Efficacy of a Radio-Biological Based Re-Irradiation Strategy for Patients With Malignant Spinal Cord Compression

Condition(s) targeted: Malignant Spinal Cord Compression

Intervention: Radiotherapy: Radio-Biological Based Re-irradiation (Radiation); Radiotherapy: Radio-Biological Based Re-irradiation (Radiation)

Phase: Phase 2

Status: Recruiting

Sponsored by: St. Luke's Hospital, Ireland

Official(s) and/or principal investigator(s):
Pierre Thirion, MD, Principal Investigator, Affiliation: St. Luke's Hospital, Ireland
Michael Moriarty, MD, Principal Investigator, Affiliation: St. Luke's Hospital, Ireland

Overall contact:
Angela Clayton-Lea, BSc (Hons), Phone: 00353 -1-4065000, Ext: 5466, Email: angela.claytonlea@slh.ie

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.

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

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

Primary outcome: 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.

Secondary outcome:

Quality of life - assessed by the EORTC QLQ-C15 PAL version 1.0

Non-spinal radiation-induced toxicity - assessed using standard RTOG criteria

Rate of long-term spinal toxicity - assessed using RTOG SOMA morbidity grading system.

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Angela Clayton-Lea, BSc (Hons), Phone: 00353 -1-4065000, Ext: 5466, Email: angela.claytonlea@slh.ie

St. Luke's Hospital, Highfield Road, Rathgar, Dublin 6,, Ireland; Recruiting
Pierre Thirion, MD, Principal Investigator
Michael Moriarty, MD, Principal Investigator
Cormac Small, MB, BCh, BAO, Sub-Investigator
Orla McArdle, MB FFRRCSI, Sub-Investigator
Dr Conor Collins, FRCPI FRCR, Sub-Investigator
Angela Clayton-Lea, BSc (Hons), Sub-Investigator

Related publications:

Marcus RB Jr, Million RR. The incidence of myelitis after irradiation of the cervical spinal cord. Int J Radiat Oncol Biol Phys. 1990 Jul;19(1):3-8.

Fowler JF. Short and long fractionated schedules in radiotherapy and a proposed improvement. Br J Radiol. 1987 Aug;60(716):777-9. No abstract available.

Ang KK, Jiang GL, Feng Y, Stephens LC, Tucker SL, Price RE. Extent and kinetics of recovery of occult spinal cord injury. Int J Radiat Oncol Biol Phys. 2001 Jul 15;50(4):1013-20.

Nieder C, Milas L, Ang KK. Tissue tolerance to reirradiation. Semin Radiat Oncol. 2000 Jul;10(3):200-9. Review.

Nieder C, Grosu AL, Andratschke NH, Molls M. Update of human spinal cord reirradiation tolerance based on additional data from 38 patients. Int J Radiat Oncol Biol Phys. 2006 Dec 1;66(5):1446-9. Epub 2006 Nov 2. Review.

Starting date: January 2008
Ending date: December 2009
Last updated: May 14, 2008