An Open-label, Multi-center, Phase II Study to Evaluate the Activity of Patupilone (EPO906), in the Treatment of Recurrent or Progressive Brain Metastases in Patients With Non-small Cell Lung Cancer.
- World Health Organization (WHO) performance status of 0, 1 or 2 (corresponding to
Karnofsky performance status of 50 or better)
- Patients with radiologically proven (by gadolinium-enhanced [Gd-] magnetic resonance
imaging [MRI]) parenchymal brain metastases from histologically confirmed non-small
cell lung cancer (the primary disease may be quiescent). Gd-MRI must be performed
within 2 weeks of study entry.
- Patients should have at least one bidimensionally measurable intracranial lesion of a
minimum of 2 cm as defined by Gd-MRI. If the patient has had previous radiation to
the marker lesion(s), there must be evidence of residual disease > 2 cm or the lesion
must have demonstrated progression since the radiation.
- Those patients progressing on radiotherapy must have a 25% increase in the size of
the previously radiated intracranial lesion based on the Neuro-Oncology Criteria of
Tumor Response for Central Nervous System (CNS) Tumors or appearance of new lesions.
- Patients must be controlled on medication and neurologically stable: stable on
steroids and anticonvulsants for at least 2 weeks prior to obtaining the baseline
Gd-MRI of the brain, and/or at least 2 weeks prior to beginning study treatment.
- Female patients must have a negative serum pregnancy test at screening. (Not
applicable to patients with bilateral oophorectomy and/or hysterectomy or to those
patients who are postmenopausal.)
- All patients of reproductive potential must agree to use an effective method of
contraception during the study and for three months following termination of
- Written informed consent must be obtained.
- Clinical evidence of leptomeningeal disease
- Patients with extracranial disease in more than 3 organ sites including the primary
- Patients who have received any investigational compound within the past 28 days or
who are planning to receive other investigational drugs while participating in the
- Prior administration of epothilone(s)
- Patients with peripheral neuropathy > grade 1
- Patients with unresolved diarrhea within the last 7 days before treatment.
- Patients receiving known diarrheogenic agents must stop treatment with these agents
prior to enrollment in the study.
- Radiotherapy < 3 weeks prior to study entry
- Prior intracranial surgery < 3 weeks prior to study entry; patient must have
recovered from surgery prior to study entry.
- Chemotherapy < 3 weeks prior to study entry; < 6 weeks from prior nitrosoureas.
- Severe cardiac insufficiency (New York Heart Association [NYHA] III or IV), with
uncontrolled and/or unstable cardiac or coronary artery disease
- Radiotherapy not permitted while on study. Exception: palliative radiotherapy of
metastasis in extremities is allowed, but such lesions cannot be used as target or
- Patients receiving hematopoietic growth factors except for erythropoietin
- Patients taking Coumadin® or other agents containing warfarin, with the exception of
low dose Coumadin® (1 mg or less daily) administered prophylactically for maintenance
of in-dwelling lines or ports