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

Neoplasm Metastasis Clinical Trial

— EVAMP  

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01178151
• Other study ID #: AMCmedonc010
• Secondary ID: 2010-020451-32
• Status: Withdrawn
• Phase: Phase 2
• First received: July 26, 2010
• Last updated: April 21, 2015
• Start date: October 2010
• Est. completion date: April 2015

Study information

• Verified date: April 2015
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasm Metastasis
• Neoplastic Processes
• Peutz-Jeghers Syndrome
• Syndrome

Intervention

Drug:
• Everolimus
10mg daily orally

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam
Netherlands	Erasmus Medical Center	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	During treatment, expected avarage of 12 months	No
Secondary	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.	avarage of 18 months	No
Secondary	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	During treatment, expected avarage of 12 months	No
Secondary	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	During treatment, expected avarage of 12 months	Yes
Secondary	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	During treatment, expected avarage of 12 months	No
Secondary	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.	During treatment, expected avarage of 12 months	No