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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Centre Oscar Lambret
Sponsor:
Information provided by (Responsible Party):
Centre Oscar Lambret
ClinicalTrials.gov Identifier:
NCT01645839
First received: July 16, 2012
Last updated: July 28, 2016
Last verified: July 2016
  Purpose
The purpose of this study is to compare the neurological progression free survival with the use of an intrathecal chemotherapy with liposomal cytarabine (DepoCyte®) in leptomeningeal metastasis of breast cancer (versus no intrathecal treatment).

Condition Intervention Phase
Breast Cancer
Drug: Liposomal Cytarabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Interest of Intrathecal Chemotherapy With Liposomal Cytarabine (DepoCyte®) in Meningeal Metastasis of Breast Cancer. Randomized Phase III Study.

Resource links provided by NLM:


Further study details as provided by Centre Oscar Lambret:

Primary Outcome Measures:
  • Neurological Progression Free Survival [ Time Frame: At baseline ]
    Time between the date of randomization and the date of first neurological progression (or the date of death if it comes first).

  • Neurological Progression Free Survival [ Time Frame: Every 2 weeks for 2 months ]
    Time between the date of randomization and the date of first neurological progression (or the date of death if it comes first).

  • Neurological Progression Free Survival [ Time Frame: After 2 months from baseline once a month until progression (up to 6 months) ]
    Time between the date of randomization and the date of first neurological progression (or the date of death if it comes first).

  • Neurological Progression Free Survival [ Time Frame: At the end of the study (up to 6 months) ]
    Time between the date of randomization and the date of first neurological progression (or the date of death if it comes first).


Secondary Outcome Measures:
  • Frequency and timepoint of neurological, physical, cognitive, cytological and radiological improvement. [ Time Frame: At baseline ]
  • Frequency and timepoint of neurological, physical, cognitive, cytological and radiological improvement. [ Time Frame: Every two weeks for 2 months ]
  • Frequency and timepoint of neurological, physical, cognitive, cytological and radiological improvement. [ Time Frame: After 2 months from baseline once a month until progression (up to 6 months) ]
  • Frequency and timepoint of neurological, physical, cognitive, cytological and radiological improvement. [ Time Frame: At the end of the study (up to 6 months) ]
  • Clinical progression free survival [ Time Frame: At baseline ]
  • Clinical progression free survival [ Time Frame: Every 2 weeks for 2 months ]
  • Clinical progression free survival [ Time Frame: After 2 months from baseline once a month until progression (up to 6 months) ]
  • Clinical progression free survival [ Time Frame: At the end of the study (up to 6 months) ]
  • Cytological progression free survival [ Time Frame: At baseline ]
  • Cytological progression free survival [ Time Frame: Every 2 weeks for 2 months ]
  • Cytological progression free survival [ Time Frame: After 2 months from baseline once a month until progression (up to 6 months) ]
  • Cytological progression free survival [ Time Frame: At the end of the study (up to 6 months) ]
  • Radiological progression free survival [ Time Frame: At baseline ]
  • Radiological progression free survival [ Time Frame: Every 2 months ]
  • Radiological progression free survival [ Time Frame: At the end of the study (up to 6 months) ]
  • Overall survival [ Time Frame: 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 [ Time Frame: Up to 30 days after the last administration of the study treatment ]

