Breast CancerPhase 3DEPOSEINNCT01645839
Interest of Intrathecal Chemotherapy With Liposomal Cytarabine (DepoCyte®) in Meningeal Metastasis of Breast Cancer
A Phase 3 study testing Liposomal Cytarabine in people with Breast Cancer and Leptomeningeal Metastases, run by Centre Oscar Lambret at 10 sites in France.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Leptomeningeal Metastases
- What is being tested?
- Liposomal Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 10 sitesFrance
- Study dates
- 30 Aug 2011to 1 Mar 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
France10 sites
Centre Hospitalier Universitaire Groupe Sud
Amiens, 80054
Centre Hospitalier Universitaire Lyon
Bron, 69677
Centre G.F. Leclerc
Dijon, 21079
CHU de Grenoble
Grenoble, 38042
Centre Oscar Lambret
Lille, 59020
Centre Hospitalier Bretagne Sud
Lorient, 56100
Centre Val d'Aurelle
Montpellier, 34298
Centre Hospitalier Universitaire de Nice
Nice, 06002
Centre Antoine Lacassagne
Nice, 06189
Hôpital Salpétrière
Paris, 75013
About this study
Official title: Role of Intrathecal Chemotherapy With Liposomal Cytarabine (DepoCyte®) in Patients Wih Leptomeningeal Metastasis of Breast Cancer. A Randomized Phase III Study.
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)
Read the 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
- Being tested
- Liposomal Cytarabine
- Keywords
- Leptomeningeal metastasis, Intrathecal chemotherapy, Depocyte
- Medical subject headings
- Breast Neoplasms, Meningeal Carcinomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposomal CytarabineDrug
Also called Depocyte, Aracytine
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Liposomal Cytarabine |
| Systemic treatment without Depocyte | No intervention | No intrathecal injection. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Evaluated by clinical improvement, cytological improvement and MRI improvement. At 2 and 6 months, and best leptomeningeal disease response to treatment in response to treatment
Measured: 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)
PFS defined by the time between randomization and date of first progression: leptomeningeal, parenchymal, systemic (extra-CNS) or date of death (from any cause) if it occurs first. Patients alive and without progression at the time of the last follow-up will be censured at the date of the last visit. The different components of PFS will also be estimated considering the competing risk approach.
Measured: 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
Time between the date of randomization in the study and the death of the patient (from any cause).
Measured: 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
Safety and tolerability profile of DepoCyte® according to NCI-CTCAE v4.0. Adverse events will be considered as severe if the grade is more than 2. All AE will be taken into account except events unequivocally related to the underlying disease or its progression. SAE will be also reported.
Measured: Up to 30 days after the last administration of the study treatment
Q-TWiST
Q-TWiSTanalysis defined by 3 health status: time with toxicity before progression (TOX), time after progression (PROG) considering progression at any site, and time without toxicity and without progression (TWiST).
Measured: Calculated at the end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2012 (estimated)
- Study start30 Aug 2011
- Primary completionAug 2018
- Study completion1 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Oscar Lambret
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Emilie LERHUN, MD, Principal investigator, Centre Oscar Lambret
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01645839
- Sponsor's protocol ID
- DEPOSEIN-1008
- Other IDs
- 2010-023134-23
- Acronym
- DEPOSEIN
- Status last verified
- Jun 2019
- First submitted
- 16 Jul 2012
- Last updated
- 12 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 31637444
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Intrathecal Chemotherapy With Liposomal Cytarabine (DepoCyte®) in Patients Wih Leptomeningeal Metastasis of Breast Cancer. A Randomized Phase III Study.
- ClinicalTrials.gov ID
- NCT01645839
- Acronym / sponsor ID
- DEPOSEIN / DEPOSEIN-1008
- Conditions
- Breast Cancer, Leptomeningeal Metastases
- Keywords
- Leptomeningeal metastasis, Intrathecal chemotherapy, Depocyte
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Centre Oscar LambretUniversity, hospital or other
- Study start
- 30 Aug 2011 (actual)
- Primary completion
- Aug 2018 (actual)
- Study completion
- 1 Mar 2019 (actual)
- First posted
- 20 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Systemic treatment with Depocyte | Experimental | Drug: Liposomal CytarabineIntrathecal injection of Liposomal Cytarabine (Depocyte®) every 14 ± 2 days for a total of 5 cycles and then every 28 ± 4 days until progression. |
| Systemic treatment without Depocyte | No intervention | –No intrathecal injection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liposomal CytarabineAlso: Depocyte, Aracytine50mg (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. | Drug | Systemic treatment with Depocyte |
Primary outcome
Leptomeningeal disease-related neurological progression-free survival (LM-PFS)
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 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.
5 secondary outcomes
Response of leptomeningeal metastases
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)
Progression free survival (PFS)
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)
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
Q-TWiST
Time frame: Calculated at the end of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2019.
- Derived from this study: PubMed 31637444Le 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emilie LERHUN, MD principal investigator
Centre Oscar Lambret
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Liposomal Cytarabine in people with Breast Cancer and Leptomeningeal Metastases, run by Centre Oscar Lambret at 10 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Leptomeningeal disease-related neurological progression-free survival (LM-PFS) (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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01645839, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2019.