Pilot study of everolimus in the treatment of advanced malignancies in patients with Peutz-Jeghers syndrome

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

Two cohorts of PJS patients will be included.
Cohort 1: Advanced malignancy
Cohort 2: High risk polyps
*Known Peutz-Jeghers disease (with LKB1 mutation)
*Advanced malignancy of any tumor type, not suitable for surgery at the time of study enter
*No concurrent systemic anti cancer treatment
*No prior treatment with m-TOR inhibitor
*Prior malignancies or concurrent second malignancies are allowed
*Prior systemic therapy is permitted with a washout time of at least 4 weeks
*Cytological or histological confirmed carcinoma
*Metastatic or non-resectable disease
*Patients with clinically and/or radiographically documented measurable lesion according to RECIST criteria: X-ray, physical exam > 20 mm; Spiral CT scan > 10 mm; Non-spiral CT scan > 20 mm
*ECOG/ WHO performance 0-2
*Age > 18 years
*Life expectancy > 3 months
*Adequate renal function (defined as creatinine < 150 *mol/L)
*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
*Adequate bone marrow function (WBC > 3.0 x 10 9/L, platelets > 100 x 10 9/L) E.
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:
a. X-ray, physical exam > 20 mm
b. Spiral CT scan > 10 mm
c. 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

Exclusion Criteria

*Presence 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
*Patients who are pregnant or lactating
*Patients who are of childbearing potential who do not agree to use a reliable contraceptive method throughout the study
*Patients who do have serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator
*Patients who are not willing to sign the Signed informed consent according to ICH/GCP, IRB approval obtained prior to treatment
*Patients who do have uncontrolled symptomatic hyperglycaemia
* Symptomatic PJ-polyps, defined as polyps likely to be responsible/causal for the abdominal
symptoms the patient presents with.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p> To determine the efficacy(as measured by objective tumor response) of single<br /><br>agent everolimus in the treatment of advanced malignancies or high risk polyps<br /><br>of patients known with PJS </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>To determine the overall survival of patients treated with everolimus in<br /><br>patients with advanced malignancies in PJS.<br /><br>To evaluate the time to progression<br /><br>To evaluate the toxicity profile of everolimus in PJS patients<br /><br>To determine the association between drug levels of everolimus and objective<br /><br>clinical response<br /><br>*To determine the influence of everolimus on the proliferation signaling mTOR<br /><br>pathway and its downstream targets in the tumor and blood prior and during<br /><br>treatment with the use of established biomarkers. </p><br>

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