A Phase II Study of Amrubicin in Relapsed or Refractory Thymic Malignancies

• Overall response rate (ORR) = (CR+PR) in patients with thymic malignancies. ORR assessed radiographically by RECIST criteria. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• progression-free survival in patients with thymic malignancies treated with amrubicin [ Time Frame: 2 years ] [ Designated as safety issue: No ]

• Evaluate the Overall response rate (ORR) = (CR+PR) in patients with thymic malignancies. ORR will be assessed radiographically by RECIST criteria. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Evaluate progression-free survival in patients with thymic malignancies treated with amrubicin [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Primary Objectives: Assessment of efficacy

Secondary Objectives: Assessment of toxicity

• Thymoma
• Thymus Cancer
• Thymic Carcinoma

Inclusion Criteria:

3.1.1. Histologically or cytologically confirmed invasive or metastatic thymoma or thymic carcinoma. Locally invasive disease is acceptable, provided it is not resectable.

3.1.2. Previous treatment with at least one prior chemotherapy regimen. There is no limit on number of prior chemotherapy regimens.

3.1.3. Documented progressive disease after the most recent chemotherapy regimen.

3.1.4. Presence of measurable disease on imaging within 4 weeks prior to first dose, as defined per RECIST 1.1. See Section 9 regarding evaluation of measurable disease.

3.1.5. Completion of prior systemic therapy at least 4 weeks prior to first dose.

3.1.6. Prior treatment with immunotherapy is allowed, provided such therapy was completed at least 8 weeks prior to first dose.

3.1.7. Prior treatment with surgery is allowed, provided the surgery was completed at least 4 weeks prior to first dose and the patient is adequately recovered from surgery.

3.1.8. Prior radiation therapy is allowed, provided there are no residual toxic effects of therapy. Chest radiotherapy with curative intent to the primary disease complex must have been completed >= 28 days prior to first dose. Cranial radiation must have been completed >= 21 days prior to first dose. Radiotherapy to all other areas must have been completed >= 7 days prior to first dose.

3.1.9. Age >= 18 years.

3.1.10. ECOG performance status of 0 or 1.

3.1.11. Adequate hematologic function as determined by the following tests within 4 weeks prior to first dose: 3.1.11.1. leukocytes >= 3000/mm3 3.1.11.2. absolute neutrophil count >= 1500/mm3 3.1.11.3. platelets >= 100,000/mm3 3.1.11.4. hemoglobin >= 9 g/d

3.1.12. Adequate hepatic function as determined by the following tests within 4 weeks prior to first dose: 3.1.12.1. serum bilirubin <1.5 x institutional upper limit of normal (ULN) 3.1.12.2. AST and ALT <3 x ULN

3.1.13. Adequate renal function as determined by the following tests within 4 weeks prior to first dose: 3.1.13.1. serum creatinine <1.5 times institutional upper limit of normal 3.1.13.2. if serum creatinine above institutional upper limit of normal, calculated serum creatinine clearance by the Cockcroft Gault method > 60 mL/min

3.1.14. Adequate cardiac function as determined by the following tests within 4 weeks prior to first dose: 3.1.14.1. left ventricular ejection fraction (LVEF) >= 50% by transthoracic echocardiogram (TTE) or multiple gated acquisition scan (MUGA)

3.1.15. For females of childbearing potential, negative serum pregnancy test within 4 weeks of first dose.

3.1.16. For males and females of childbearing potential, use of effective contraceptive methods during the study.

3.1.17. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

3.2.1. Current use, or use within 4 weeks prior to first dose, of any other investigational agents.

3.2.2. Known history of allergic reactions attributed to compounds of similar chemical or biologic composition to amrubicin.

3.2.3. Active malignancy requiring treatment other than thymic malignancy.

3.2.4. Pregnant or nursing females due to unknown toxic effects of amrubicin on the developing fetus or in breast milk. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

3.2.5. Symptomatic central nervous system metastatic disease. Patients with asymptomatic brain metastases allowed. If treated with surgical resection or radiation therapy, the patient must be stable for >= 2 weeks after completion of therapy. If the patient is on corticosteroids, the dose of corticosteroids, the dose of corticosteroids must have been stable for >= 2 weeks prior to first dose of study treatment, or be in the process of being tapered.

3.2.6. Concurrent severe or uncontrolled medical disease (including but not limited to active systemic infection, diabetes, hypertension, coronary artery disease, congestive hear failure and mental illness) that in the opinion of the investigator would compromise the safety of the patient or compromise the ability of the patient to complete the study.

3.2.7. Known history of seropositive human immunodeficiency virus (HIV) or use of immunosuppressive medications for other conditions that would, in the opinion of the investigator, increase the risk of serious neutropenic complications.