Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma

Phase II Study Of Oral PHA-848125AC In Patients With Thymic Carcinoma Previously Treated With Chemotherapy

The intent of the study is to assess the antitumor activity of PHA-848125AC as second-line treatment in patients with recurrent or metastatic, unresectable thymic carcinoma previously treated with chemotherapy.

The Simon's optimal 2 stage design is adopted for this single-arm, open-label, multicenter phase II clinical trial of PHA-848125AC administered to patients with recurrent or metastatic, unresectable thymic carcinoma previously treated with chemotherapy (only one prior systemic therapy allowed). The intent of the study is to assess the antitumor activity of PHA-848125AC and ultimately to improve the outcome of patients with thymic carcinoma who have already exploited one chemotherapy option. The primary end point for this study is a progression free survival rate of 3 months.

Inclusion Criteria:

• Histologically or cytologically proven diagnosis of unresectable B3 thymoma or thymic carcinoma recurrent or progressing after prior chemotherapy (only one prior systemic therapy allowed)
• Presence of measurable disease
• Age >=18 years
• ECOG performance status 0-1
• Negative pregnancy test (if female in reproductive years)
• Use of effective contraceptive methods if men and women of child producing potential
• Adequate liver function Total Serum Bilirubin <=1.5 x upper limit of normal (ULN) Transaminases (AST/ALT) <=2.5ULN (if liver metastases are present, then <=5ULN is allowed) ALP <=2.5ULN (if liver and/or bone metastases are present, then <=5ULN is allowed)
• Adequate renal function Serum Creatinine <=ULN or Creatinine Clearance calculated by Cockcroft and Gault's formula > 60 mL/min.
• Adequate hematologic status ANC >=1,500cells/mm3 Platelet Count >=100,000cells/mm3 Hemoglobin >=9.0g/dL
• Two 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)
• Resolution of all acute toxic effects of any prior treatments to NCI CTC (Version 3.0) grade <=1

Exclusion Criteria:

• 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
• Grade >1 retinopathy
• Known brain metastases
• Known active infections
• Pregnant or breast feeding women
• Diabetes mellitus uncontrolled
• Gastrointestinal disease that would impact on drug absorption
• Patients under treatment with anticoagulants or with coagulation disorders or with signs of hemorrhage at baseline
• Patients with previous history or current presence of neurological disorders, including epilepsy (although controlled by anticonvulsant therapy), Parkinson's disease and extra-pyramidal syndromes
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that make the patient inappropriate for entry into this study