E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced malignancy of any tumor type, not suitable for surgery at the time of study enter in patients with known Peutz-Jeghers disease (with LKB1 mutation). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034764 |
E.1.2 | Term | Peutz-Jeghers syndrome |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10029111 |
E.1.2 | Term | Neoplasms unspecified malignancy and site unspecified NEC |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10034764 |
E.1.2 | Term | Peutz-Jeghers syndrome |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the efficacy(as measured by objective tumor response) of single agent everolimus in the treatment of advanced malignancies of patients known with PJS |
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E.2.2 | Secondary objectives of the trial |
•To determine the overall survival of patients treated with everolimus in patients with advanced malignancies in PJS. •To evaluate the time to progression •To evaluate the toxicity profile of everolimus in PJS patients •To determine the association between drug levels of everolimus and objective clinical response •To determine the influence of everolimus on the proliferation signaling mTOR pathway and its downstream targets in the tumor and blood prior and during treatment with the use of established biomarkers.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Known Peutz-Jeghers disease (with LKB1 mutation) •Advanced malignancy of any tumor type, not suitable for surgery at the time of study enter •No concurrent systemic anti cancer treatment •No prior treatment with m-TOR inhibitor •Patients with prior malignancies or concurrent second malignancies are eligible •Prior systemic therapy is permitted with a washout time of at least 4 weeks •Cytological or histological confirmed carcinoma •Metastatic or non-resectable disease •Patients with clinically and/or radiographically documented measurable lesion according to RECIST criteria: X-ray, physical exam > 20 mm Spiral CT scan > 10 mm Non-spiral CT scan > 20 mm •ECOG/ WHO performance 0-2 •Age > 18 years •Life expectancy > 3 months •Adequate renal function (creatinine < 150 µmol/L) •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 •Adequate bone marrow function (WBC > 3.0 x 10 9/L, platelets > 100 x 10 9/L)
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E.4 | Principal exclusion criteria |
•Presence 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 •Patients who are pregnant or lactating •Patients who are of childbearing potential who do not agree to use a reliable contraceptive method throughout the study •Patients who do have serious concomitant systemic disorder that would compromise the safety of the patient, at the discretion of the investigator •Patients who are not willing to sign the Signed informed consent according to ICH/GCP, IRB approval obtained prior to treatment •Patients who do have uncontrolled symptomatic hyperglycaemia
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: Response rates Secondary endpoints: •Overall survival •Time to progression •Toxicity profile •Pharmacokinetic (measurement of drug trough levels) •Pharmacodynamics (measurement of pathway specific biomarkers)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |