Clinical trial NCT02800551: Clinical Trial Comparing Dose-intensified SBRT With Conventional Radiation Therapy for Spinal Metastases
Official title: Dose-intensified Image-guided Fractionated Stereotactic Body Radiation Therapy for Painful Spinal Metastases Versus Conventional Radiation Therapy: a Randomised Controlled Trial (DOSIS RCT)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Spinal Metastasis
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2016-06-15
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will compare pain (primary end-point) and local metastatic tumor control (secondary end-point) after dose-intensified image-guided fractionated stereotactic body radiation therapy (SBRT) for painful mass-type spinal metastases versus conventional radiation therapy.

Detailed description: Rationale: Radiation therapy is an effective palliative treatment for painful spinal metastases. A sub-group of patients with mass-type spinal metastases, a factor associated with poor local metastasis control, require treatment optimization ensuring durable pain control and metastatic tumor control.

Proposed solution: To intensify (escalate) radiation dose using simultaneous integrated boost with image-guided hypofractionated SBRT for painful mass-type spinal metastases in a randomized controlled trial. Two experimental fractionation regimes will be tested in the study depending on presence or absence of epidural involvement. Dose intensification is expected to achieve long-term pain control and long-term palliation as well as long-term local metastatic tumor control without adding toxicity as compared to conventional fractionation regimes with conventional radiation therapy.

The study will be carried out as multinational, multicentre phase II clinical controlled trial enrolling patients with painful mass-type spinal metastases who are eligible for radiation therapy without surgery. This study additionally includes a prospective observational arm for patients not eligible for randomisation who are treated in analogy to arm A of the randomised arm.

Eligibility criteria: Inclusion Criteria:

* Established histological diagnosis of a malignant primary or metastatic tumor;
* Histologically, radiologically or scintigraphically proven spinal metastasis;
* Pain in the affected spinal region or free of pain under pain medication;
* Age ≥18 years old;
* Karnofsky performance status ≥60%;
* Written informed consent.

Exclusion Criteria:

* Modified Bauer Score \< 2;
* No-mass-type metastatic lesion, defined as a 3D space-occupying lesion visible on CT and/or MR;
* "Radiosensitive" histology of the primary tumor, e.g., lymphoma, small-cell lung cancer, multiple myeloma, germ cell tumors;
* Progressive neurological symptoms/deficit;
* More than 3 affected vertebrae in one target site;
* More than 2 treatment sites;
* Spinal Instability Neoplastic Score (SINS) 13 - 18, i.e., unstable;
* Unable to tolerate treatment (unable to lie flat and immobilized);
* Previous radiotherapy of the region at the level of the affected vertebrae;
* Previous radionuclide therapy within 30 days before stereotactic body radiation therapy;
* Previous surgery (stabilization) of the affected vertebrae;
* Contraindications for MR scanning, e.g., pacemakers;
* Patients with allergy to contrast agents used in computer tomography (CT) and magnetic resonance (MR) imaging or patients who cannot be premedicated to use contrast agent;
* Pregnant or lactating women;
* Women of child bearing potential or sexually active males not willing to use effective contraception while on treatment and 3 months after the end of treatment;
* Mental conditions rendering the patient unable to understand the nature, scope, and possible consequences of the study;
* Patient unlikely to comply with protocol, i.e. uncooperative attitude, inability to return for follow-up visits, and unlikely to complete the study.

Primary outcomes:
measure: Pain response - improvement by ≥ 2 points on the pain Visual Analogue Scale at 6 months post-treatment at the treatment site
timeFrame: 6 months
Secondary outcomes:
measure: Local metastasis control
timeFrame: up to 2 years
measure: Overall survival
timeFrame: up to 2 years
measure: Cancer-specific survival
timeFrame: up to 2 years
measure: Quality-of-life (QoL)
timeFrame: Day 1 and last day of treatment (usually day5 if Radiotherapy is delivered in 5 fractions, and day 12 if Radiotherapy is delivered in 10 fractions); months 1, 3, 6, 9, 12, 18 and 24
measure: Epidural spinal cord compression
timeFrame: up to 2 years
measure: Acute and late toxicity
timeFrame: Acute toxicity: up to 3 months; late toxicity: from 3 months up to 24 months
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich, Klinik für Radio-Onkologie
Study officials:
affiliation: Universitätsspital Zürich
name: Matthias Guckenberger, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: