Inclusion Criteria

Tow cohorts of PJS patients will be included. Cohort 1: Advanced malignancy Cohort 2: High
risk polyps

General inclusion criteria:

1. Known Peutz-Jeghers disease (with LKB1 mutation)

2. No concurrent systemic anti cancer treatment

3. No prior treatment with m-TOR inhibitor

4. Prior malignancies or concurrent second malignancies are allowed

5. Prior systemic therapy is permitted with a washout time of at least 4 weeks

6. ECOG/ WHO performance 0-2

7. Age > 18 years

8. Adequate renal function (defined as creatinine < 150 μmol/L)

9. Adequate liver function (bilirubin < 1.5 times upper limit of normal, ALAT or ASAT <
5.0 times upper limit of normal in case of liver metastases and < 2.5 the upper limit
of normal in absence of liver metastases

10. Adequate bone marrow function (WBC > 3.0 x 10 9/L, platelets > 100 x 10 9/L)

11. Absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule;
those conditions should be discussed with the patient before registration in the
trial.

12. No pregnancy or lactating and ifof childbearing potential patients must agree to use
a reliable contraceptive method throughout the study

13. No serious concomitant systemic disorder that would compromise the safety of the
patient,at the discretion of the investigator

14. Signed informed consent according to ICH/GCP.

15. No uncontrolled symptomatic hyperglycaemia

Specific inclusion criteria for cohort 1:

1. Cytological or histological confirmed carcinoma

2. Metastatic or non-resectable disease

3. Patients with clinically and/or radiographically documented measurable lesion
according to

RECIST criteria:

1. X-ray, physical exam > 20 mm

2. Spiral CT scan > 10 mm

3. Non-spiral CT scan > 20 mm

Specific inclusion criteria for cohort 2:

1. Known high risk polyps (definition see page 19)

2. Ability to undergo endoscopies

Specific Exclusion criteria:

Symptomatic PJ-polyps, defined as polyps likely to be responsible/causal for the abdominal
symptoms the patient presents with.