Clinical trial NCT00220675: Erythropoietin Spinal Cord Compression Randomized Trial
Official title: Recombinant Human Erythropoietin (r-HuEPO) in the Prevention of Neurologic Sequelae From Malignant Spinal Cord Compression: a Multi-Center, Placebo-Controlled, Phase 2 Randomized Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Nerve Compression Syndromes
Keywords: Malignant extradural spinal cord compression
Erythropoietin
Neuroprotectant
Radiotherapy
Palliation
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Ortho Biotech, Inc.
First posted: 2005-09-22
Enrollment: 7
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine whether erythropoietin, steroids and radiotherapy is safe and feasible to administer to patients with malignant spinal cord compression.

Detailed description: For patients with malignant spinal cord compression (MSCC) who are paraparetic or paraplegic before initiating treatment, the current treatment options provide a meager to poor chance of neurologic recovery and the prognosis is guarded. Improving the chance of ambulation after treatment for MSCC may dramatically improve patients' quality of life, decrease days spent in hospital and improve survival. Steroids appear to prevent neurologic damage from MSCC and increasing doses appear to have an increasingly protective effect, however, higher doses are limited by an increasing incidence of serious toxicity.

Recombinant human erythropoetin has been shown to improve quality of life in patients with anemia of chronic disease and animal models suggest that r-HuEPO may have a neuroprotective effect. Human studies have demonstrated increased CSF concentrations of r-HuEPO after intravenous administration, including patients with MESCC. Furthermore, there is a suggestion that patients treated with intravenous r-HuEPO, steroids and RT may recover ambulatory function to a greater degree and faster than patients not treated with r-HuEPO.

Ultimately the effect of r-HuEPO in improving neurologic, functional and quality of life outcomes will need to be tested in a properly designed, large, randomized control trial. However, in order to successfully complete this study in a timely manner, a multicenter study will need to be performed. There are logistical issues that need to be addressed when setting up a r-HuEPO infusion program.

Therefore, a multicenter, randomized phase 2 study of intravenous r-HuEPO, steroids and RT will allow the investigators to address three issues: i) confirm that the logistical issues at each center can be addressed; ii) confirm in a larger cohort of patients whether the encouraging neurologic outcomes seen in the preliminary study can be replicated across different settings when compared with a randomized control group; iii) ensure the safety of EPO in this population including overall survival and incidence of subsequent TVEs with and without EPO.

Eligibility criteria: Inclusion Criteria:

* Adults (\> 18 years old) with histopathologically confirmed cancer
* Patients unable to ambulate independently due to paraparesis or paraplegia from malignant epidural spinal cord compression (categories 2, 3, 4 in Appendix B)
* Radiotherapy offered for treatment of cord compression using 2000cGy in 5 fractions
* Informed consent signed
* Females subjects must be post-menopausal or surgically incapable of childbearing potential, must be practicing an acceptable method of birth control (i.e., hormonal contraceptives, intrauterine device or barrier and spermicide)

Exclusion Criteria:

* Uncontrolled hypertension (systolic pressure \> 160 mmHg, diastolic \> 100 mmHg) or unstable cardiovascular disease
* Previous DVT/PE or arterial embolic event
* Patients with a Hb \> 120 g/L or Hct \> 40% (for both males \& females)
* Patients with potentially curable disease
* Patients with life expectancy \< 3 months
* Patients who have received RT that would overlap with the planned treatment field
* Contraindications for MRI scan
* Women who are pregnant, or who intend to become pregnant, or who are nursing
* Patients with known brain metastases; those with a primary diagnosis of melanoma will require confirmation by CT or MRI
* Patients with a history of poorly controlled seizure disorder
* Patients with a known hypersensitivity to mammalian cell-derived products or albumin
* Patients who cannot receive adequate antithrombotic treatment, who have a hypersensitivity to the active antithrombotic substance or any of the product's excipients
* Patients who have participated in another investigational device or drug trial(s), or is receiving other investigational agent(s) within the previous 30 days
* Patients requiring neurosurgical decompression for the malignant spinal cord compression

Primary outcomes:
measure: Overall survival
measure: Recovery of ambulation
measure: Deep vein thrombosis rate post-treatment
Secondary outcomes:
measure: The time to regain ambulation
measure: Duration of ambulatory function
measure: Health-related quality of life (HRQOL, prevalence of TVE at the time of randomization
Other outcomes:
Locations:
city: London
country: Canada
facility: London Regional Health Science Center
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Center
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook & Women's College Health Science Centre
state: Ontario
Study officials:
affiliation: Sunnybrook & Women's College Health Science Centre
name: Andrew Loblaw, MD MSc
role: PRINCIPAL_INVESTIGATOR
References: