Official Title: “A Phase II Trial Evaluating the Efficacy of a Radio-Biological Based Re-Irradiation Strategy for Patients With Malignant Spinal Cord Compression”

This Phase II trial will assess and evaluate the efficacy of re-irradiation in patients presenting with malignant spinal cord compression occurring in a previously irradiation area of spinal cord.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2009

The occurrence of Malignant Spinal Cord Compression (MSCC) in a previously irradiated area of spinal cord is a common clinical situation in oncology. Only a minority of patients are amenable to non-radiotherapy management i.e, decompression spinal surgery. Therefore, re-irradiation is often considered as the unique therapeutic option for these patients.

The re-irradiation schedule for eligible patients will be in line with in-house guidelines on cumulative Biologically Effective Dose (BED) ie., ≤100 Gy2 (<6 months since most recent RT) or ≤130 Gy2 (>6 months since most recent RT). Adherence to these guidelines ensures that the cumulative dose delivered to eligible patients carries a low or intermediate risk only, for development of radiation-induced myelopathy (RIM). The re-irradiation schedule delivered will ensure that the patient receives at least the lowest dose equivalent known to have demonstrated efficacy in MSCC, and will deliver 3Gy per fraction. The re-irradiation schedule will be determined according to two parameters : - - The interval since the last course of radiotherapy to the involved area of spinal cord - The dose received to date - using BED conversion

All patients with progressive or new neurological symptoms will have an MRI of the spine performed, which is the gold standard for imaging spinal cord. Tumour progression or recurrence is a major deferential diagnosis. All MRI's will be reviewed by a consultant radiologist. All cases with RTOG SOMA score 2+ will be handled as a serious adverse event. A review of the incidence of RTOG SOMA grade 2+ will be conducted following 14 evaluable patients: if the overall rate of RIM observed exceeds the rate reported by Nieder et al (i.e., 3% for low risk patients, 25% for intermediate risk patients) by one patient - the trial will stop.

All patients will be prescribed high-dose corticosteroids (Dexamethasone), commencing with 8mg tds and tapered according to patient response. A proton-pump inhibitor may also be prescribed, in line with current practice. All patients receiving treatment to fields below the level of T9 will receive ondansetron (Zofran) 8mg p.o. prophylactically as an anti-emetic, as per current practice.

Intervention(s) in this Clinical Trial

• Radiation: Radiotherapy: Radio-Biological Based Re-irradiation
  • Fractionation scheme using 3 Gy per fraction resulting in a cumulative BED of 100Gy2 (less than six months since most recent RT)
• Radiation: Radiotherapy: Radio-Biological Based Re-irradiation
  • Fractionation scheme using 3 Gy per fraction resulting in a cumulative BED of 130Gy2 (more than six months since most recent RT)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Patients who received their most recent course of radiotherapy to the same area of spinal cord within the last six months
• Experimental: 2
  • Patients who received their most recent course of radiotherapy to the same area of spinal cord more than six months ago

Primary Measures

• Efficacy - evaluated by the response rate, based on mobility score using the Tomita scale. An improvement in mobility or stable mobility score will be regarded as a response.
  • Time Frame: Pre-reirradiation status, 1 week, 5 weeks, 3 months and every 3 months until death
    Safety Issue?: No

Secondary Measures

• Quality of life - assessed by the EORTC QLQ-C15 PAL version 1.0
  • Time Frame: Pre-reirradiation status, 1 week, 5 weeks, 3 months and every 3 months until death
    Safety Issue?: No
• Non-spinal radiation-induced toxicity - assessed using standard RTOG criteria
  • Time Frame: 1 week, 5 weeks, 3 months and every 3 months until death
    Safety Issue?: Yes
• Rate of long-term spinal toxicity - assessed using RTOG SOMA morbidity grading system.
  • Time Frame: From clinical detection (usually 9 - 15 months post irradiation)
    Safety Issue?: Yes

Inclusion Criteria:

• Histologically proven malignancy other than primary tumours of the spine or vertebral column
• Diagnosis of malignant spinal cord compression confirmed on MRI
• MRI of the entire spine performed
• Previous treatment with radiotherapy to the involved area of spinal cord, e.g., full segment and/or at least 2cm in cranio-caudal of overlap between the two areas treated
• The maximum BED received from previous irradiation should be less than or equal to 90Gy2
• Age >18 yrs
• Written informed consent obtained

Exclusion Criteria:

• Previous treatment with radiotherapy to the involved area of the spinal cord such that further treatment exceeds the relevant cumulative BED limit, in accordance with in-house guidelines on re-irradiation fo spinal cord
• Patients deemed suitable for neurosurgical intervention at the time of initial assessment (patients deemed inoperable are eligible)
• Patients, who have a medical or psychiatric condition, which in the opinion of the investigator/research team, contraindicate the patient's participation in this trial

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: St. Luke's Hospital, Ireland

Overall Clinical Trial Officials and Contacts

Pierre Thirion, MD Principal Investigator St. Luke's Hospital, Ireland  

Overall Contact: Angela Clayton-Lea, BSc (Hons) 00353 -1-4065000 angela.claytonlea@slh.ie

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00624507

Study ID Number: ICORG 07-11

ClinicalTrials.gov Identifier: NCT00624507

Health Authority: Ireland: Medical Ethics Research Committee