Clinical trial NCT04043156: RAdiotherapy for Metastatic Spinal Cord Compression with Increased Radiation DosES
Official title: RAdiotherapy for Metastatic Spinal Cord Compression with Increased Radiation DosES
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Spinal Cord Compression Due to Metastasis to Spine
Keywords: spinal cord compression, radiotherapy
Lead sponsor: University Hospital Schleswig-Holstein
Sponsor class: OTHER
First posted: 2019-08-02
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single arm study compared with a historical cohort.
Primary purpose: TREATMENT

Brief summary: This clinical study aims to investigate whether high-precision radiotherapy, as supposed, leads to a better control of the irradiated spinal cord metastases when compared to conventional radiotherapy. This means that a progression or recurrence of motor deficits (weakness) of the legs following radiotherapy can be avoided more effectively. Furthermore, the high-precision radiotherapy will be compared to the conventional radiotherapy with respect to pain relief, motor function/ability to walk, quality of life, side effects and survival.

Detailed description: The aim of this single-arm study is to show that high-precision radiotherapy (RT) with 18x2.33 Gy in 3.5 weeks results in significantly better local progression free survival (LPFS) of metastatic spinal cord compression (MSCC) when compared to conventional RT with 10x3 Gy in 2 weeks. If such superiority could be shown, 18x2.33 Gy could be recommended, at least for those patients with favourable survival prognoses, since an in-field recurrence of MSCC in the irradiated part of the spine is generally very difficult to treat.

For this investigation the newly prospectively collected data will be compared with a historical cohort collected up to the time of data analysis.

The recruitment of all 65 patients (62 patients + 5% for potential drop-outs) is planned to be completed within 21 months. The follow-up period will be 12 months. This equals a total running time for the study of 33 months.

In accordance with a previous study assessing local control of MSCC, the following patient characteristics will be recorded to allow adequate comparison with the historical control group:

* Age
* Gender
* Type of primary tumor (breast cancer vs. prostate cancer vs. myeloma/ lymphoma vs. lung cancer vs. other tumors)
* Interval from tumor diagnosis to MSCC (≤15 months vs. \>15 months)
* Number of involved vertebrae (1-2 vs. ≥3)
* Other bone metastases at the time of RT (no vs. yes)
* Visceral metastases at the time of RT (no vs. yes)
* Time developing motor deficits prior to RT (1-7 days vs. 8-14 days vs. \>14 days)
* Ambulatory status prior to RT (no vs. yes)
* Eastern Cooperative Oncology Group (ECOG) performance score (0-2 vs- 3-4)
* Indication for decompressive surgery of affected spinal areas

The patients of this study who received high-precision RT with 18x2.33 Gy for MSCC will be compared to a historical control group of patients with a favorable survival prognosis who were treated with 10x3 Gy of conventional RT. The historical control group will include data from 235 patients qualifying for the comparison with the prospectively collected data.

Data for the historical control group will be collected from an already existing anonymized database with previous study data documented in the European Union.

To be eligible for control group, patients fulfilling the same inclusion criteria and exclusion criteria as defined in the prospective study are considered. Furthermore, to be consistent with efficacy analysis of the study, patients of the historical control group must have received at least 80% of the planned RT dose.

Propensity score techniques will be applied to reduce confounding due to differences between the historical control group and the prospective trial data.

Eligibility criteria: Inclusion Criteria:

1. Motor deficits of the lower extremities resulting from MSCC, which have persisted for no longer than 30 days
2. Confirmation of diagnosis by MR-imaging (computed tomography \[CT\] allowed)
3. Age 18 years or older
4. Written informed consent
5. Favorable survival prognosis (defined as 36-45 points on the survival score)
6. Capacity of the patient to contract

Exclusion Criteria:

1. Previous RT or surgery of the spinal areas affected by MSCC
2. Symptomatic brain tumor or symptomatic brain metastases
3. Metastases of the cervical spine only
4. Other severe neurological disorders
5. Pregnancy, Lactation
6. Clear indication for spinal surgery

Primary outcomes:
measure: Local progression-free survival at 12 months following RT.
timeFrame: For each patient 12 months after the end of RT.
Secondary outcomes:
measure: Change in motor function/ability to walk
timeFrame: Assessment directly and at 1, 3, 6, 9 and 12 months after RT.
measure: Change in quality of life
timeFrame: Evaluation directly and at 1, 3, 6, 9 and 12 months after RT
measure: Change in vertebral pain
timeFrame: Evaluation directly and at 1, 3, 6, 9 and 12 months after RT
measure: Overall survival
timeFrame: Evaluation directly and at 1, 3, 6, 9 and 12 months after RT
measure: Local progression-free survival
timeFrame: Additional evaluation directly and 1, 3, 6 and 9 months after RT
measure: Occurence of toxicity
timeFrame: Evaluation during RT and directly, 1, 3, 6, 9 and 12 months after RT
measure: Change in sensory function
timeFrame: Evaluation during RT and directly, 1, 3, 6, 9 and 12 months after RT
measure: Chance in sphincter dysfunction
timeFrame: Evaluation during RT and directly, 1, 3, 6, 9 and 12 months after RT
Other outcomes:
Locations:
city: Lubeck Hansestadt
country: Germany
facility: Department of Radiation Oncology, University of Lübeck and University Medical Center Schleswig-Holstein, Ratzeburger Allee 160, 23562 Lübeck, Germany
Study officials:
affiliation: Dep. of Radiation Oncology, Univ. of Lübeck and Univ. Medical Center S-H
name: Dirk Rades, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rades D, Hansen O, Jensen LH, Dziggel L, Staackmann C, Doemer C, Cacicedo J, Conde-Moreno AJ, Segedin B, Ciervide-Jurio R, Rubio-Rodriguez C, Perez-Romasanta LA, Alvarez-Gracia A, Dennis K, Ferrer-Albiach C, Navarro-Martin A, Lopez-Campos F, Jankarashvili N, Janssen S, Olbrich D, Hollander NH. Radiotherapy for metastatic spinal cord compression with increased radiation doses (RAMSES-01): a prospective multicenter study. BMC Cancer. 2019 Nov 29;19(1):1163. doi: 10.1186/s12885-019-6390-x.