Clinical trial NCT00854867: Study to Demonstrate the Safety of WBR Administered at the Same Time as Intrathecal Liposomal Cytarabine (DepoCyte®) Versus Intrathecal Liposomal Cytarabine (DepoCyte®) Administered After WBR for the Treatment of Solid Tumour Neoplastic Meningitis in Patients With or Without Brain Metastasis.
Official title: Phase I Randomised Multi-centre Study to Demonstrate the Safety of WBRT Concomitant to Intrathecal Liposomal Cytarabine (DepoCyte®) Versus WBRT & Sequential Intrathecal Liposomal Cytarabine (DepoCyte®) for Treatment of STNM With or Without Brain Metastasis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumour Neoplastic Meningitis
Brain Metastases
Keywords: Solid tumour neoplastic meningitis
STNM
leptomeningeal metastases
DepoCyte
WBRT
Whole Brain Radiotherapy
Liposomal cytarabine intrathecal
Solid Tumour Neoplastic Meningitis with or without brain metastasis
Lead sponsor: Mundipharma Research Limited
Sponsor class: INDUSTRY
First posted: 2009-03-03
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to demonstrate the safety of giving Whole Brain Radiotherapy (WBRT) together with intrathecal liposomal cytarabine (DepoCyte®) for patients with leptomeningeal metastases. The study will compare the safety of giving DepoCyte at the same time as WBRT with giving the drug after WBRT is complete.


Eligibility criteria: Indication and Criteria for Inclusion/Exclusion:

Subjects who are to be included in the study have to meet all of the following criteria:

* Informed consent
* Male and female, age over 18 years
* Solid tumour neoplastic meningitis as demonstrated by a positive lumbar CSF cytology (obtained within 21 days prior to treatment initiation) OR Characteristic signs and symptoms of neoplastic meningitis PLUS an MRI indicating the presence of meningeal tumour (diagnosis to be made by neuro-oncologist and confirmed / signed within the CRF). All MRIs will be forwarded for central review and confirmation of diagnosis. In case of discrepancy the central review overrides the assessment of the investigator.
* CSF flow abnormality excluded by either an MRI scan or a 99Tc-DTPA or 111In-DTPA flow study.

(If a flow abnormality is initially demonstrated but the flow block is subsequently documented by another flow study or MRI scan to be relieved following limited field radiation therapy, the subject may then be eligible)

* If brain metastasis confirmed (including subjects who have had previous stereotactical radiosurgery or solitary lesion brain surgery) the lesion should be less than 3cm diameter
* Mini Mental State Examination (MMSE) score more than 24
* ECOG performance status 0-2

Laboratory values as follows:

* Platelet count more than or equal to 80,000/mm3
* ANC more than or equal to 1,000/mm3
* Serum creatinine less than or equal to 2 x upper limit of normal
* Total bilirubin less than or equal to 3 x upper limit of normal
* SGOT (AST) less than or equal to 3 x upper limit of normal
* LDH less than or equal to 3 x upper limit of normal

  * Females of child-bearing potential must have a negative (urine or serum) pregnancy test within 21 days prior to the start of study treatment.
  * Females of childbearing potential must be willing to use an effective method of contraception to prevent pregnancy for the duration of the study (e.g. implants, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence or vasectomised partner).
  * Males must be willing to use an effective method of contraception with their partner to prevent pregnancy for the duration of the study (e.g. implants, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence or vasectomy).

Exclusion Criteria:

* Previous WBRT
* Brain metastases more than 3 cm diameter
* Previous IT treatment
* Uncontrolled infection including HIV infection
* Any present condition that is regarded as contraindication for WBRT and intrathecal chemotherapy
* Prior treatment with systemic ARA-C
* Anticipated hypersensitivity to DepoCyte or ARA-C
* Clinically manifest encephalopathy
* On anticoagulant therapy
* Ventricular peritoneal CSF drain in situ
* Subjects unable to comply with study procedures
* Pregnancy and lactation Any other investigational drug administered within 21 days prior to study entry

Primary outcomes:
measure: To demonstrate that WBRT concomitant to DepoCyte is as safe as WBRT & sequential DepoCyte in treating solid tumour neoplastic meningitis with/without brain metastasis.
timeFrame: Safety is reviewed at every visit & for 3 months after last Depocyte administration
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Safety is reviewed at every visit & for 3 months after last Depocyte administration
measure: Progression free survival (PFS)
timeFrame: Safety is reviewed at every visit & for 3 months after last Depocyte administration
measure: Time to neurologial progression (TNP)
timeFrame: Safety is reviewed at every visit & for 3 months after last Depocyte administration
measure: Overall survival (OS)
timeFrame: Safety is reviewed at every visit & for 3 months after last Depocyte administration
Other outcomes:
Locations:
city: Feldkirch
country: Austria
facility: Feldkirch Regional Hospital
city: Graz
country: Austria
facility: Graz Medical University
city: Innsbruck
country: Austria
facility: Univeristy Clinic for Radiotherapy and Radio-Oncology
city: Klagenfurt
country: Austria
facility: Klagenfurt Regional Hospital
city: Salzburg
country: Austria
facility: University Internal Medicine Clinic III
city: Vienna
country: Austria
facility: Kaiser-Franz-Josef-Spital
city: Heidelbert
country: Germany
Study officials:
References: