Treatment of Metastatic Soft Tissue Sarcoma (STS) Patients (FIBROSARC USA)

Inclusion Criteria:

Patients may be included in the study only if they meet all of the following criteria:

1. Age 16 - 75 years. Patients under 18 years, should be fully grown (prove of fused
growth plates).

2. Patients with histological evidence of advanced unresectable and/or metastatic
high-gradesoft tissue sarcoma (grade 2 - 3 according to the FNLCC grading system) not
amenable to curative treatment with surgery or radiotherapy. The following tumor types
are included:

- Malignant fibrous histiocytoma (undifferentiated pleomorphic sarcoma)

- Myxoid and round cell liposarcoma, pleomorphic liposarcoma or dedifferentiated
liposarcoma

- Myxofibrosarcoma intermediate and high-grade

- Fibrosarcoma

- Leiomyosarcoma

- Angiosarcoma

- Unclassified sarcoma NOS

The following tumor types will not be included:

- GIST

- Mixed mesodermal tumor

- Synovial sarcoma

- Malignant peripheral nerve sheath tumor

- Epithelioid sarcoma

- Embryonal rhabdomyosarcoma

- Chondrosarcoma

- Malignant mesothelioma

- Neuroblastoma

- Osteosarcoma

- Ewing's sarcoma / primitive neuroectodermal tumor

- Desmoplastic small round cell tumor

- Alveolar soft part sarcoma

- Pleomorphic rhabdomyosarcoma

- Alveolar rhabdomyosarcoma

3. Patients must have at least one unidimensionally measurable lesion by computed
tomography as defined by RECIST criteria 1.1. If only 1 lesion is present at
screening, this lesion should not have been irradiated during previous treatments.

4. Life expectancy of at least 3 months in the judgment of the investigator.

5. ECOG ≤ 2.

6. Documented negative test for HIV-HBV-HCV. For HBV serology: the determination of
HBsAg, anti-HBsAg-Ab and anti-HBcAg-Ab is required. In patients with serology
documenting previous exposure to HBV (i.e., anti-HBs Ab with no history of vaccination
and/or anti-HBc Ab), negative serum HBV-DNA is required. For HCV: HCV-RNA or HCV
antibody test. Subjects with a positive test for HCV antibody but no detection of
HCV-RNA indicating no current infection are eligible.

7. Female patients: negative serum pregnancy test for women of childbearing potential
(WOCBP)* within 14 days of starting treatment. WOCBP must agree to use, from the
screening to six months following the last study drug administration, highly effective
contraception methods, as defined by the "Recommendations for contraception and
pregnancy testing in clinical trials" issued by the Head of Medicine Agencies'
ClinicalTrial Facilitation Group (www.hma.eu/ctfg.html) and which include, for
instance, progesterone-only or combined (estrogen- and progesterone-containing)
hormonal contraception associated with inhibition of ovulation, intrauterine devices,
intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomized
partner or sexual abstinence.

Male patients: Male subjects able to father children must agree to use two acceptable
methods of contraception throughout the study (e.g. condom with spermicidal gel).
Double-barrier contraception is required.

* Women of childbearing potential are defined as females who have experienced
menarche, are not postmenopausal (12 months with no menses without an alternative
medical cause) and are not permanently sterilized (e.g., tubal occlusion,
hysterectomy, bilateral oophorectomy or bilateral salpingectomy).

8. Informed consent signed and dated to participate in the study.

9. Willingness and ability to comply with the scheduled visits, treatment plan,
laboratory tests and other study procedures.

Exclusion Criteria:

Patients will be excluded from participating in this study if they meet 1 or more of the
following criteria:

1. Prior therapy (except surgery and radiation) for unresectable or metastatic malignant
soft tissue sarcoma.

2. Previous treatment with anthracycline-containing chemotherapy.

3. Radiotherapy within 4 weeks prior to therapy.

4. Known history of allergy to TNFα, anthracyclines or other intravenously administered
human proteins/peptides/antibodies.

5. Absolute neutrophil count (ANC) < 1.5 x 109/L, platelets < 100 x 109/L and haemoglobin
(Hb) < 9.0 g/dl.

6. Chronically impaired renal function as expressed by creatinine clearance < 60 mL/min.

7. Inadequate liver function (ALT, AST, ALP or total bilirubin ≥ 2.5 x ULN)

8. Any severe concomitant condition which makes it undesirable for the patient to
participate in the study or which could jeopardize compliance with the protocol.

9. History within the last year of cerebrovascular disease and/or acute or subacute
coronary syndromes including myocardial infarction, unstable or severe stable angina
pectoris.

10. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).

11. Clinically significant cardiac arrhythmias or requiring permanent medication.

12. Abnormalities observed during baseline ECG and Echocardiogram investigations that are
considered as clinically significant by the investigator. Subjects with current, or a
history of QT/QTc prolongation would be excluded. In particular:

- patients with a marked prolongation of QT/QTc interval (e.g., repeated
demonstration of QTc >480 milliseconds using Fredricia's QT correction formula)
are excluded;

- patients with a history of risk factors for Torsades de Pointes (e.g., heart
failure, hypokalemia, family history of prolonged QT syndrome) are excluded;

- patients who require the use of concomitant medications that prolong the QT/QTc
interval are excluded.

13. Uncontrolled hypertension, despite optimal therapy.

14. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine
classification).

15. Severe diabetic retinopathy such as severe non-proliferative retinopathy and
proliferative retinopathy.

16. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery)
within 4 weeks of administration of study treatment.

17. Pregnancy or breast-feeding.

18. Requirement of chronic administration of corticosteroids or other immunosuppressant
drugs. Limited use of corticosteroids to treat or prevent acute hypersensitivity
reactions is not considered an exclusion criterion.

19. Presence of active and uncontrolled infections or other severe concurrent disease
which, in the opinion of the investigator, would place the patient at undue risk or
interfere with the study.

20. Known active or latent tuberculosis (TB).

21. Concurrent malignancies other than Soft Tissue Sarcoma, unless the patient has been
disease-free for at least 2 years.

22. Growth factors or immunomodulatory agents within 7 days prior to the administration of
study treatment.

23. Serious, non-healing wound, ulcer or bone fracture.

24. Allergy to study medication or excipients in study medication.

25. Concurrent therapy with anticoagulants.

26. Concurrent use of other anti-cancer treatments or agents other than study medication.

27. Any recent live vaccination within 4 weeks prior to treatment or plan to receive
vaccination during the study.