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

Brief Summary

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

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.

  • Study Type: Interventional
  • Study Design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
  • Study Primary Completion Date: September 2014

Interventions Used in this Clinical Trial

  • Drug: Everolimus
    • 10mg daily orally

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: afinitor
    • 10mg afinitor daily orally

Outcome Measures for this Clinical Trial

Primary Measures

  • To determine the response rate of Everolimus in patients with advanced cancer and PJS.
    • Time Frame: During treatment, expected avarage of 12 months
      Safety Issue?: No

Secondary Measures

  • To determine the overall survival of PJS patients treated with everolimus for advanced malignancies
    • Time Frame: avarage of 18 months
      Safety Issue?: No
  • To determine the time to progression of PJS patients treated with everolimus for advanced malignancies.
    • Time Frame: During treatment, expected avarage of 12 months
      Safety Issue?: No
  • To determine the safety and toxicity of Everolimus in this patient population
    • Time Frame: During treatment, expected avarage of 12 months
      Safety Issue?: Yes
  • 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
      Safety Issue?: No
  • 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
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

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 ╬╝mol/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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • Academisch Medisch Centrum – Universiteit van Amsterdam (AMC-UvA)
  • Collaborator
    • Erasmus Medical Center
  • Provider of Information About this Clinical Study
    • Principal Investigator: Heinz-Josef Klumpen, MD – Academisch Medisch Centrum – Universiteit van Amsterdam (AMC-UvA)
  • Overall Official(s)
    • Heinz-Josef Klumpen, MD, Principal Investigator, Academisch Medisch Centrum – Universiteit van Amsterdam (AMC-UvA)

Source

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The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT01178151