Clinical trial NCT01178151: Study of Everolimus in the Treatment of Advanced Malignancies in Patients With Peutz-Jeghers Syndrome
Official title: Pilot Study of Everolimus in the Treatment of Neoplasms in Patients With Peutz-Jeghers Syndrome
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Peutz-Jeghers Syndrome
Neoplastic Processes
Neoplasm Metastasis
Keywords: Peutz-Jeghers syndrome
mTOR inhibition
cancer
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
First posted: 2010-08-10
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this pilot study the investigators will treat all patients known with Peutz-Jeghers syndrome (PJS) who are diagnosed with advanced malignancies with everolimus 10mg daily until disease progression. Most patients with PJS have an inherited LKB1 mutation leading to aberrant m-TOR activity. Their risk to develop malignancies or intestinal polyps is probably related to this constitutive mTOR signaling. The hypothesis is that mTOR inhibition is an effective anticancer treatment in PJS patients with advanced malignancies.


Eligibility 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.

Primary outcomes:
measure: To determine the response rate of Everolimus in patients with advanced cancer and PJS.
timeFrame: During treatment, expected avarage of 12 months
Secondary outcomes:
measure: To determine the overall survival of PJS patients treated with everolimus for advanced malignancies
timeFrame: avarage of 18 months
measure: To determine the time to progression of PJS patients treated with everolimus for advanced malignancies.
timeFrame: During treatment, expected avarage of 12 months
measure: To determine the safety and toxicity of Everolimus in this patient population
timeFrame: During treatment, expected avarage of 12 months
measure: To determine if there is an association between measured drug blood levels and treatment outcome measured as response to treatment determined by RECIST
timeFrame: During treatment, expected avarage of 12 months
measure: To assess markers for activated mTOR pathway (including phospho-S6 and phospho-4E BP1) in all pre-treatment tissue specimens and collected specimens during treatment and correlate with response to treatment.
timeFrame: During treatment, expected avarage of 12 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Heinz-Josef Klumpen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Brabander J, Eskens FALM, Korsse SE, Dekker E, Dewint P, van Leerdam ME, van Eeden S, Klumpen HJ. Chemoprevention in Patients with Peutz-Jeghers Syndrome: Lessons Learned. Oncologist. 2018 Apr;23(4):399-e33. doi: 10.1634/theoncologist.2017-0682. Epub 2018 Jan 25.