Etude de phase 1 évaluant le RAD001 en association avec la radiothérapie dans les cancers bronchiques non à petites cellules

RAD001 is known as a radiosensitizer. In this study we want to evaluatie the
tolerability of RAD001 (everolimus) when combined with radiotherapy in patients
with Non-small cell lung cancer, stage IIIA/B.

Primary objective: to evaluate the tolerability of the combination of RAD001
with radiotherapy.
Secondary objective(s) To determine the antitumor activity of the combination
of RAD001 (EVEROLIMUS) and radiotherapy (CR+PR+SD). To determine the
progression-free survival and the overall survival.

First phase of the study:
RAD001 (everolimus) will be administered per os every Monday, one week before
then during the radiotherapy and will be continued for 3.5 weeks after the end
of the radiotherapy. Chemotherapy is given 4.5 weeks after the end of
radiotherapy. Three patient cohorts are planned, receiving 10, 20 and 50 mg of
RAD001 per week.
Second phase of the study:
RAD001 (everolimus) will be administered per os every day one week before then
during the radiotherapy and will be continued for 3.5 weeks after the end of
radiotherapy. Chemotherapy is given 4.5 weeks after the end of radiotherapy.
Three patient cohorts are planned, receiving 2.5, 5 and 10 mg of RAD001 per day.
The two phases of the study may be conducted independently and in parallel.
Radiotherapy: 66 Grays over 6.5 weeks. (5 weekly fractions of 2 Grays)
Chemotherapy: 2 cycles: Cisplatin 100 mg/m2 D1, Navelbine 25 mg/m2 D1, D8,
every 21 days.

RAD001 in combination with standard radiotherapy.
Study treatments RAD001 (everolimus) combined with radiotherapy (66 Grays) and
followed by chemotherapy: dose escalation of RAD001 according to two regimens

1- RAD001 (everolimus) administered per os every Monday, one week before then
during the radiotherapy then for 3.5 weeks after the end of radiotherapy. Three
patient cohorts are planned, receiving 10, 20 and 50 mg per week.

2- RAD001 (everolimus) will be administered per os every day one week before
then during the radiotherapy then for 3.5 weeks after the end of radiotherapy.
Three patient cohorts are planned, receiving 2.5, 5 and 10 mg per week.
Number of patients Calculation of the number of subjects required:
30

the burden associated with participation in this trial is not totally different
from standart treatment with chemoradiation. After screening patients will be
seen every week by their radiation-oncologist to check for complaints related
to the radiotherapy or related to the study medication. The only extra
examination will be a weekly electrocardiogram. Since this is a phase I trial
we don't know the side effects. From the experience with RAD001 alone mild side
effects can be expected such as fatique, nausea and/or vomiting, mouth ulcers,
skin rash and headache. A few cases of moderate non-infectious pulmonary
toxicity have been reported. It is usually of moderate intensity and regresses
on withdrawal of the treatment. In less then 1 % a severe form has been
reported. Therefore the physician will carefully watch for unusual respiratory
symptoms such as sudden onset of breathing difficulties, cough or fever.



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