Intra-arterial Chemotherapy for Spinal Metastases
Condition: Spinal Diseases; Spinal Metastases; Spinal Tumors
MeSH terms: Neoplasm Metastasis; Spinal Cord Neoplasms; Spinal Neoplasms; Spinal Diseases
Study type: Interventional
Phase: Phase 1

Summary: 
      Metastatic malignant tumors comprise the vast majority of spinal tumors in adults. The most
      devastating complication of spinal metastatic disease (SMD) is invasion of the spinal canal
      and compression of the spinal cord or the nerve roots of the cauda equina, resulting in a
      clinical entity known as cord compression that manifests with progressive loss of motor
      function and sensation in the legs, as well as bladder and bowel incontinence.

      The treatment of spinal metastases is mostly palliative with the goals of improving or
      maintaining neurologic function, achieving local tumor control, and spinal stability. Most
      patients with spinal metastatic disease are currently treated effectively with radiation
      therapy and/or surgery with good results. There are however certain limitations in the
      current treatment of SMD. Radiation therapy has two important limitations: 1) if the targeted
      SMD is in close proximity the spinal cord, delivery of high radiation doses is
      contraindicated as it may cause radiation-induced damage to the spinal cord (myelopathy, and
      2) there is limit on the cumulative amount of radiation dose, which means that recurrent
      tumors may not be amenable to repeat radiation therapy. As far spinal surgery is concerned,
      the main limitation is that some patients are not fit for surgery because of medical
      co-morbidities.

      This phase I clinical research trial will test the hypothesis that a new minimally invasive
      treatment called spinal intra-arterial chemotherapy (SIAC) can be safely applied in patients
      with SMD.
    

Detailed description: 
      To date, there is no effective systemic therapy for spinal metastases, and the goal of
      treatment is to achieve local control of the tumor. Despite advances in radiation therapy,
      there is still a subgroup of patients that cannot be effectively treated with radiation
      because of close proximity of the tumor to the spinal cord. In addition, in cases of
      recurrent tumors, some patients cannot be re-treated because they reached the maximum allowed
      radiation dose. Surgery is the alternative treatment for these patients, but some tumors do
      recur after surgery while some patients have comorbidities that make surgery a high-risk
      procedure.

      Based on our prior experience with selective IA chemotherapy for the treatment of ocular
      retinoblastoma and the high local control rates achieved with selective IA injection of
      chemotherapy in recurrent limb melanoma (limb infusion and limb perfusion) we expect that
      spinal intra-arterial chemotherapy with selective injection of Melphalan in the arteries
      feeding the metastatic disease is feasible and safe and may prove beneficial in achieving
      local control of the spinal tumor, preventing neurological compromise from cord compression.
      This minimally invasive approach can be used in patients in whom radiation therapy and
      surgery are contra-indicated and essentially have no other treatment options.
    

Intervention name(s): Melphalan (intra-arterial infusion)
Intervention type(s): Drug
Intervention description(s): Patients will undergo a minimally invasive procedure called spinal angiography. This procedure will identify the arteries feeding the tumor causing cord compression and will determine whether chemotherapy can be safely infused.
The chemotherapy will be infused via a tiny soft plastic tube (called "microcatheter") at the tumor site over approximately 30 minutes.
The drug of choice is melphalan (trade name Alkeran) at a maximum dose of 16mg/m2, adjusted for white cell count, platelet count and renal function.
We will perform up to three intra-arterial chemotherapy treatments in 3-6 week intervals, based on the results of complete blood counts.
Other intervention name(s): Alkeran
Intervention MeSH terms: Melphalan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Spinal Metastases; Spinal Metastatic Disease; Cord Compression; Intra-arterial Chemotherapy; Spinal Tumors