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Peutz-Jeghers SyndromePhase 2EVAMPNCT01178151

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

A Phase 2 study testing Everolimus in people with Peutz-Jeghers Syndrome and Neoplastic Processes, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 2 sites in Netherlands.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesNetherlands
Study dates
Oct 2010to Apr 2015
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Trial locations and contacts

2 sites in 1 country.

Netherlands2 sites

  • Academic Medical Center

    Amsterdam, 1105AZ

  • Erasmus Medical Center

    Rotterdam, 3000 CA

Other trials in Netherlands

About this study

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.

Being tested
Everolimus
Keywords
Peutz-Jeghers syndrome, mTOR inhibition, cancer
Medical subject headings
Peutz-Jeghers Syndrome, Neoplastic Processes, Neoplasm Metastasis, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called Afinitor, RAD001, everolimus

    10mg daily orally

Study groups in NCT01178151
Study groupRoleWhat they receive
afinitorExperimental10mg afinitor daily orally
Receives: Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To determine the response rate of Everolimus in patients with advanced cancer and PJS.

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

    Measured: During treatment, expected avarage of 12 months

Secondary outcomes (5)

  1. To determine the overall survival of PJS patients treated with everolimus for advanced malignancies

    The time between date of entering the study and date of death will be collected.

    Measured: avarage of 18 months

  2. To determine the time to progression of PJS patients treated with everolimus for advanced malignancies.

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

    Measured: During treatment, expected avarage of 12 months

  3. To determine the safety and toxicity of Everolimus in this patient population

    Number of Participants with Adverse Events determined by the CTCAE 4.0 as a Measure of Safety and Tolerability

    Measured: During treatment, expected avarage of 12 months

  4. To determine if there is an association between measured drug blood levels and treatment outcome measured as response to treatment determined by RECIST

    Drug trough levels will be taken once every 3 weeks and stored frozen until measurement at the end of the study

    Measured: During treatment, expected avarage of 12 months

  5. 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.

    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.

    Measured: During treatment, expected avarage of 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionApr 2015
  4. Study completionApr 2015

Why it stopped: No patients

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01178151
Sponsor's protocol ID
AMCmedonc010
Other IDs
2010-020451-32
Acronym
EVAMP
Status last verified
Apr 2015
First submitted
26 Jul 2010
Last updated
22 Apr 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • de Brabander J, Eskens FALM, Korsse SE, Dekker E, Dewint P, van Leerdam ME, van Eeden S, Klumpen HJ. Chemoprevention in Patients with Peutz-Jeghers Syndrome: Lessons Learned. Oncologist. 2018 Apr;23(4):399-e33. doi: 10.1634/theoncologist.2017-0682. Epub 2018 Jan 25.

    PubMed 29371475

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Everolimus in people with Peutz-Jeghers Syndrome and Neoplastic Processes, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 2 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 22 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To determine the response rate of Everolimus in patients with advanced cancer and PJS. (time frame: During treatment, expected avarage of 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01178151, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2015.

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