Intrathecal chemotherapy with liposomal ara-C (Depocyte) in leptomeningeal metastases of solid tumors: a phase III study

• Register: EUCTR
• Last refreshed on: 26 June 2012
• Main ID: EUCTR2007-000179-41-GB
• Date of registration: 17/06/2008
• Prospective Registration: Yes
• Primary sponsor: Mundipharma Research Ltd
• Public title: Intrathecal chemotherapy with liposomal ara-C (Depocyte) in leptomeningeal metastases of solid tumors: a phase III study
• Scientific title: Intrathecal chemotherapy with liposomal ara-C (Depocyte) in leptomeningeal metastases of solid tumors: a phase III study
• Date of first enrolment: 10/07/2008
• Target sample size: 152
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-000179-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: standard arm

Countries of recruitment

Belgium, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
•Patients with histological proof of lung or breast cancers.
•Newly diagnosed leptomeningeal metastases confirmed by positive lumbar cerebrospinal fluid (CSF) cytology obtained within 21 days prior to registration (in case of characteristic signs and symptoms plus a suspected MRI or CT finding, two negative CSF cytology should be obtained to exclude these patients).
•Patients must be fit for IT treatment via the lumbar route.
•= 18 years and = 70 years
•KPS 70-100.
•Adequate hematological, renal, hepatic function

Platelet count = 75 x 10exp9/L
ANC = 1 x 10 exp9/L
Serum creatinine = 1.5 x upper limit of normal (ULN)
Total bilirubin = 3 x ULN
SGOT (AST) = 2.5 x ULN
= 5 x ULN in case of hepatic metastasis
LDH = 2.5 x ULN
= 5 x ULN in case of hepatic metastasis
•All patients (male and female) must use effective contraception methods according to CPMP/ICH/286/95 if of reproductive potential (e.g. implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner).
•Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.

All registered patients should undergo a CSF flow study, but only patients without significant CSF blocks are eligible for randomization.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Leptomeningeal metastases from hematological malignancies.
•Patients with leptomeningeal metastases from primary CNS tumors.
•Patients with a clinically manifest encephalopathy interfering with every day activities like dressing.
•No clinically symptomatic brain metastases (unless related to the leptomeningeal metastases: lesions (with a width of <2 cm) in continuity with the subarachnoid space are eligible.)
•Patients with rapidly progressive systemic disease or extensive systemic disease with limited survival expectancy i.e. patients with a life expectancy of less than 3 months.
•blood clotting disorders, interfering with lumbar punctures. Patients should not be under any anticoagulant treatment including low molecular weight heparins, but low dose prophylactic treatment with low molecular weight heparins is allowed.
•prior treatment with systemic ARA-C.
•Patients should not have received prior neuraxis radiotherapy.
•prior IT treatment.
•ventricular peritoneal (or similar) CSF drain.
•active systemic or CSF infection.
•known hypersensitivity to ARA-C or DepoCyte®.
•Other concurrent investigational agent during the study (leptomeningeal CNS disease would be anyway an exclusion criteria for most trials on investigational agents).
•Subjects who have received an investigational medicinal product within 30 days of study entry (defined as the baseline visit)
•Females must not be pregnant (pregnancy test) or lactating.

Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Leptomeningeal metastasis (LM) from solid tumors, in adult patients .
MedDRA version: 9.1 Level: LLT Classification code 10024233 Term: Leptomeningeal metastases

Intervention(s)

Trade Name: DEPOCYTE
Pharmaceutical Form: Suspension for injection

Primary Outcome(s)

Primary end point(s): The primary endpoint for the assessment of the clinical benefit will be Neurological progression free survival.

Main Objective: The main objective is to assess the clinical benefits of treatment with DepoCyte® in comparison to no Intra Thecal (IT) therapy in adult patients with leptomeningeal metastasis (LM) from solid tumors.

Secondary Objective: The current study allows the collection of CSF samples at baseline from all patients, which allows investigating prognostic significance of proteins. Moreover, in the DepoCyte® treated arm follow-up samples will be available, allowing the assessment of markers that correlate with disease activity and response. The correlation of proteins with survival, CSF leukocyte counts, total protein and cytology within the realms of a prospective trial will allow meaningful conclusions on the value of these proteins. This will be done by assessing some of the already identified overexpressed proteins in LM (VEGF, IL-8), but also by proteomics of CSF samples obtained within this study.

Secondary ID(s)

26051

2007-000179-41-BE