Cilengitide (EMD121974) in Combination With Whole Brain Radiotherapy in Patients With Brain Metastases From Lung Cancer - a Single-center, Open-label Phase I Study
18 Years
N/A
Both
Brain and Central Nervous System Tumors, Lung Cancer
Trial Information
Cilengitide (EMD121974) in Combination With Whole Brain Radiotherapy in Patients With Brain Metastases From Lung Cancer - a Single-center, Open-label Phase I Study
OBJECTIVES:
- Primary
- To assess the safety and tolerability of daily cilengitide by determining its
dose-limiting toxicity and maximum-tolerated dose when combined with concomitant
fractionated whole-brain radiation therapy in patients with brain metastases from
lung cancer.
- Secondary
- To collect evidence of the best overall response rate, overall survival,
brain-specific progression-free survival, and tumor-specific progression-free
survival of these patients.
- To collect evidence of changes in functional MRI imaging studies at 6 and 12 weeks
after initiation of therapy.
- To collect evidence of early response by functional MRI (ASL technique) on days 1,
4, and 12, immediately before and after the administration of cilengitide.
- To collect evidence of changes in neurological and neurocognitive function tests
at 6 and 12 weeks after initiation of therapy.
- To further evaluate the safety and toxicity of the combination of cilengitide and
whole-brain radiation therapy.
- To further evaluate the pharmacokinetics of cilengitide administered daily.
OUTLINE:
Patients receive oral cilengitide once daily and undergo whole-brain radiotherapy on the
same days. Treatment continues for 2 weeks in the absence of disease progression or
unacceptable toxicity.
Patients undergo blood sample collection on days 1, 4, 5, and 12 for pharmacokinetic
studies.
After completion of study treatment, patients are followed for 10 weeks.
Inclusion Criteria:
DISEASE CHARACTERISTICS:
- Histologically confirmed lung cancer (small cell or non-small cell lung cancer)
- Patient must be eligible for whole-brain radiotherapy
- Presence of brain metastasis (single or multiple, synchronous or metachronous) from
lung cancer not amenable to surgery or radiosurgery (presence of metastases at any
other site is allowed)
- No leptomeningeal metastasis or known subarachnoid spread of tumor
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-1 (ECOG PS 2 allowed if due to the presence of
cerebral metastases and not due to a high peripheral-tumor load or other reasons)
- Life expectancy ≥ 3 months
- Adequate hematologic function
- Total bilirubin < 1.5 times upper limit of normal (ULN)
- AST, ALT, and alkaline phosphatase < 2.5 times ULN
- Creatinine clearance > 60 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after
completion of study treatment
- No history of acute or chronic renal disease
- No other malignancies treated within the past 5 years, except adequately treated
carcinoma in situ of the cervix or basal cell carcinoma of the skin
- No uncontrolled hypertension
- No history of coagulation disorder associated with bleeding or recurrent thrombotic
events
- No peptic ulcer disease within the past 6 months
- No congestive heart failure, high risk for uncontrolled arrhythmia, or history of
clinically significant coronary heart disease
- No known alcohol or drug abuse
- No other significant or acute concomitant disease
- No dementia or altered mental status
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Concurrent corticosteroids allowed if the dosing regimen has ben stable ≥ 5 days
- Concurrent anticonvulsants allowed if the dosing regimen has been stable for the past
week
- More than 30 days since prior participation in another clinical trial
- No concurrent anticoagulation with vitamin K antagonists, therapeutic-dose
anticoagulation with heparin resulting in prolonged PTT, or therapeutic-dose
anticoagulation with low molecular weight heparin (low-dose [i.e. prophylactic], low
molecular weight heparins allowed)
- No prior whole-brain radiation or radiosurgery
- No prior antiangiogenic therapy
- No other concurrent anticancer therapy
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Dose-limiting toxicity
Safety Issue:
Yes
Principal Investigator
Christian Manegold, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
University Medical Center Mannheim
Authority:
Germany: Federal Institute for Drugs and Medical Devices
Study ID:
CDR0000636508
NCT ID:
NCT00884598
Start Date:
December 2008
Completion Date:
December 2011
Related Keywords:
- Brain and Central Nervous System Tumors
- Lung Cancer
- adult tumors metastatic to brain
- extensive stage small cell lung cancer
- stage IV non-small cell lung cancer
- Lung Neoplasms
- Neoplasm Metastasis
- Nervous System Neoplasms
- Central Nervous System Neoplasms
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