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

NCT01645839 | Completed Phase 3 DMC

• 2 other identifiers: DEPOSEIN-10082010-023134-23
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 10

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)

Conditions

Breast Cancer; Leptomeningeal Metastases

Keywords

Leptomeningeal metastasis; Intrathecal chemotherapy; Depocyte

Outcome Measures

Primary Outcomes (1)

• Leptomeningeal disease-related neurological progression-free survival (LM-PFS)

  time between randomization and date of first leptomeningeal progression (defined according to clinical-neurological or imaging criteria) or date of death (death from any cause) whatever occurs first. Patients alive without neurological progression at the time of the last follow-up will be censored at the date of the last visit.

  At baseline, then every 2 weeks for 2 months, after 2 months from baseline once a month until progression (up to 6 months) and at the end of the study (up to 6 months)

Secondary Outcomes (5)

• Response of leptomeningeal metastases

  At baseline, then every 2 weeks for 2 months, after 2 months from baseline once a month until progression (up to 6 months) and at the end of the study (up to 6 months)

• Progression free survival (PFS)

  At baseline, then every 2 weeks for 2 months, after 2 months from baseline once a month until progression (up to 6 months) and at the end of the study (up to 6 months)

• Overall survival

  Until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.

• Tolerance to DepoCyte® according to NCI CTCAE V4.0

  Up to 30 days after the last administration of the study treatment

• Q-TWiST

  Calculated at the end of study

Other Outcomes (5)

• Quality of life (questionnaire QLQ C30, BN20 and C15)

  At baseline, then every 2 weeks for 2 months, after 2 months from baseline once a month until progression (up to 6 months) and at the end of the study (up to 6 months)

• Autonomy in daily life (questionnaire Instrumental Activities in Daily Living)

  At baseline, then every 2 weeks for 2 months, after 2 months from baseline once a month until progression (up to 6 months) and at the end of the study (up to 6 months)

• Emotional state of the patient assessed by the psychological distress score

  At baseline

Study Arms (2)

Systemic treatment with Depocyte

EXPERIMENTAL

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

Drug: Liposomal Cytarabine

Systemic treatment without Depocyte

NO INTERVENTION

No intrathecal injection.

Interventions

Liposomal Cytarabine 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.

Also known as: Depocyte, Aracytine

Systemic treatment with Depocyte

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Oscar Lambret: lead

Study Sites (10)

Centre Hospitalier Universitaire Groupe Sud

Amiens, 80054, France

Location

Centre Hospitalier Universitaire Lyon

Bron, 69677, France

Location

Centre G.F. Leclerc

Dijon, 21079, France

Location

CHU de Grenoble

Grenoble, 38042, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Hospitalier Bretagne Sud

Lorient, 56100, France

Location

Centre Val d'Aurelle

Montpellier, 34298, France

Location

Centre Hospitalier Universitaire de Nice

Nice, 06002, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hôpital Salpétrière

Paris, 75013, France

Location

Related Publications (1)

• 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.

  PMID: 31637444 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Meningeal Carcinomatosis

Interventions

Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Emilie LERHUN, MD

  Centre Oscar Lambret

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2012
• First Posted: July 20, 2012
• Study Start: August 30, 2011
• Primary Completion: August 1, 2018
• Study Completion: March 1, 2019
• Last Updated: June 12, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10)