A Phase II, Multicenter Study to Explore the Efficacy and Safety of Brostallicin in Patients With Myxoid Liposarcoma With (12:16) Translocation
1. Patient has provided informed consent.
2. Histologically confirmed myxoid liposarcoma.
3. Patients with metastatic and/or unresectable myxoid liposarcoma that is progressive
and standard curative measures do not exist or are no longer effective.
4. Patient has measurable tumor on CT, spiral CT, or MRI scan that meet RECIST criteria.
5. Age ≥18 years
6. Karnofsky performance status (KPS) ≥ 70% (see Appendix III).
7. Life expectancy of at least 3 months.
8. Acceptable liver function:
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST (SGOT), ALT (SGPT) and alkaline phosphatase ≤ 2.5 times ULN (if liver
metastases are present, then ≤ 5 × ULN is allowed).
9. Acceptable renal function: For all patients serum creatinine within normal limits, OR
calculated creatinine clearance ≥ 60 mL/min/1.73 m(2) for patients with creatinine
levels above institutional normal.
10. Acceptable hematologic status:
- Absolute neutrophil count (ANC) ≥ 1500 cells/mm(3) (1.5 ×10(9)/L)
- Platelet count ≥ 100,000 platelet/mm(3) (100 ×10(9)/L)
- Hemoglobin ≥ 9 g/dL.
1. Patient received any of the following within the specified time period prior to
initiation of treatment in this study:
- Chemotherapy, major surgery, significant traumatic injury, or irradiation,
whether conventional or investigational within 28 days
- Mitomycin-C or nitrosurea within 42 days.
- ET-743 at any time (Stage 1 only).
2. Patients heavily pretreated with chemotherapy and radiation, defined as follows:
- ≥ 12 cycles of an alkylating agent-containing regimen, or
- > 2 cycles carboplatin, or
- > 2 cycles mitomycin C, or
- irradiation to 25% of bone marrow-containing areas, or
- high-dose chemotherapy requiring hematopoietic stem-cell reinfusion.
3. Known hypersensitivity to any study drug component.
4. Uncontrolled brain metastases in the judgement of the Investigator.
5. Abnormal cardiac or cardiovascular function, or serious cardiac illness or medical
condition in the previous 6 months including, but not confined to:
- New York Heart Association (NYHA) grade 2 or higher congestive heart failure
(CHF) or who has had angioplasty or placement of coronary stents within the
previous 6 months
- Myocardial infarction within the past 6 months
- High-risk uncontrolled arrhythmias
- Angina pectoris that requires antianginal medication
- Has clinically significant valvular heart disease
- Evidence of transmural infarction on ECG
- Poorly controlled hypertension (e.g., blood pressure: systolic >180 mm Hg or
diastolic >100 mm Hg).
6. Pregnant or lactating females. All patients (males and females) who are fertile must
agree to use an effective barrier method of birth control (i.e., latex condom,
diaphragm, cervical cap, etc) to avoid pregnancy.
7. Not recovered from acute toxicity of all previous therapy prior to enrollment.
8. History of prior malignancies within 3 years, except for basal cell or squamous cell
carcinoma of the skin, carcinoma in situ of the cervix or breast.
9. Any evidence of serious and/or unstable pre-existing medical, psychiatric, or other
condition (including laboratory abnormalities) that could interfere with patient
safety or obtaining informed consent.
10. Any active uncontrolled infection including AIDS, hepatitis B or C.
11. Any psychological, familial, sociological, or geographical condition that could
potentially interfere with compliance with the study protocol and follow up schedule.