LUME-Lung 3. A Phase I/II study of continuous oral treatment with BIBF 1120 added to standard gemcitabine/cisplatin therapy in first line NSCLC patients with squamous cell histology.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death
globally with an estimated one million new cases diagnosed and 880,000 deaths
in the US each year. Histological subtypes of NSCLC respond differently to
chemotherapy treatment. NSCLC with squamous histology tended to have a better
response in a study where the antiangiogenic drug thalidomide was added to
chemotherapy. BIBF 1120 is an antiangiogenic drug in development in NSCLC and
ovarium carcinoma and has shown good tolerability. In this study, the efficacy
of addition of this investigational product to standard chemotherapy
(gemcitabine/cisplatin) is investigated.
As BIBF 1120 has never been tested with this chemotherapy combination, a run-in
phase I will be conducted to confirm safety and tolerability of doses of up to
200 mg BIBF 1120 b.i.d.
The thalidomide study seemed to indicate that the potential benefit was largely
seen in those patients who responded well to earlier treatments. Therefore, in
phase 2 of the LUME-Lung 3 study, BIBF 1120 will only be administered to
patients showing at least stable disease after 2 cycles of standard
chemotherapy.

Run-in phase I: To confirm the safety and tolerability of BIBF 1120 up to a
dose level of 200 mg b.i.d added to a standard dose of cisplatin/gemcitabine in
first line NSCLC patients with squamous cell histology. Pharmacokinetics of
BIBF 1120 and clinically relevant metabolites, gemcitabine and cisplatin.

Phase II: To investigate the efficacy and safety of BIBF 1120 compared to
placebo in first line NSCLC patients with squamous cell histology, and at least
stable disease after two cycles of cisplatin/gemcitabine chemotherapy.

Run-in phase I: Open-label, dose-confirmation study

Phase II: Two arm randomised placebo-controlled study of continuous BIBF 1120
added to cisplatin/gemcitabine. Patients who have had at least stable disease
after two cycles of cisplatin/gemcitabine treatment alone will be given up to 4
further cycles of cisplatin/gemcitabine chemotherapy with added BIBF
1120/placebo. After a total of 4 - 6 cycles of cisplatin/gemcitabine patients
will continue to receive BIBF 1120/placebo monotherapy as maintenance treatment
until disease progression, toxicity or withdrawal of consent.

Addition of BIBF 1120 to standard chemotherapy regimen with
cisplatin/gemcitabine, potentially followed by BIBF 1120 monotherapy.

This study investigates the addition of BIBF 1120 to standard chemotherapy. The
subjects have NSCLC with squamous histology, a diasese that is difficult to
treat and has limited options for therapy. BIBF 1120 has a favorable toxicity
profile and can potentially enhave survival of these patients.
The patient would undergo a number of the procedures required for this study
(blood draw, vital signs, CT scans) if he/she would receive chemotherapy,
regardless of study participation.
In phase I of this study, blood is drawn for pharmacokinetics. A financial
compensation is given, as this is an additional procedure and the subject has
to stay in the hospital for up to 8 hours.
In phase II of this study, blood may be drawn (about 10 ml) for retrospective
pharmacogenetic analysis. The subject can refuse participation in this testing,
but may continue to participate in the main study.