An Open Label, Phase I/II Dose Escalating Study Evaluating the Safety and Efficacy of EPO906, qw3, in Patients With Non-small Cell Lung Cancer.
- Patients with histologic or cytologic confirmation of unresectable locally advanced
or metastatic NSCLC (stage IIIB with pleural effusion only / stage IV) documented
before first line therapy.
- Prior treatment with a platinum-containing regimen
- Age ≥18 years.
- Performance status of 0-1 on the WHO scale.
- Life expectancy of ≥3 months.
- NSCLC patients should have at least one measurable lesion as defined by modified
RECIST criteria. If the patient has had previous radiation to the marker lesion(s),
the lesion must have demonstrated progression since the radiation.
- NSCLC patients with controlled brain metastases are eligible to be enrolled in the
brain metastases cohort at the MTD. "Controlled brain metastases" patients are
defined as patients who are neurologically stable, i.e. have not experienced an
increase in dose of steroidal or anticonvulsive therapy for at least 14 days prior to
- Patients with brain metastases must be verified to have metastases secondary to NSCLC
based on histology of primary and by temporal sequence of events (note: these
patients are eligible even if lung disease is quiescent).
- Patients with brain metastases must show evidence of residual disease or progression
of disease since prior radiological or surgical therapy.
- Patients with brain metastases should have at least one bidimensionally measurable
intracranial lesion of minimum diameter 2 cm. Multifocal disease is permitted, but
the eligibility of BM patients presenting with more than 6 intracranial lesions
should be discussed with Novartis prior to enrolling the patient.
- Patients with adequate hematologic parameters:
- ANC ≥1.5 x 10^9/L;
- Hb ≥9.0 g/dL,
- Platelet count ≥100 x 10^9/L (untransfused).
- Demonstrate the following blood chemistry laboratory values:
- total bilirubin ≤ 1.5 x ULN;
- AST/ALT ≤ 2.5 X ULN; (≤ 5 x ULN if hepatic metastasis is present)
- alkaline phosphatase ≤ 2.5 x ULN; (≤ 5 x ULN if hepatic and/or bone metastasis are
- serum creatinine < 2 x ULN.
- 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 three months following termination of treatment.
- All patients must use a barrier method for contraception for sexual intercourse or
avoid this for the first 5 days after patupilone infusion.
- Written informed consent must be obtained.
- Patients who have received more than one prior chemotherapy regimen or any other
systemic antineoplastic treatment including immunotherapy.
- 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
- Patients with brain metastases who have received any prior chemotherapy regimen or
any other systemic antineoplastic treatment for brain metastases.
- Patients with brain metastases who have experienced a dose increase of 25% or more
above previous dose, in concomitant steroidal or anticonvulsive therapy within 14
days prior to study entry.
- Patients with brain metastases receiving steroidal or anticonvulsive therapy for whom
a dose increase has been required within 14 days prior to start of study drug.
- Patients with brain metastases who have leptomeningeal disease.
- Patients with brain metastases who have extracranial metastases in more than two
- Patients with any peripheral polyneuropathy > Grade 1.
- Patients with unresolved diarrhea > Grade 1.
- Patients receiving hematopoietic growth factors except erythropoietin (refer Section
- Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable
cardiac or coronary artery disease.
- Patients taking warfarin or other agents containing warfarin, with the exception of
low dose warfarin (1 mg or less daily) administered prophylactically for maintenance
of in-dwelling lines or ports.
- Patients who have not recovered fully from surgery for any cause, including brain
metastases patients who have had a biopsy or surgical resection of the brain tumor
within 2 weeks prior to starting study drug or who are not fully recovered from any
prior biopsy or surgical resection.
- Patients who have received radiation therapy or chemotherapy within the last four
weeks. Palliative radiotherapy of metastasis in extremities is allowed but such
lesions cannot be used as tumor markers.
- Patients with the presence of active or suspected acute or chronic uncontrolled
infection, including abscess or fistulae.
- Patients known to be HIV positive.
- History of another malignancy within 3 years prior to study entry, except curatively
treated non-melanotic skin cancer or cervical cancer in situ.
- For patients enrolling in the brain metastases cohort, any of the following
exclusions to MRI imaging:
Cardiac pacemaker Ferromagnetic metal implants other than those approved as safe for use
in MRI scanners Claustrophobia Obesity (exceeding the limits of scanning equipment)
- Pregnant or lactating females.
- A history of noncompliance to medical regimens or inability or unwillingness to
return for all scheduled visits.
Other protocol-dependent inclusion / exclusion criteria may apply