Study of Everolimus in the Treatment of Advanced Malignancies in Patients With Peutz-Jeghers Syndrome
Information source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Peutz-Jeghers Syndrome; Neoplastic Processes; Neoplasm Metastasis
Intervention: Everolimus (Drug)
Phase: Phase 2
Status: Withdrawn
Sponsored by: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Official(s) and/or principal investigator(s): Heinz-Josef Klumpen, MD, Principal Investigator, Affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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.
Clinical Details
Official title: Pilot Study of Everolimus in the Treatment of Neoplasms in Patients With Peutz-Jeghers Syndrome
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: To determine the response rate of Everolimus in patients with advanced cancer and PJS.
Secondary outcome: To determine the overall survival of PJS patients treated with everolimus for advanced malignanciesTo determine the time to progression of PJS patients treated with everolimus for advanced malignancies. To determine the safety and toxicity of Everolimus in this patient population To determine if there is an association between measured drug blood levels and treatment outcome measured as response to treatment determined by RECIST 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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Academic Medical Center, Amsterdam 1105AZ, Netherlands
Erasmus Medical Center, Rotterdam 3000 CA, Netherlands
Additional Information
Starting date: October 2010
Last updated: April 21, 2015
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