Proton Cranio-spinal Irradiation for Leptomeningeal Metastasis

Study Overview
=================
Brief Summary
-----------------
Leptomeningeal metastasis is a rare but serious complication to cancer, with a grave prognosis. No efficient treatment exists. Recent data suggest that craniospinal radiotherapy lead to superior survival and CNS control compared to focal photon radiotherapy. We want to offer Danish patients the new treatment, but within a protocol, as this is new data with an new treatment principle

Detailed Description
-----------------
Patients with leptomeningeal metastasis from both solid and hematological cancers will be offered proton radiotherapy with 30 Gy in 10 fractions to the entire craniospinal axis. Patients will be followed with registration of side effects, neurology and MRI scans every 3 months until 1 year.

Official Title
-----------------
Phase II Study of Proton Cranio-spinal Irradiation for Leptomeningeal Metastasis

Conditions
-----------------
Leptomeningeal Metastasis

Intervention / Treatment
-----------------
* Radiation: CSI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Metastasis to the leptomeningeal space (LM) surrounding the brain and/ or spinal cord Metastasis verified by MRI or CSF cytology Karnofsky >=60 (requiring some help, can take care of most personal requirements) Adequate bone marrow function Haemoglobin > 5 mmol/l Absolute neutrophil count >1 10^9/l Platelet count > 100 10^9/l Patient consent Female subjects must either be of non-reproductive potential ( ≥ 60 years old, or with no menses for >1 year without an alternative medical cause], OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a pregnancy test within 2 weeks prior to starting treatment. Patient at reproductive potential must agree to practice an effective contraceptive method. Exclusion Criteria: • Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances (Yang) Patient with multiple, serious major neurologic deficits per physician/investigator assessment including encephalopathy Patient with extensive systemic disease and without reasonable systemic treatment options Patient who is unable to undergo MRI brain and spine with gadolinium contrast Pregnant or lactating women.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Craniospinal proton radiotherapy<br>30 Gy in 10 fractions to CNS | Radiation: CSI<br>* 30 Gy in 10 fractions to CNS<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CNS control | local control | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | actuarial | 1 year | 
| CNS-PFS dependent on tumor site | progression free survival, actuarial | 1 year | 
| Symptomatology | New symptoms, CTC AE 5.0 grade >=3 | 1 year |