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

NCT ID: NCT01645839

Last Updated: 2019-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-30
• Study Completion Date: 2019-03-01

Brief Summary

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)

Detailed 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.

Conditions

Breast Cancer; Leptomeningeal Metastases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Systemic treatment with Depocyte

Intrathecal injection of Liposomal Cytarabine (Depocyte®) every 14 ± 2 days for a total of 5 cycles and then every 28 ± 4 days until progression.

Group Type: EXPERIMENTAL

Liposomal Cytarabine

Intervention Type: DRUG

50mg (5 mL) by slow intrathecal injection (1-5 minutes) directly into the cerebrospinal fluid (CSF) via a ventricular catheter directly into the lumbar sac during a lumbar puncture.

Systemic treatment without Depocyte

No intrathecal injection.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Liposomal Cytarabine

50mg (5 mL) by slow intrathecal injection (1-5 minutes) directly into the cerebrospinal fluid (CSF) via a ventricular catheter directly into the lumbar sac during a lumbar puncture.

Intervention Type: DRUG

Other Intervention Names

Depocyte; Aracytine

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Centre Oscar Lambret

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emilie LERHUN, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Oscar Lambret

Locations

Centre Hospitalier Universitaire Groupe Sud

Amiens, , France

Centre Hospitalier Universitaire Lyon

Bron, , France

Centre G.F. Leclerc

Dijon, , France

CHU de Grenoble

Grenoble, , France

Centre Oscar Lambret

Lille, , France

Centre Hospitalier Bretagne Sud

Lorient, , France

Centre Val d'Aurelle

Montpellier, , France

Centre Hospitalier Universitaire de Nice

Nice, , France

Centre Antoine Lacassagne

Nice, , France

Hôpital Salpétrière

Paris, , France

Countries

France

References

Le Rhun E, Wallet J, Mailliez A, Le Deley MC, Rodrigues I, Boulanger T, Lorgis V, Barriere J, Robin YM, Weller M, Bonneterre J. Intrathecal liposomal cytarabine plus systemic therapy versus systemic chemotherapy alone for newly diagnosed leptomeningeal metastasis from breast cancer. Neuro Oncol. 2020 Apr 15;22(4):524-538. doi: 10.1093/neuonc/noz201.

Reference Type: DERIVED

PMID: 31637444 (View on PubMed)

Other Identifiers

2010-023134-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DEPOSEIN-1008

Identifier Type: -

Identifier Source: org_study_id