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

Primary Purpose

Spinal Metastasis

Status

Active

Phase

Phase 2

Locations

Switzerland

Study Type

Interventional

Intervention

dose-intensified image-guided SBRT using simultaneous integrated boost

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

About this trial

This is an interventional treatment trial for Spinal Metastasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

UniversitätsSpital Zürich, Klinik für Radio-Onkologie

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

SBRT (Arm A)

Conventional Radiation Therapy (Arm B)

SBRT (prospective observational)

Arm 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.

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.

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

Outcomes

Primary Outcome Measures

Pain response - improvement by ≥ 2 points on the pain Visual Analogue Scale at 6 months post-treatment at the treatment site

Secondary Outcome Measures

Local metastasis control

Local metastasis control is defined from the day of randomization to a day of local (at the site of the treated spinal metastasis) progression, i.e. local failure, determined on control MR images as a change in signal intensity or on CT images as increasing soft-tissue mass. Increased epidural disease or enlargement of paraspinal disease on control images will be documented as progression.

Overall survival

Overall survival is defined from the day of randomization to a day of death of any cause.

Cancer-specific survival

Cancer-specific survival is defined from the day of randomization to a day of death due to cancer progression.

Quality-of-life (QoL)

Quality-of-life (QoL) as measured by the EORTC QLQ-C15-PL, EORTC-BM22 and EQ-5D-5L patient reported questionnaires

Epidural spinal cord compression

Epidural spinal cord compression (ESCC) will be scored using Bilsky criteria.

Acute and late toxicity

Acute aund late toxicity will be assessed in accordance to NCI CTCEA version 4.03 criteria.

Full Information

NCT ID

NCT02800551

First Posted

April 29, 2016

Last Updated

May 15, 2023

Sponsor

University of Zurich

1. Study Identification

Unique Protocol Identification Number

NCT02800551

Brief Title

Clinical Trial Comparing Dose-intensified SBRT With Conventional Radiation Therapy for Spinal Metastases

Acronym

DOSIS RCT

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

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

July 8, 2016 (Actual)

Primary Completion Date

January 13, 2023 (Actual)

Study Completion Date

July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Zurich

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Spinal Metastasis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

219 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SBRT (Arm A)

Arm Type

Experimental

Arm Description

Arm Title

Conventional Radiation Therapy (Arm B)

Arm Type

Active Comparator

Arm 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.

Arm Title

SBRT (prospective observational)

Arm Type

Experimental

Arm 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.

Intervention Type

Radiation

Intervention Name(s)

dose-intensified image-guided SBRT using simultaneous integrated boost

Intervention Type

Radiation

Intervention Name(s)

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

Primary Outcome Measure Information:

Title

Pain response - improvement by ≥ 2 points on the pain Visual Analogue Scale at 6 months post-treatment at the treatment site

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Local metastasis control

Description

Time Frame

up to 2 years

Title

Overall survival

Description

Overall survival is defined from the day of randomization to a day of death of any cause.

Time Frame

up to 2 years

Title

Cancer-specific survival

Description

Cancer-specific survival is defined from the day of randomization to a day of death due to cancer progression.

Time Frame

up to 2 years

Title

Quality-of-life (QoL)

Description

Quality-of-life (QoL) as measured by the EORTC QLQ-C15-PL, EORTC-BM22 and EQ-5D-5L patient reported questionnaires

Time Frame

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

Title

Epidural spinal cord compression

Description

Epidural spinal cord compression (ESCC) will be scored using Bilsky criteria.

Time Frame

up to 2 years

Title

Acute and late toxicity

Description

Acute aund late toxicity will be assessed in accordance to NCI CTCEA version 4.03 criteria.

Time Frame

Acute toxicity: up to 3 months; late toxicity: from 3 months up to 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Matthias Guckenberger, Prof. Dr.

Organizational Affiliation

Universitätsspital Zürich

Official's Role

Principal Investigator

Facility Information:

Facility Name

UniversitätsSpital Zürich, Klinik für Radio-Onkologie

City

Zürich

ZIP/Postal Code

8091

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Clinical Trial Comparing Dose-intensified SBRT With Conventional Radiation Therapy for Spinal Metastases

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