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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Status: Withdrawn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 malignancies

To 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

Page last updated: August 23, 2015

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