Other Outcome Measures:
  • Research and quantification of tumor cells in the CSF by the Veridex technique for the diagnosis and monitoring of meningeal metastasis of breast cancer. [ Time Frame: At baseline ]
  • Research and quantification of tumor cells in the CSF by the Veridex technique for the diagnosis and monitoring of meningeal metastasis of breast cancer. [ Time Frame: Every 2 weeks for 2 months ]
  • Research and quantification of tumor cells in the CSF by the Veridex technique for the diagnosis and monitoring of meningeal metastasis of breast cancer. [ Time Frame: After 2 months from baseline once a month until progression (up to 6 months) ]
  • Research and quantification of tumor cells in the CSF by the Veridex technique for the diagnosis and monitoring of meningeal metastasis of breast cancer. [ Time Frame: At the end of the study (up to 6 months) ]
  • Quality of life (questionnaire QLQ C30, BN20 and C15) [ Time Frame: At baseline ]
  • Quality of life (questionnaire QLQ C30, BN20 and C15) [ Time Frame: Every 2 weeks for 2 months ]
  • Quality of life (questionnaire QLQ C30, BN20 and C15) [ Time Frame: After 2 months from baseline once a month until progression (up to 6 months) ]
  • Quality of life (questionnaire QLQ C30, BN20 and C15) [ Time Frame: At the end of the study (up to 6 months) ]
  • Autonomy in daily life (questionnaire Instrumental Activities in Daily Living) [ Time Frame: At baseline ]
  • Autonomy in daily life (questionnaire Instrumental Activities in Daily Living) [ Time Frame: Every 2 weeks for 2 months ]
  • Autonomy in daily life (questionnaire Instrumental Activities in Daily Living) [ Time Frame: After 2 months from baseline once a month until progression (up to 6 months) ]
  • Autonomy in daily life (questionnaire Instrumental Activities in Daily Living) [ Time Frame: At the end of the study (up to 6 months) ]
  • Emotional state of the patient assessed by the psychological distress score [ Time Frame: At baseline ]
  • Emotional state of the patient assessed by the psychological distress score and the Patients' Global Impression of Change (PGIC) scale. [ Time Frame: Every 2 weeks for 2 months ]
  • Emotional state of the patient assessed by the psychological distress score and the Patients' Global Impression of Change (PGIC) scale. [ Time Frame: After 2 months from baseline once a month until progression (up to 6 months) ]
  • Emotional state of the patient assessed by the psychological distress score and the Patients' Global Impression of Change (PGIC) scale. [ Time Frame: At the end of the study (up to 6 months) ]

Estimated Enrollment: 80
Study Start Date: August 2011
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Other Names:
  • Depocyte
  • Aracytine
No Intervention: Systemic treatment without Depocyte
No intrathecal injection.

Detailed Description:

Patients eligible for the trial and having signed their consent to participate will be randomized to arm A or B.

  • Arm A: Standard systemic treatment without Depocyte®
  • Arm B: Standard systemic treatment with Depocyte®

Patients randomized to arm B will receive an intrathecal injection of Depocyte® every 14 ± 2 days for a total of 5 cycles and then every 28 days until progression. The treatment should begin in the days following the randomization (maximum 10 days).

The nature of the standard systemic treatment (chemotherapy, hormone therapy or targeted therapy) will be left to the discretion of the investigator according to the subtype of the breast cancer and according to the treatments already received. It will be determined prior to randomization. It can be amended at any time upon notice of the patient's referent oncologist. A focal radiotherapy on symptomatic sites can also be performed if necessary.

Patients will have :

  • a clinical assessment within 3 days prior to the start of the study treatment, every 2 weeks for 2 months, then once a month until progression, and at the end of the study ;
  • a paraclinical assessment within 14 days prior to the start of the study treatment, every 2 months, and at the end of the study ;
  • and a biologic assessment within 7 days prior to the start of the study treatment, once a month until progression, and at the end of the study.

They will likewise undergo a lumbar puncture prior to the start of treatment, once a month for patients in arm A, every 2 weeks for 2 months, then once a month until progression for patients in arm B and finally at the end of the study.

They will also address questionnaires within 3 days prior to the start of the study treatment, every 2 weeks for 2 months, then once a month until progression and at the end of the study.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed invasive breast cancer.
  • New diagnosis of leptomeningeal involvement confirmed by CSF cytology or clinical signs and symptoms associated with abnormal MRI features.
  • MRI criteria : meningeal metastasis < 0.5 cm or > 0.5 cm in case of focused radiation therapy.
  • Patient requiring a systemic treatment (chemotherapy and / or targeted therapy and / or hormone therapy) at the time of inclusion. The systemic treatment is left to the discretion of the investigator in connection with the referent senologist according to the characteristics of the cancer, the previous treatments received and the clinical and biological general state. Focused radiotherapy is authorized.
  • Age ≥ 18 years
  • Performance Status (ECOG) ≤ 2. Patients unable to walk due to paralysis but moving in wheelchairs are considered to be ambulatory.
  • Life expectancy > 2 months. Patients with a rapidly progressive systemic disease are not eligible for this protocol.
  • Brain metastasis allowed if asymptomatic.
  • In case of suspicion of a CSF blocking, or after local radiotherapy for lifting a CSF blocking, a study of the flow of CSF has to be performed (isotopic method) to confirm the absence of a CSF flow blocking.
  • Patients must have recovered from the acute toxic effects of other cancer treatments received.
  • Adequate hematological, renal, hepatic parameters :

