Clinical and Pharmacological Study With 2B3-101 in Patients With Breast Cancer and Leptomeningeal Metastases

NCT01818713 | Unknown Phase 2

• 1 other identifier: N12LMB
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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 with up to 25% long-term survivors. Many potentially highly efficacious intravenous chemotherapies are currently not effective to treat LM because they do not adequately cross the blood-CSF barrier. Doxorubicin, the anthracycline chemotherapeutic agent, has a well-established antineoplastic activity in breast cancer. To optimally enhance the delivery of liposomal doxorubicin to the brain, to-BBB technologies B.V. has designed a glutathione (GSH) pegylated liposomal doxorubicin hydrochloride formulation (2B3-101). Coating of liposomes with PEG ensures the prolonged circulation time in plasma, whilst conjugation of GSH to the tips of the PEG molecules targets the liposomes towards the active GSH transporters on the BBB to enhance the delivery of doxorubicin to the brain. This is a a clinical and pharmacological study that aims to determine preliminary efficacy of treatment with 2B3-101 in patients with leptomeningeal metastases of breast cancer using the LM response score.

Conditions

Meningeal Carcinomatosis

Keywords

2B3-101, liposomal doxorubicin, leptomeningeal metastases

Outcome Measures

Primary Outcomes (1)

• - safety and preliminary response using the "LM response score" during the 2B3-101 treatment in patients with LM from breast cancer.

  All adverse events will be collected during the safety visits and summarized during the analysis using descriptive statistics. The data reported every 2 cycles by de radiologist (MRI reports), pathologist (CSF cytology) and neurologist (clinical response) will be compared using specially designed "LM response score" for this study.

  one year

Secondary Outcomes (6)

• - CNS progression free survival in patients with LM from breast cancer treated with 2B3-101.

  one year

• - collecting clinical and radiological findings (MRI) and CSF cytology and comparing them with doxorubicin levels in CSF and in plasma during the treatment of patients with LM from breast cancer with 2B3-101.

  one year

• - systemic progression free survival in patients with LM from breast cancer treated with 2B3-101.

  one year

• overall survival in patients with LM from breast cancer treated with 2B3-101.

  one year

• - the change in number of CTCs in CSF and blood and its correlation with the LM response score.

  one year

Study Arms (1)

2B3-101

EXPERIMENTAL

A single dose of 2B3-101 (a glutathione (GSH) pegylated liposomal doxorubicin hydrochloride formulation) will be administrated intravenously once per cycle. To minimize the risk of infusion reactions, 5% of the total dose of 2B3-101 (in mg) will be administrated over the first 30 minutes. If tolerated, the infusion may then be completed over the next hour for a total infusion time of 90 minutes

Drug: 2B3-101

Interventions

2B3-101 DRUG

50 mg/m2 2B3-101 intravenous 3-weekly administration

Also known as: glutathione pegylated liposomal doxorubicin

2B3-101

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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);

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (1)

the Netherlands Cancer Institute - Antoni van Leeuwenhoek

Amsterdam, 1066CX, Netherlands

RECRUITING

MeSH Terms

Conditions

Meningeal Carcinomatosis

Interventions

glutathione pegylated liposomal doxorubicin

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Officials

• D. Brandsma, MD, PhD

  NKI-AvL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

D. Brandsma, MD, PhD

CONTACT

+31205122570; d.brandsma@nki.nl

B. Milojkovic Kerklaan, MD

CONTACT

bo.milojkovic@nki.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: March 18, 2013
• First Posted: March 26, 2013
• Study Start: October 1, 2013
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: October 29, 2013

Record last verified: 2013-10

Locations

NL (1)