Status:
UNKNOWN
Clinical and Pharmacological Study With 2B3-101 in Patients With Breast Cancer and Leptomeningeal Metastases
Lead Sponsor:
The Netherlands Cancer Institute
Conditions:
Meningeal Carcinomatosis
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief Summary
Leptomeningeal metastases (LM) develop when tumor cells reach the cerebrospinal fluid (CSF) and infiltrate the leptomeninges. The median survival of patient with breast cancer and LM is 4-6 months wit...
Detailed Description
Leptomeningeal metastases (LM) develop when tumor cells reach the cerebrospinal fluid (CSF) and infiltrate the leptomeninges. Clinically symptomatic LM affects approximately 5 percent of patients with...
Eligibility Criteria
Inclusion
- Inclusion criteria:
- Age ≥ 18 years.
- Radiological or cytological evidence of clinically LM of pathologically confirmed breast cancer.
- Concomitant brain metastases are allowed
- ECOG Performance Status ≤ 2.
- Estimated life expectancy of at least 8 weeks.
- Stable/decreasing dosage of steroids (e.g.dexamethasone) for 7 days prior to baseline MRI.
- Use of non-enzyme inducing anti-epileptic drugs is allowed.
- Toxicities incurred as a result of previous anticancer therapy (radiation therapy, chemotherapy, or surgery) must be resolved to ≤ grade 2 (as defined by CTCAE version 4.0).
- Written informed consent according to local guidelines.
- Local radiation of CNS symptomatic sites more than four weeks prior to start of the study is allowed.
- Exclusion criteria:
- Less than 4 weeks from the last treatment of chemotherapy, biological therapy, immunotherapy, endocrine therapy and less than 6 weeks for nitrosoureas and mitomycin C.
- Less than 4 weeks from the last radiotherapy of the brain or spinal cord/cauda equine.
- Patients that have received a maximum cumulative dose of free (i.e., non-liposomal) or liposomal doxorubicin \> 360mg/m2 or free epirubicin \> 600mg/m2
- Current or recent (less than 4 weeks before first 2B3-101 treatment) treatment with another investigational drug.
- Any other current anticancer therapy
- Inadequate bone marrow function, defined as: Absolute Neutrophil Count (ANC): \< 1.5 x 109/L, or platelet count \< 100 x 109/L or haemoglobin \< 6 mmol/L.
- Inadequate liver function
- Inadequate renal function
- Pregnancy or lactation
- For female subjects of childbearing potential (defined as \< 2 years after last menstruation and not surgically sterile) and male subjects who are not surgically sterile and with female partners of childbearing potential: absence of effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal gel).
- Major surgical procedure (including open biopsy, excluding central line IV and Port-a-cath) within 4 weeks prior to the first study treatment, or anticipation of the need for major surgery during the course of the study treatment.
- Grade 3 or 4 motor, sensory, or cranial neuropathy symptoms (as defined by CTCAE version 4.0) caused by previous chemotherapy.
- Uncontrolled hypertension (systolic \> 150 mm Hg and/or diastolic \>100mm Hg).
- Clinically significant (i.e. active) cardiovascular disease defined as:
- Stroke within 6 months prior to treatment with 2B3-101 (day 1);
- Transient Ischaemic Attack (TIA) within 6 months prior to day 1;
- Myocardial infarction (MI) within ≤ 6 months prior to day 1;
- Unstable angina pectoris (AP);
- New York Heart Association (NYHA) Grade II or greater Congestive Heart Failure (CHF);
- Cardiac arrhythmia, except stable atrium fibrillations;
- LVEF by MUGA or ECHO \< 50%.
- Known hypersensitivity to any of the study drug components or its excipients (doxorubicin, PEG or GSH).
- Evidence of any other medical conditions that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.
- Contra-indications for lumbar punctures:
- blood clotting disorders (INR\>1.5, platelets \<20x109 /l, aPTT \> 1.5 ULN). Lumbar puncture after platelets transfusion resulting into platelets \> 20x109 /l after transfusion is allowed.
- therapeutic anticoagulant treatment that cannot be interrupted for 24 hours. Low dose prophylactic treatment with low molecular weight heparins is allowed.
- cerebral space-occupying lesions with a risk of cerebral herniation.
- spinal space-occupying lesions with a risk of myelocompression or conus/cauda compression.
- Active systemic or CNS infection.
Exclusion
Key Trial Info
Start Date :
October 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
October 1 2014
Estimated Enrollment :
6 Patients enrolled
Trial Details
Trial ID
NCT01818713
Start Date
October 1 2013
End Date
October 1 2014
Last Update
October 29 2013
Active Locations (1)
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1
the Netherlands Cancer Institute - Antoni van Leeuwenhoek
Amsterdam, Netherlands, 1066CX