    • Total bilirubin ≤ 3 times the upper limit of normal (ULN).
    • SGOT/AST ≤ 2.5 ULN ; ≤ 5 ULN if hepatic metastasis
  • Effective contraceptive method (CPMP/ICH/286/95) for non menopausal patients (eg intrauterine device (IUD), sexual abstinence, vasectomized partner ) (no hormonal contraception).
  • Patients having a social security scheme.
  • Informed consent form signed by the patient.

Exclusion Criteria:

  • Leptomeningeal metastasis other than from breast cancer.
  • History of other cancer ( < 5 years) except cervix carcinoma, basal cell or squamous cell skin carcinoma properly treated.
  • Contraindication to MRI (including claustrophobia)
  • MRI criteria : CSF flow obstruction (hydrocephalus in brain MRI or obstacle in spinal MRI)
  • Contraindication to lumbar puncture and to ventricular catheterization.
  • Progressive brain metastasis requiring a total brain radiation therapy.
  • History of craniospinal radiotherapy (History of focal or whole brain radiation therapy for parenchymal metastasis accepted).
  • History of intrathecal treatment (lumbar or ventricular).
  • History of systemic treatment with ARA-C or high-dose systemic methotrexate.
  • Intravenous high dose concomitant treatment with methotrexate.
  • Ventriculoperitoneal shunt.
  • Active infection (systemic or cerebromeningeal).
  • Hypersensitivity to ARA-C or DepoCyte.
  • Other severe or non controlled pathology which could jeopardize the participation in the trial (infection, cardiovascular, digestive, renal, pulmonary disease).
  • Patient already included in another therapeutic trial with an experimental molecule (within 30 days before the screening visit).
  • Pregnant or breastfeeding women. Women must not breast-feed for at least 6 months.
  • Patients unable to undergo medical follow up for geographic, social or psychological reasons.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01645839

Contacts
Contact: Emilie LERHUN, MD +33 (0)320295959 e-lerhun@o-lambret.fr
Contact: Sophie TAILLIBERT, MD sophie.taillibert@psl.aphp.fr

Locations
France
Centre Hospitalier Universitaire Groupe Sud Recruiting
Amiens, France, 80054
Contact: Mathieu BOONE, MD       boone.mathieu@chru-amiens.fr   
Principal Investigator: Mathieu BOONE, MD         
Sub-Investigator: Bruno CHAUFFERT, MD         
Sub-Investigator: Christine PIPROT-CHAUFFAT, MD         
Centre Hospitalier Universitaire Lyon Not yet recruiting
Bron, France, 69677
Contact: François DUCRAY, MD       francois.ducray@chu-lyon.fr   
Principal Investigator: François DUCRAY, MD         
Sub-Investigator: Stéphanie CARTALAT-CAREL, MD         
Sub-Investigator: Laure THOMAS, MD         
Sub-Investigator: Jérôme HONORAT, MD         
Sub-Investigator: Christine TOMMASI, MD         
Centre G.F. Leclerc Recruiting
Dijon, France, 21079
Contact: Isabelle DESMOULINS, MD       idesmoulins@cgfl.fr   
Principal Investigator: Isabelle DESMOULINS, MD         
Sub-Investigator: Bruno COUDERT, MD         
Sub-Investigator: Séverine GUIU, MD         
Sub-Investigator: Pierre FUMOLEAU, MD         
Sub-Investigator: E. VIEL, MD         
Sub-Investigator: S. LADOIRE, MD         
Sub-Investigator: V. LORGIS, MD         
Sub-Investigator: A. HERVIEU, MD         
CHU de Grenoble Recruiting
Grenoble, France, 38042
Contact: Mireille MOUSSEAU, MD, PhD    04 76 76 54 51    mmousseau@chu-grenoble.fr   
Principal Investigator: Mireille MOUSSEAU, MD, PhD         
Sub-Investigator: Mathieu LARAMAS, MD         
Sub-Investigator: Cristina COSTAN, MD         
Sub-Investigator: Christine REBISCHUNG, MD         
Sub-Investigator: Oxana SHESTAEVA, MD         
Centre Hospitalier Not yet recruiting
Le Mans, France, 72000
Contact: Oana COJOCARASU, MD         
Principal Investigator: Oana COJOCARASU, MD         
Sub-Investigator: Nathalie DENIZON, MD         
Centre Oscar Lambret Recruiting
Lille, France, 59020
Contact: Emilie LERHUN, MD    +33 (0)320295959    e-lerhun@o-lambret.fr   
Principal Investigator: Emilie LERHUN, MD         
Sub-Investigator: Jacques BONNETERRE, MD, PhD         
Sub-Investigator: Laurence VANLEMMENS, MD         
Sub-Investigator: Audrey MAILLIEZ, MD         
Sub-Investigator: Véronique SERVENT, MD         
Sub-Investigator: Géraldine LAURIDANT, MD         
Centre Hospitalier Bretagne Sud Not yet recruiting
Lorient, France, 56100
Contact: Joëlle EGRETEAU, MD       j.egreteau@ch-bretagne-sud.fr   
Principal Investigator: Joëlle EGRETEAU, MD         
Sub-Investigator: Régine LAMY, MD         
Sub-Investigator: Isabelle CUMIN, MD         
Sub-Investigator: Christian SIRE, MD         
Centre Val d'Aurelle Recruiting
Montpellier, France, 34298
Contact: Michel FABBRO, MD       mfabbro@montpellier.unicancer.fr   
Principal Investigator: Michel FABBRO, MD         
Sub-Investigator: Anna DURIGOVA, MD         
Sub-Investigator: Gilles ROMIEU, MD         
Sub-Investigator: Amélie DARLIX, MD         
Sub-Investigator: S. POUDEROUX, MD         
Sub-Investigator: M. LAIGRE, MD         
Sub-Investigator: N. FIRMIN, MD         
Centre Hospitalier Universitaire de Nice Not yet recruiting
Nice, France, 06002
Contact: Christine LEBRUN FRENAY, MD       lebrun-frenay.c@chu-nice.fr   
Principal Investigator: Christine LEBRUN FRENAY, MD         
Sub-Investigator: Véronique BOURG, MD         
Centre Antoine Lacassagne Recruiting
Nice, France, 06189
Contact: Esma SAADA-BOUZID, MD         
Principal Investigator: Esma SAADA-BOUZID, MD         
Sub-Investigator: Philippe FOLLANA, MD         
Sub-Investigator: Jean-Marc FERRERO, MD         
Sub-Investigator: Marc FRENAY, MD         
Hôpital Salpétrière Recruiting
Paris, France, 75013
Contact: Augusti ALENTORN, MD    01 42 16 41 60    agusti.alentorn@aphp.fr   
Sub-Investigator: Sophie TAILLIBERT, MD         
Sub-Investigator: Caroline DEHAIS, MD         
Sub-Investigator: Caroline HOUILLIER, MD         
Sub-Investigator: Ahmed IDBAIH, MD         
Sub-Investigator: Dimitrios PSIMARAS, MD         
Sub-Investigator: Marc SANSON, MD         
Sub-Investigator: Jean-Yves DELATTRE, MD         
Sub-Investigator: Florence LAIGLE-DONADEY, MD         
Sub-Investigator: Khê HOANG-XUAN, MD         
Principal Investigator: Augusti ALENTORN, MD         
Institut Curie - Hôpital René Huguenin Not yet recruiting
Saint Cloud, France, 92210
Contact: Maya GUTIERREZ, MD       gutierrez@crh1.org   
Principal Investigator: Maya GUTIERREZ, MD         
Sub-Investigator: Fawzia MEFTI-LACHERAF, MD         
Sponsors and Collaborators
Centre Oscar Lambret
Investigators
Principal Investigator: Emilie LERHUN, MD Centre Oscar Lambret
  More Information

Responsible Party: Centre Oscar Lambret
ClinicalTrials.gov Identifier: NCT01645839     History of Changes
Other Study ID Numbers: DEPOSEIN-1008
2010-023134-23 ( EudraCT Number )
Study First Received: July 16, 2012
Last Updated: July 28, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Centre Oscar Lambret:
Leptomeningeal metastasis
Intrathecal chemotherapy
Depocyte

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasm Metastasis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 28, 2017