Interest of Intrathecal Chemotherapy With Liposomal Cytarabine (DepoCyte®) in Meningeal Metastasis of Breast Cancer (DEPOSEIN)

Centre Oscar Lambret

Status and phase

Completed

Phase 3

Conditions

Breast Cancer

Leptomeningeal Metastases

Treatments

Drug: Liposomal Cytarabine

Study type

Interventional

Funder types

Other

Identifiers

NCT01645839

2010-023134-23 (EudraCT Number)

DEPOSEIN-1008

Details and patient eligibility

About

The purpose of this study is to evaluate the impact of Depocyte® IT combined with the systemic standard treatment in terms of clinical and/or radiological neuromeningeal progression free survival (SSPN)

Full description

After the signature of the consent form and validation of the eligibility inclusion criteria, patients will be randomized. Treatment will start within a maximum of 10 days after randomization.

Arm A: Systemic standard treatment without DepoCyte® Arm B: Systemic standard treatment with DepoCyte® DepoCyte® will be slowly administered by injection (1 to 5 minutes) of 50 mg (5 mL) into the CSF via a lumbar puncture or a ventricular device

every 14 +/- 2 days for a total of 5 cycles (induction treatment)
then every 28 +/-4 days until progression (maintenance treatment) Standard systemic treatment by chemotherapy, targeted therapy or hormonal therapy is at the discretion of the investigator taking into account the breast cancer sub-type and previous treatments. The systemic treatment will be determined before randomization. It can be modified at any time according to the treating oncologist. Focal radiotherapy to symptomatic sites is allowed. The usual follow-up of patients treated by IT DepoCyte® of every 14 days for the first two months and then monthly is not modified in patients of Arm B. Evaluation in Arm A will be matched to Arm B, and are thus more frequent than routinely done because such patients are usually seen every 3 weeks. The follow-up for systemic disease is left at the discretion of the treating oncologist.

Translational research Only Oscar Lambret Center will participate in this exploratory analysis. For patients who accept to participate, a 10 mL CSF sample will be collected at enrollment and once per month, just before treatment.

Arm A: at monthly visit
Arm B: at a IT injection, once per month, just before DepoCyte® injection Samples will be sent to the analysis center as soon as possible and will be destroyed at the end of all study-related procedures.

Enrollment

74 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically proven invasive breast cancer
New diagnosis of leptomeningeal metastasis confirmed by CSF cytology, or by the combination of typical clinical symptoms or signs with typical MRI abnormalities
Cerebrospinal MRI criteria: no visible lesion, or meningeal metastases <0.5 cm, or >0.5 cm largest diameter if focal radiotherapy planned
Indication for systemic treatment (chemotherapy and/or targeted therapy and/or hormonal therapy) at the time of enrollment. Systemic treatment is at the discretion of the investigator (in collaboration with the treating oncologist if different) according to cancer characteristics, previous treatments, and clinical and biological disease characteristics. Focal radiotherapy is permitted.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Patients unable to walk due to a palsy but able to use a wheelchair are considered as ambulatory patients
Expected survival of at least 2 months. Patients with rapidly progressive systemic disease are not eligible for this trial
Co-existing asymptomatic brain metastases are permitted
In case of suspicion of CSF flow block, or after focal radiotherapy for the treatment of a CSF flow block, a CSF flow study will be performed (isotopic method) to confirm the absence of CSF block
Patients must have recovered from acute adverse events of other anticancer treatments previously administered
Adequate bone marrow, renal, and hepatic function with the following range: bilirubin ≤ 3 x upper limit of normal (ULN), ASAT ≤ 2.5 x ULN or ≤ 5 x ULN in presence of liver metastases
Adequate contraception (CPMP/ICH/286/95) for patients of reproductive potential (e.g., barrier method, vasectomy of partner, abstinence) (hormonal contraception not permitted)
Patient affiliated to the French Social Security
Able to understand the requirements of the study, date and sign written informed consent

Exclusion criteria

Leptomeningeal metastasis related to other primary tumors than breast cancer
History of other cancer (<5 years) except adequately treated cervical cancer, or basocellular or spinocellular skin cancer
Contra-indication to MRI (including claustrophobia)
MRI criteria: CSF flow obstruction (hydrocephalus on brain MRI or obstacle on spinal MRI)
Contra-indication to lumbar puncture and to implantation of a ventricular device
Progressive brain metastases thought to require whole brain radiotherapy
Prior cranio-spinal irradiation (prior brain focal radiotherapy or whole brain radiotherapy for brain metastases permitted)
Prior intrathecal chemotherapy or targeted therapy
Prior systemic cytarabine treatment or prior systemic high-dose methotrexate treatment
Concomitant systemic high-dose methotrexate treatment
Ventriculo-peritoneal shunt
Active infection (systemic or CNS)
Hypersensitivity to cytarabine or DepoCyte
Patient presenting with other severe non-controlled disease which could compromise the participation in the study (infection, cardio-vascular disease, gastro-intestinal disease, renal disease, pulmonary disease)
Enrollment into another study evaluating a drug within 30 days before the screening visit
Breast feeding woman or pregnancy. Nursing is not permitted for 6 months after the study
Impossibility to adhere to the requirements of the study for geographic, social or psychological reasons