E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic non small lungcancer |
|
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary purpose of the phase I part of the trial is to establish the tolerance dose (maximum tolerated dose (MTD) and dose limiting toxicity (DLT). The phase II part of the study is to assess the efficacy of Belinostat and Erlotinib in combination assessed by disease control rate, defined as non - progression at 3 months / Stable disease or better) using RECIST response criteria version 1.1.
|
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the Phase II part of the trial are • Time to progression • Overall survival • Identification of possible predictive factors
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed consent of an approved informed consent form 2. A. For the dose escalation phase: Patients with histological or cytological confirmed non-small cell lung cancer who are rated suitable for treatment with Erlotinib B. For MTD expansion phase: Patients diagnosed with non- small cell lung cancer rated suitable for treatment with Erlotinib and with measurable disease according to RECIST version 1.1 3. Performance status (ECOG) ≤ 2 4. Life expectancy at least 3 months 5. Age ≥ 18 years 6. Acceptable liver, kidney and bone marrow function, defined as: a. Bilirubin ≤ 1.5 x upper limit of normal (ULN) b. ASAT, ALAT and alkaline phosphatase ≤ 3 x ULN (if liver metastases is ≤ 5 x ULN allowed) c. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) d. WBC> 2.5 x 109 / l, neutrophils> 1.0 x 109 / l, platelets> 100 x 109 / l e. Hemoglobin> 9.0 g / dl or> 5.6 mmol / l 7. Acceptable coagulation: PT and APTT within ≤ 1.5 x ULN or in the therapeutic range if given anticoagulant 8. A negative pregnancy test for women of childbearing age. In fertile men and women the use of effective contraception methods are required during the trial 9. Serum potassium within normal range
|
|
E.4 | Principal exclusion criteria |
1. Treatment with experimental drugs within the last 4 weeks 2. Former anti-cancer therapy within the last 3 weeks before the start of experimental treatment, including chemotherapy, radiotherapy, endocrine therapy or immunotherapy. 3. Simultaneous presence of active infection or other concomitant present medical condition likely to affect the experimental procedures, including significant cardiovascular disease (New York Heart Association Class III or IV heart disease, myocardial infarction within the past 6 months, unstable angina, congestive heart failure requiring treatment, unstable arrhythmia or the need for antiarrhythmic drugs or signs of ischemia on ECG, marked baseline prolongation of QT / QTc interval, for example repeated demonstration of a QTc interval> 500 msec; long QT syndrome; required the use of concurrent medication on dosage belinostat days, which may cause torsades de pointes (see Appendix 1). 4. Altered mental status that prevents understanding of the informed consent process and / or execution of the necessary experiments 5. Secondary malignancy present (previous malignancy accepted if cured by treatment for > 3 years ago) 6. Intestinal obstruction or threatening bowel obstruction
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The proposed Belinostat-Erlotinib trial is designed as an open, non randomized phase I / II trial to assess the efficacy and safety of Belinostat in combination with Erlotinib in patients with non-small cell lung cancer who are eligible for treatment with erlotinib.
Purpose of the experiment The primary purpose of the phase I part of the trial is to establish the tolerance dose (maximum tolerated dose (MTD) and dose limiting toxicity (DLT). The phase II part of the study is to assess the efficacy of Belinostat and Erlotinib in combination assessed by disease control rate, defined as non - progression at 3 months / Stable disease or better) using RECIST response criteria version 1.1.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
maximum tolerated dose (MTD) dose limiting toxicity (DLT) |
|
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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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 | No |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 10 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 11 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 1 |