A Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination with Docetaxel, Compared with Placebo in Combination with Docetaxel, in Patients receiving second line treatment for Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB-IV)

Patients with advanced non-small cell lung cancer (NSCLC) have a very poor
prognosis. Therefore, there is a strong medical need for medicines that have
more benefit for the patient than the current standard treatment.
Selumetinib works by blocking the action of a protein, that controls cell
growth. This protein (MEK) is activated by another protein called KRAS.
Blocking MEK may lead to an improvement in response to treatment with docetaxel
when givenb with selumetinib, compared to when docetaxel is given alone. Rcent
published research showed that drugs that are blocking MEK appears to increase
the activity if combined with other anticancer medicines compared to when
chemotherapy is given alone, in both tumours with and without KRAS mutation.
This study will include patients that will not have a KRAS mutation seen in
tumour samples.
Further studies are necessary to assess the efficacy and safety of Selumitinib
in combination with docetaxel in patients with KRAS mutation- negative NSCLC.

To assess the efficacy, measured as progression free survival, and safety of
Selumetinib in combination with docetaxel, compared to docetaxel alone, in
patients receiving second line treatment for KRAS mutation negative locally
advanced or metastatic non small cell lung cancer.

Phase II, double-blind, randomised, placebo-controlled study
Randomised in a ratio of 2:2:1
- Selumetinib (75 mg dd on every day of a cycle of 21 days) in combination with
75 mg/m2 docetaxel (given on day 1 of every 21 day cycle)
- Selumetinib (75 mg dd on every day of a cycle of 21 days) in combination with
60 mg/m2 docetaxel (given on day 1 of every 21 day cycle)
- Placebo in combination with 75 mg/m2 docetaxel (given on day 1 of every 21
day cycle)

Patient will be dosed twicedaily with a oral dose (capsules) of Selumetinib or
placebo in combination with 75 mg/m2 of 60 mg/m2 docetaxel iv, administered on
day 1 of each 21 day cycle.

On several days during the study patients will undergo the following
assessments:
- anamnesis (at screening also medical history)
- physical examination
- vital signs (blood pressure, pulse)
- length
- weight
- CT or MRI scan
- ECG
- eye assessment
- blood and urine assessments
- MUGA/echocardiogram
- questionnaires (LSCC (specific voor lung cancer symptoms) en SF-36v2)
- diary card
- pregnancy test
- tumor biopsy (optional)

Adverse events of Selumetinib (AZD6244), docetaxel or the combination:
Adverse events that may be caused by Selumetinib are: rash, dry skin, nail
changes, fever, stomatitis, diarrhea, nausea, vomiting, swelling of the face or
extremities, shortness of breath, fatigue, increase in blood pressure, blurring
of vision, increase in phosphate level, increase in some liver proteins, low
albumin level, decrease in the pumping performance of the heart,
Adverse events, that probably may be caused by selumetinib are: weakness of
neck muscles, cough, eye problems, increase in blood level of CPK.
The most common side effects that may be caused by docetaxel are: decrease in
number of white blood cells, rash, diarrhea, nausea, vomiting, hair loss,
tiredness, burning or tingling sensation in hands or feet, muscle pain,
elevated tear production, allergic reaction and nail changes.
When selumetinib was used in combination with docetaxel, the number of patients
with side effects, and or the severity of side effects was increased.
Female patients cannot become pregnant during this study.