E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent or metastatic unresectable thymic carcinoma |
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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 | 10055108 |
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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 | 10043674 |
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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 |
Assessment of the antitumor activity of PHA-848125AC as second-line treatment in patients with recurrent or metastatic, unresectable thymic carcinoma previously treated with chemotherapy. Antitumor activity will be evaluated on the basis of the progression-free survival status at 3 months. |
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E.2.2 | Secondary objectives of the trial |
Assessment of additional measures of tumor control to further characterize the efficacy profile of PHA-848125AC in recurrent or metastatic, unresectable thymic carcinoma previously treated with chemotherapy. Evaluation of the safety profile of repeated administrations of PHA-848125AC in patients with recurrent or metastatic, unresectable thymic carcinoma previously treated with chemotherapy. Exploratory Objective: Relationship between selected biomarkers baseline expression in tumor biopsies and treatment efficacy. |
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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 unresectable thymic carcinoma recurrent or progressing after prior chemotherapy (only one prior systemic therapy allowed). 3. Presence of measurable disease 4. Age >/= 18 years. 5. ECOG performance status 0-1. 6. Estimated life expectancy of at least 3 months. 7. Negative pregnancy test (if female in reproductive years). 8. 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. 9. Adequate liver function: Total Serum Bilirubin </= 1.5 x upper limit of normal (ULN) Transaminases (AST/ALT) </= 2.5 ULN (if liver metastases are present, then </= 5 ULN is allowed) ALP </= 2.5 ULN (if liver and/or bone metastases are present,then </= 5 ULN is allowed). 10. Adequate renal function: Serum Creatinine </= ULN. 11.Adequate hematologic status: ANC >/= 1,500 cells/mm3 Platelet Count >/= 100,000 cells/mm3 Hemoglobin >/= 9.0 g/dL. 12. At the time of start of treatment, at least 2 weeks must have elapsed since completion of prior chemotherapy, minor surgery, radiotherapy (provided that no more than 25% of bone marrow reserve has been irradiated). 13. 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 9, 10, 11. 14. Able and willing to comply with scheduled visits, therapy plans, and laboratory tests required in this protocol. 15. 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, uncontrolled cardiac arrhythmia, 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 as determined by an ophthalmologist. 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. 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 preceding treatment start. 10. Diabetes mellitus uncontrolled. 11. Gastrointestinal disease (e.g. Crohn s 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), Parkinson s 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 judgment 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) |
Progression-free survival rate at 3 months (PFS-3 rate). The PFS-3 rate, will be calculated as the proportion of evaluable patients known to be alive and progression-free at >/= 3 months since study treatment start out of the total number of evaluable patients. |
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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 | No |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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 conclusione della sperimentazione e` definita come la data dell` ultima visita dell` ultimo paziente, incluso il follow up. |
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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 | 1 |
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 | 1 |