Study Of Oral PHA-848125AC In Patients With Malignant Thymoma Previously Treated With Multiple Lines Of Chemotherapy

This is a single-arm, open-label, multicenter, phase II clinical trial design with an early
stopping rules. PHA-848125AC will be administered to patients with recurrent metastatic
unresectable B3 thymoma or thymic carcinoma who have received more than one line of prior
systemic therapy for advanced / metastatic disease. The intent of the study is to assess the
antitumor activity of PHA-848125AC and ultimately to improve the outcome of the patients. The
primary end point for this study is a progression free survival rate of 3 months.

Inclusion Criteria:

- Signed and dated IRB/Approved Informed Consent

- Histologically or cytologically proven diagnosis of unresectable B3 thymoma or thymic
carcinoma recurrent or progressing after more than one prior systemic therapy for
advanced / metastatic disease

- Presence of measurable disease

- Age >=18 years old

- 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 (with the
exception of myasthenia gravis), 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