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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Erasmus Medical Center
Information provided by (Responsible Party):
Heinz-Josef Klumpen, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01178151
First received: July 26, 2010
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Peutz-Jeghers Syndrome
Neoplastic Processes
Neoplasm Metastasis
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Everolimus in the Treatment of Neoplasms in Patients With Peutz-Jeghers Syndrome

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • To determine the response rate of Everolimus in patients with advanced cancer and PJS. [ Time Frame: During treatment, expected avarage of 12 months ] [ Designated as safety issue: No ]
    Determined with regular radiological scans once every 9 weeks and measured following RECIST 1.1


Secondary Outcome Measures:
  • To determine the overall survival of PJS patients treated with everolimus for advanced malignancies [ Time Frame: avarage of 18 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 15
Study Start Date: October 2010
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: afinitor
10mg afinitor daily orally
Drug: Everolimus
10mg daily orally
Other Name: Afinitor, RAD001, everolimus

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01178151

Locations
Netherlands
Academic Medical Center
Amsterdam, Netherlands, 1105AZ
Erasmus Medical Center
Rotterdam, Netherlands, 3000 CA
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Erasmus Medical Center
Investigators
Principal Investigator: Heinz-Josef Klumpen, MD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  More Information

No publications provided

Responsible Party: Heinz-Josef Klumpen, MD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01178151     History of Changes
Other Study ID Numbers: AMCmedonc010, 2010-020451-32
Study First Received: July 26, 2010
Last Updated: July 1, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Peutz-Jeghers syndrome
mTOR inhibition
cancer

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Peutz-Jeghers Syndrome
Syndrome
Digestive System Diseases
Disease
Gastrointestinal Diseases
Genetic Diseases, Inborn
Hyperpigmentation
Intestinal Diseases
Intestinal Polyposis
Lentigo
Melanosis
Neoplastic Syndromes, Hereditary
Pathologic Processes
Pigmentation Disorders
Skin Diseases
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014