 metastatic lesions, with a controlled primary tumor being optional, but where all metastatic sites must be safely treatable (can be synchronous or metachronous to primary tumor diagnosis) with curative intent OR
   2. OPD with 1 to 5 lesions progressing on a background of widespread but stable metastatic disease OR
   3. Systemic therapy-induced OMD where there are 1 to 5 persistent lesions after systemic therapy, all safely treatable with SABR
7. Single spinal level from C1 to L5 to be treated for the purpose of the study (co-existing lesion(s) on non-consecutive spinal level(s) may receive RT at Investigator discretion, if deemed unlikely to interfere with study treatment and assessment of outcomes).
8. Stable spine assessed by Spinal Instability Neoplastic Score (SINS) (SINS 0-6, or SINS 7-12 and not for surgical intervention).
9. Bilsky Grade 0-1a (i.e. minimal (epidural impingement, without deformation of thecal sac) or no epidural disease) as confirmed by Radiation Oncologist
10. Able to lie flat in the treatment position for radiotherapy for up to 60 minutes
11. Females of childbearing potential must not be pregnant or lactating, and must be prepared to take adequate contraception methods during treatment. Males whose female partners are of childbearing potential must be prepared to take adequate contraception methods during treatment. Examples of effective contraception methods are a condom or a diaphragm with spermicidal jelly, or oral, injectable or implanted birth control

Exclusion Criteria:

1. Previous radiotherapy or surgery to the proposed SABR treatment site which is likely to interfere with treatment or assessment of outcomes (for radiotherapy, this includes prior thoracic radiotherapy to the lung or oesophagus which would result in overlap of fields if a T spine lesion will be treated)
2. Patients with symptomatic spinal cord compression or cauda equina syndrome, resulting in bony compression or epidural compression of the spinal cord or cauda equine, respectively
3. Patients with syndromes or conditions associated with increased radiosensitivity
4. Patients with radiosensitive histologies, e.g. myeloma or lymphoma
5. Contraindication to MRI, e.g. MRI-incompatible personal pacemaker in situ
6. Patients with pre-existing osteoporotic fractures of the spine
7. Prior treatment with any radionuclide within 30 days prior to registration
8. Patients who have received chemotherapy within 1 week prior to administration of protocol RT or who are expected/planned to receive chemotherapy during RT or within 1 week after completing protocol RT
9. Uncontrolled intercurrent illness that is likely to interfere with treatment or assessment of outcomes, or psychiatric illness/social situations that would limit compliance with study requirements
10. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study, or if it is felt by the research / medical team that the patient may not be able to comply with the protocol and follow-up schedule due to psychological, familial, sociological or geographical conditions
11. Significant or progressive neurological deficit such that emergency surgery or radiation required

Primary outcomes:
measure: The establishment of the MTD of 2-fraction spine SABR in patients with oligometastatic or oligoprogressive solid tumor metastases of the spine, by the number of patients experiencing DLTs within six months after treatment.
timeFrame: From start of treatment to 6 months post treatment
Secondary outcomes:
measure: Estimate local progression-free survival at 1 and 2 years post-treatment, using Magnetic Resonance Imaging (MRI).
timeFrame: Up to 2 years post treatment
measure: Estimate 6-month, 1-year and 2-year post-treatment overall survival rates.
timeFrame: Up to 2 years post treatment
measure: Estimate the pain flare incidence 1 week post-treatment (i.e. 1 week after 2nd SABR fraction) using the Numeric Pain Rating Scale (NPRS) 0-10.
timeFrame: 1 week post treatment
measure: Pain score at radiation site (treated per study protocol) at 4 weeks, 3 months, 6 months, 1 year and 2 years post-treatment, using the NPRS.
timeFrame: Up to 2 years post-treatment
measure: Acute toxicity profiles of ≥Grade 2 toxicities at 1- and 4-weeks post treatment, and at 3 months post-treatment using NCI CTCAE V5
timeFrame: Up to 3 months post-treatment
measure: Late toxicity profiles of ≥Grade 2 toxicities and DLTs at 6, 9, 12, 15, 18 and 24 months post-treatment using NCI CTCAE V5.
timeFrame: Up to 2 years post-treatment
measure: Estimates of time to onset of ≥ Grade 2 and ≥ Grade 3 acute toxicities.
timeFrame: Up to 3 months post-treatment
Other outcomes:
measure: Estimate median time to onset of post-SABR ≥ Grade 2 VCF and rates of post-SABR ≥ Grade 2 VCF at 1 and 2 years. VCF is assessed via MRI.
timeFrame: Up to 2 years post-treatment
measure: Type of intervention (surgery or kyphoplasty) in the setting of post-SABR VCF at 1 and 2 years.
timeFrame: The type of intervention (surgery or kyphoplasty) in the setting of post-SABR VCF at 1 and 2 years will be described.
measure: QoL outcomes at 6-months and 1-year post SABR (compared to baseline) using EORTC QLQ-BM22 (EORTC Quality of Life Questionnaire for Patients with Bone Metastases (22 questions)).
timeFrame: Up to 1 year post-treatment
Locations:
city: Cork
country: Ireland
facility: Bon Secours/UPMC
city: Dublin
country: Ireland
facility: St Luke's Radiation Oncology Network (SLRON) at Beaumont Hospital
city: Dublin
country: Ireland
facility: Beacon Hospital
Study officials:
affiliation: Cancer Trials Ireland/ St Luke's Radiation Oncology Network
name: Clare Faul, MBBS
role: PRINCIPAL_INVESTIGATOR
References: