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

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ClinicalTrials.gov Identifier: NCT01645839
Recruitment Status : Active, not recruiting
First Posted : July 20, 2012
Last Update Posted : March 23, 2018
Sponsor:
Information provided by (Responsible Party):
Centre Oscar Lambret

Brief Summary:
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 or disease Intervention/treatment Phase
Breast Cancer Drug: Liposomal Cytarabine Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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.
Actual Study Start Date : August 30, 2011
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Cytarabine

Arm Intervention/treatment
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.



Primary Outcome Measures :
  1. Neurological Progression Free Survival [ Time Frame: 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) ]
    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 :
  1. Frequency and timepoint of neurological, physical, cognitive, cytological and radiological improvement. [ Time Frame: 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) ]
    Percentage of patients presenting a clinical neurological, cytological and radiological response. Time between randomization and response.

  2. Clinical progression free survival [ Time Frame: 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) ]
    Neurological examination with a global cognitive assessment. Calculate the MOCA score and compare it to the scale. Clinical neurological improvement or stability.

  3. Cytological progression free survival [ Time Frame: 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) ]
    Time between the date of randomization and date of cytological progression (or date of death linked to tumor meningitis if it comes first).

  4. Radiological progression free survival [ Time Frame: 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) ]
    Time between the randomization and the occurence of radiological response regarding to MRIs (complete response, partial response, aggravation, or stability)

  5. 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. ]
    Time between the date of randomization in the study and the disease progression or the death, whatever the cause.

  6. Tolerance to DepoCyte® according to NCI CTCAE V4.0 [ Time Frame: Up to 30 days after the last administration of the study treatment ]
    The toxicity will be judged according to the NCI-CTCAE V4.0 scale. The tolerance is evaluated by the notification of the side effects at each cycle.


Other Outcome Measures:
  1. 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, 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) ]
    60 samples analysed at the diagnostic and monitoring of tumor meningitis moments, by VERIDEX technique : the presence of tumors cells is affirmed if there is more than 1 cell in 7.5 mL.

  2. Quality of life (questionnaire QLQ C30, BN20 and C15) [ Time Frame: 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) ]
    Estimated from the patient's point of view, with the QLQ C30, BN20 and C15 surveys.

  3. Autonomy in daily life (questionnaire Instrumental Activities in Daily Living) [ Time Frame: 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) ]
    IADL scale which evaluates the repercussions of the patients difficulties in the different activities of daily life.

  4. Emotional state of the patient assessed by the psychological distress score [ Time Frame: At baseline ]
    A scale composed of 6 items which evaluate the life quality of the patient (practical, physical, familial, psychological difficulties), and a numeric scale.

  5. 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, then 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) ]
    A scale of 7 levels (1 : very improved ; 7 : very aggravated) to quantify the improvement (from the last coming) felt by the patient himself and his entourage, the improvement of his clinical state by the doctor, and the gravity of the clinical state before treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01645839


Locations
France
Centre Hospitalier Universitaire Groupe Sud
Amiens, France, 80054
Centre Hospitalier Universitaire Lyon
Bron, France, 69677
Centre G.F. Leclerc
Dijon, France, 21079
CHU de Grenoble
Grenoble, France, 38042
Centre Oscar Lambret
Lille, France, 59020
Centre Hospitalier Bretagne Sud
Lorient, France, 56100
Centre Val d'Aurelle
Montpellier, France, 34298
Centre Hospitalier Universitaire de Nice
Nice, France, 06002
Centre Antoine Lacassagne
Nice, France, 06189
Hôpital Salpétrière
Paris, France, 75013
Sponsors and Collaborators
Centre Oscar Lambret
Investigators
Principal Investigator: Emilie LERHUN, MD Centre Oscar Lambret

Responsible Party: Centre Oscar Lambret
ClinicalTrials.gov Identifier: NCT01645839     History of Changes
Other Study ID Numbers: DEPOSEIN-1008
2010-023134-23 ( EudraCT Number )
First Posted: July 20, 2012    Key Record Dates
Last Update Posted: March 23, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
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