Double blind randomized phase III study of maintenance Pazopanib versus placebo in NSCLC patients non progressive after first line chemotherapy. MAPPING, an EORTC
Lung group study.

Traditionally patients with NSCLC are given chemotherapy for a set number of
courses (4 months). The median survival of this treatment is 10 months.
However there is new interest in starting a different treatment after the
course to chemotherapy to prolong remission and improve survival. There are 2
drugs which have been tested and are now licensed in this setting.
Pemetrexed (Alimta) is an intravenous chemotherapy which has been shown to be
useful in patients who
did not initially receive this drug and who have a subtype of lung cancer
called 'adenocarcinoma'. Erlotinib
(Tarceva) is a tablet form of treatment that has been shown to help patients
who have had 'stable disease'
i.e. no tumor shrinkage after initial chemotherapy. The relative advantage of
these treatments is small in
terms of time and they both have side effects. In addition overall they have
not been proven to be better
than receiving the treatments when the disease flares up at a later point.
However the real disadvantage of
these treatments is that they are only applicable for certain subgroups of
patients and better treatments are
needed.
Pazopanib has now been approved by the U.S. Food and Drug Administration FDA
for the treatment of
patients with advanced renal (kidney) cell carcinoma. Pazopanib has recently
demonstrated single agent
activity in early-stage lung cancer (pre-surgery).

To compare the therapeutic benefit of maintenance pazopanib versus placebo
after first line treatment of NSCLC.

This is a randomized, multi-centre, double blind placebo-controlled integrated
phase II/III study. Patients will be randomized 1:1 into two treatment arms,
allowing comparison between placebo and maintenance treatment with pazopanib.

Treatment with pazopanib or placebo. Pazopanib or placebo will be given at a
dose of 600 mg daily for the first two weeks and then at a daily dose of 800 mg
if well tolerated or at 400 mg if toxicity occurred. Pazopanib or placebo will
be given orally daily until disease progression.

Risks: Side effects of pazopanib.
Burden: the extent of the burden for the patient is less. A lot of tests which
the patient should have undergone are common practise, but more frequently done.
Total of visits: Screening (1), study treatment: variable time, after first 2
weeks at 600 mg, each 4 weeks, end of treatment visit (1) . Follow-up visits:
first year every 3 months, thereafter every 6 months.
Physical examination (Performance Status, BP, toxicity assessment) and
bloodtests will be done at screening, after first 2 weeks at 600 mg, every 4
weeks during study treatment and at end off-treatment, thereafter during every
visit in the follow-up (the bloodpressure, hematology and chemistry will be
checked every week during the first cycle.
CT-scan/MRI (respons evaluation) will be done at screening and at 6, 14 and 22
weeks and additional scans as per institutional guidelines.
CRP and QoL (QLQ-C30 and QLQ-LC13) and EQ-5D will be done at screening and at
week 6, 14 en 22.
ECG will be done at screening, after first 2 weeks at 600 mg and at week 6,14
en 22 and then every 2 cycles.
EGFR mutation (by IHC) will be tested at screening.