Study of Everolimus in the Treatment of Advanced Malignancies in Patients With Peutz-Jeghers Syndrome

Phase 2

Withdrawn

• Conditions: Peutz-Jeghers Syndrome; Neoplasm Metastasis; Neoplastic Processes
• Interventions: Drug: Everolimus

• Registration Number: NCT01178151
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-07-26
• Study First Submitted QC: 2010-08-09
• Study First Posted: 2010-08-10
• Study Start: 2010-10
• Status Verified: 2015-04
• Primary Completion: 2015-04
• Study Completion: 2015-04
• Last Update Submitted: 2015-04-21
• Last Update Posted: 2015-04-22

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
afinitor	Everolimus	10mg afinitor daily orally

Primary Outcome Measures

Name	Time	Method
To determine the response rate of Everolimus in patients with advanced cancer and PJS.	During treatment, expected avarage of 12 months	Determined with regular radiological scans once every 9 weeks and measured following RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
To determine the overall survival of PJS patients treated with everolimus for advanced malignancies	avarage of 18 months	The time between date of entering the study and date of death will be collected.
To determine the time to progression of PJS patients treated with everolimus for advanced malignancies.	During treatment, expected avarage of 12 months	Determined with regular radiological scans once every 9 weeks and measured following RECIST 1.1
To determine if there is an association between measured drug blood levels and treatment outcome measured as response to treatment determined by RECIST	During treatment, expected avarage of 12 months	Drug trough levels will be taken once every 3 weeks and stored frozen until measurement at the end of the study
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.	During treatment, expected avarage of 12 months	All patients who are willing to undergo extra tissue collection will have a tumor and where possible a polyp biopsy before treatment and for tumor biopsy in week 2 and 4 and for polyps once every 6 months during treatment for biomarker investigations. The activity of mTOR and its downstream targets will be measured in the tumor as well as the arborization pattern and apoptosis activity in the polyps.
To determine the safety and toxicity of Everolimus in this patient population	During treatment, expected avarage of 12 months	Number of Participants with Adverse Events determined by the CTCAE 4.0 as a Measure of Safety and Tolerability

Trial Locations

Locations (2)

Academic Medical Center; 🇳🇱 Amsterdam, Netherlands

Erasmus Medical Center; 🇳🇱 Rotterdam, Netherlands