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

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: Pilot Study of Everolimus in the Treatment of Neoplasms in Patients With Peutz-Jeghers Syndrome

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 Summary:
Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Current Primary Outcome: To determine the response rate of Everolimus in patients with advanced cancer and PJS. [ Time Frame: During treatment, expected avarage of 12 months ]

Determined with regular radiological scans once every 9 weeks and measured following RECIST 1.1


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • To determine the overall survival of PJS patients treated with everolimus for advanced malignancies [ Time Frame: 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. [ Time Frame: During treatment, expected avarage of 12 months ]
    Determined with regular radiological scans once every 9 weeks and measured following RECIST 1.1
  • To determine the safety and toxicity of Everolimus in this patient population [ Time Frame: 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
  • To determine if there is an association between measured drug blood levels and treatment outcome measured as response to treatment determined by RECIST [ Time Frame: 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. [ Time Frame: 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.


Original Secondary Outcome:

  • To determine the overall survival of PJS patients treated with everolimus for advanced malignancies [ Time Frame: Conclusion of the study, expected 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. [ Time Frame: During treatment, expected avarage of 12 months ]
    Determined with regular radiological scans once every 9 weeks and measured following RECIST 1.1
  • To determine the safety and toxicity of Everolimus in this patient population [ Time Frame: 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
  • To determine if there is an association between measured drug blood levels and treatment outcome measured as response to treatment determined by RECIST [ Time Frame: 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. [ Time Frame: 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.


Information By: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Dates:
Date Received: July 26, 2010
Date Started: October 2010
Date Completion:
Last Updated: April 21, 2015
Last Verified: April 2015