Clinical Trial Comparing Dose-intensified SBRT With Conventional Radiation Therapy for Spinal Metastases (DOSIS RCT)

University of Zurich (UZH)

Status and phase: Active, not recruiting; Phase 2

Conditions: Spinal Metastasis

Treatments: Radiation: External 3-dimensional conformal radiotherapy (3D-CRT); Radiation: dose-intensified image-guided SBRT using simultaneous integrated boost

Study type: Interventional

Funder types: Other

Identifiers

NCT02800551

DOSIS RCT

Details and patient eligibility

About

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.

Full 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.

Enrollment: 219 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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219 participants in 3 patient groups

SBRT (Arm A)

Experimental group

Description:

dose-intensified image-guided SBRT using simultaneous integrated boost: * in the case of no epidural involvement: 40 Gy and 20 Gy in 5 fractions to the high-dose and conventional-dose target volume, respectively. * In the case epidural involvement: 48.5 Gy and 30 Gy in 10 fractions to the high-dose and conventional-dose target volume, respectively.

Treatment:

Radiation: dose-intensified image-guided SBRT using simultaneous integrated boost

Conventional Radiation Therapy (Arm B)

Active Comparator group

Description:

External 3-dimensional conformal radiotherapy (3D-CRT): Homogeneous irradiation of the affected vertebra delivering either * 20 Gy in 5 fractions or * 30 Gy in 10 fractions.

Treatment:

Radiation: External 3-dimensional conformal radiotherapy (3D-CRT)

SBRT (prospective observational)

Experimental group

Description:

Patients eligible for the prospective observational arm will be treated according to the investigational arm (arm A) of the randomised arm of the trial.

Treatment:

Radiation: dose-intensified image-guided SBRT using simultaneous integrated boost