Neoplasms

Symptoms and General Pathology

All Conditions

Musculoskeletal Diseases

Blood and Lymph Conditions

Neoplasm Metastasis

Neoplasms, Second Primary

Bone Neoplasms

Bone Marrow Diseases

Neoplastic Processes

Bone Diseases

Hematologic Diseases

MRI-based, cone beam CT-guided SBRT delivery of a single dose of 18 Gray (Gy) on the visible metastasis, and 8 Gy on the bony compartment containing the metastasis (e.g. the affected vertebra or pedicle).

Delivery of a single fraction of 8 Gy using virtual simulation

Stereotactic Body Radiotherapy

Helena M. Verkooijen, MD, PhD

The purpose of the study is to investigate effectiveness of stereotactic body radiotherapy in patients with bone metastatic disease.

Rationale: Bone metastases are a frequent distant manifestation of solid tumours, and many bone metastases are located in the spine. These patients mostly present with severe (back) pain which reduces quality of life. The primary treatment for pain management is a single-fraction low dose external beam radiation therapy (EBRT), effective in achieving pain reduction in around 60% of patients, of whom 0-23% experience complete pain response. Recently, there is growing evidence that Stereotactic Body Radiotherapy (SBRT) achieves a much higher pain response due to the higher dose administered. In retrospective and a few prospective case series, SBRT for spinal, and also non-spinal metastases has been demonstrated to be safe, and efficacious. However, no randomized controlled trials have been performed.

Objective: To study whether the pain response after three months in patients with osseous metastatic disease increases after SBRT in comparison to low dose EBRT.

Study design: Randomized controlled trial, the VERTICAL study, nested within the PRESENT cohort.

Study population: Eligible patients are MRI-compatible patients with radiographic evidence of bone metastases at the radiotherapy department. Fifty-five patients are recruited in both control and intervention arm.

Intervention: Patients will undergo MRI-based, cone beam CT-guided SBRT and will receive a single dose of 18 Gray (Gy) on the visible metastasis, and 8 Gy on the bony compartment containing the metastasis (e.g. the affected vertebra or pedicle).

Main study parameters/endpoints: The primary endpoint is pain control at three months after radiotherapy. Secondary outcomes are, among others, the occurrence of vertebral compression fracture (VCF) and radiation-induced myelopathy, local tumour control and evaluation of quality of life.

Randomized Trial Comparing Conventional Radiotherapy With Stereotactic Radiotherapy in Patients With Bone Metastases - VERTICAL Study

Randomized Controlled Trial Comparing Conventional Radiotherapy With Stereotactic Body Radiotherapy in Patients With Bone Metastases - VERTICAL Study

The primary endpoint of this study is complete or partial pain response after SBRT or EBRT after three months. Complete and partial response, but also possible pain progression or indeterminate response, will be defined according to the International Bone Metastases Consensus Endpoints for Clinical Trials.

Self reported quality of life as measured by the Brief Pain Inventory, European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ) C15-PAL, and EORTC QLQ BM22

Progression free survival is defined as time between treatment and first sign of progression of disease

Overall survival is defined as time between treatment and death from any cause

VCF is defined as new endplate fracture or collapse deformity as compared with before SBRT or EBRT

Radiation-induced myelopathy is defined as a diagnosis of exclusion and defined as neurological signs and symptoms consistent with radiation damage in the form of necrosis to the segment of the spinal cord irradiated, without MRI evidence of recurrent or progressive tumour affecting the spinal cord.

Duration of pain relief as measured by the Brief Pain Inventory

Rapidity of pain relief as measured by the Brief Pain Inventory

UMC Utrecht

Prof. dr.

Nervous System Diseases

Wounds and Injuries

Spinal Diseases

Spinal Cord Neoplasms

Spinal Cord Compression

Spinal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Spinal Cord Diseases

Central Nervous System Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Antineoplastic Agents

Anesthetics

Melphalan

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Subjects recruited to this study will receive intra-arterial injections of chemotherapy (melphalan) in the branches of the arteries feeding the metastatic spinal tumor. Subjects will receive general anesthesia or conscious sedation. A catheter will be guided using X-ray from the femoral artery at the top of the leg to the arteries of the spine. A dye will be injected through the catheter to show the arteries in greater detail. The chemotherapy is then injected into the tumor. We will inject the maximum systemic dose adjusted to white blood count and platelet count. Subjects will undergo three cycles of chemotherapy three to six weeks apart.

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.

Melphalan (intra-arterial infusion)

Athos Patsalides

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Randomized Trial Comparing Conventional Radiotherapy With Stereotactic Radiotherapy in Patients With Bone Metastases - VERTICAL Study	NCT02364115	Spinal Metastas... Bone Metastases	Stereotactic Bo...	18 Years -	UMC Utrecht
Randomized Trial Comparing Conventional Radiotherapy With Stereotactic Radiotherapy in Patients With Bone Metastases - VERTICAL Study	NCT02364115	Spinal Metastas... Bone Metastases	Stereotactic Bo...	18 Years -	UMC Utrecht
Intra-arterial Chemotherapy for Spinal Metastases	NCT01637766	Spinal Diseases Spinal Metastas... Spinal Tumors	Melphalan (intr...	18 Years - 80 Years	Weill Medical College of Cornell University

Spots Global Cancer Trial Database for spinal metastatic disease