An Open-label, Multi-center, Non-randomized Phase Ib Study to Investigate the Safety, Efficacy, and Pharmacokinetics of BAY 73-4506 "Regorafenib", Administered in Combination With Pemetrexed and Cisplatin in Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer
Inclusion Criteria:
- Age >= 18 years.
- Histological or cytological diagnosis of metastatic Stage IV or locally advanced,
unresectable confirmed Stage IIIB nonsquamous Non-Small Cell Lung Cancer (NSCLC) not
amenable to local therapy with curative intent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2
- Life expectancy of at least 12 weeks.
- Adequate bone marrow, liver, and renal function
- Controlled blood pressure [defined as systolic Blood Pressure (BP) <=150 mmHg and
diastolic Blood Pressure (BP) <= 90 mmHg]
- Men and women of childbearing potential enrolled in this study must use adequate
barrier birth control measures during the course of the study
Exclusion Criteria:
- Sensory neuropathy with sensory alterations or paresthesia (including tingling),
interfering with function
- Hearing impairment
- Persistent proteinuria of Common Toxicity Criteria (CTC) Grade 3 or higher
- Cardiac disease: congestive heart failure > New York Heart Association (NYHA) Class
II; patients must not have unstable angina (anginal symptoms at rest) or new-onset
angina (began within the last 3 months) or myocardial infarction within the past 6
months; cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- Brain metastasis: patients with neurological symptoms should undergo a Computerized
Tomography (CT) scan / Magnetic Resonance Imaging (MRI) of the brain to exclude any
new or progressive brain metastasis. Patients with brain metastases are excluded
from the trial
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident
(including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
within the 6 months before start of study medication
- Pulmonary hemorrhage/bleeding event > Common Terminology Criteria for Adverse Events
(CTCAE) Grade 2 within 4 weeks prior to the start of study treatment. Clinically
significant hemoptysis (1 teaspoon or more) in the past 3 months
- Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks prior to the start
of study treatment
- Evidence or history of bleeding diathesis or coagulopathy
- Centrally located tumors with radiologic evidence (CT or MRI) of local invasion of
major blood vessels
- The effect of third space fluid, such as pleural effusion and ascites, on pemetrexed
is unknown. In patients with clinically significant third space fluid, consideration
should be given to draining the effusion prior to study start
- Patients with phaeochromocytoma Excluded Therapies and Medications, Previous and
Concomitant
- Prior treatment with a systemic chemotherapy for metastatic NSCLC. Patients who
underwent prior systemic treatment or radiotherapy for NSCLC in a neoadjuvant or
adjuvant setting are eligible, but no chemotherapy treatment within the last 6 month
prior to study entry is allowed