E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Malignant Pleural Mesothelioma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059518 |
E.1.2 | Term | Pleural mesothelioma malignant |
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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 |
To assess the antitumor activity in terms of TTP of PHA-848125AC as second-line treatment in pemetrexed-pretreated patients with MPM. |
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E.2.2 | Secondary objectives of the trial |
- to assess additional measures of tumor control to further characterize the efficacy profile of PHA-848125AC in MPM patients - to evaluate the safety profile of repeated administrations of PHA-848125AC in MPM patients - to monitor blood levels of PHA-848125AC through a limited PK sampling procedure. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated IRB/IEC-approved Informed Consent 2. Histologically or cytologically proven diagnosis of Malignant Pleural Mesothelioma (MPM), inoperable, in relapse after failure of prior pemetrexed-containing treatment (only one prior chemotherapy regimen allowed) 3. Presence of unidimensionally and/or bidimensionally measurable disease. Patients undergoing palliative radiation therapy for painful lesions are allowed to enter the study, provided that they have measurable disease outside the irradiated site. 4. No or asymptomatic pleural effusion. Patients with symptomatic pleural effusions can be enrolled provided that they have their effusions drained prior to enrollment on the clinical trial. 5. Age >/= 18 years 6. ECOG performance status 0-1 7. Estimated life expectancy of at least 3 months 8. Negative pregnancy test (if female in reproductive years) 9. Agreement upon the use of effective contraceptive methods (hormonal or barrier method of birth control, or abstinence) prior to study entry and for the duration of study participation, if men and women of child producing potential 10. Adequate liver function: - Bilirubin </= upper limit of normal (ULN) - Albumin >/= 3.0 g/dL - AST (SGOT), ALT (SGPT) </= 2.5 ULN (if liver metastases are present, then </= 5 ULN is allowed) - Alkaline phosphatase </= 2.5 ULN (if liver and/or bone metastases are present, then </= 5 ULN is allowed) 11. Adequate renal function: - serum creatinine </= ULN 12. Adequate hematologic status: - ANC >/= 1,500 cells/mm3 - Platelet count >/= 100,000 cells/mm3 - Hemoglobin >/= 9.0 g/dL 13. At the time of start of treatment, at least 4 weeks must have elapsed since completion of prior chemotherapy, surgery, radiotherapy (provided that no more than 25% of bone marrow reserve has been irradiated) 14. With the exception of alopecia, resolution of all acute toxic effects of any prior chemotherapy, surgery or radiotherapy to NCI CTC (Version 3.0) grade </= 1 and to the baseline laboratory values as defined in Inclusion Criteria Number 10, 11, 12 15. Able and willing to comply with scheduled visits, therapy plans, and laboratory tests required in this protocol 16. Capability to swallow capsules intact (without chewing, crushing, or opening). |
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E.4 | Principal exclusion criteria |
1. Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis 2. Grade >1 retinopathy 3. Known brain metastases 4. Major surgery, other than diagnostic surgery, within 4 weeks prior to treatment 5. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy 6. Known infection with HIV, active hepatitis B or hepatitis C 7. Pregnant or breast feeding women 8. Previous (within the last 5 years) or current malignancies at other sites, except for adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri 9. Current enrollment in or participation in another therapeutic clinical trial within 4 weeks preceeding treatment start 10. Diabetes mellitus uncontrolled 11. Gastrointestinal disease (e.g. Crohns disease, ulcerative colitis, or short gut syndrome) that would impact on drug absorption 12. Patients under treatment with anticoagulants or with coagulation disorders or with signs of hemorrhage at baseline 13. Patients with previous history or current presence of neurological disorders, including epilepsy (although controlled by anticonvulsant therapy), Parkinsons disease and extra-pyramidal syndromes 14. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgement of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be based on the Time to Tumor Progression (TTP), i.e. the time from the date of treatment start to the date of first documentation of objective tumor progression, objective tumor recurrence or of death due to progressive disease (PD), whichever comes first. The primary efficacy analysis will be performed on the proportion of evaluable patients in a progression free-status at 12 weeks: 12-week PD-free rate. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | No |
E.8.1.2 | Open | No |
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) | 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 | 7 |
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 | 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
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La sperimentazione si definisce conclusa quando il numero completo di pazienti specificato dal protocollo risulta pienamente valutabile per l`endpoint primario (assenza di progressione a 12 settimane) |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |