Randomized phase II study of brostallicin (PNU-166196A) versus doxorubicin as first line chemotherapy in patients with advanced or metastatic soft tissue sarcoma

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 108

Inclusion Criteria

- Histologically proven advanced and/or metastatic malignant soft tissue sarcoma of high or intermediate grade, and of one of the following histologies (WHO classification 2002):
. Adipocytic (liposarcoma dedifferentiated, myxoid/round cell, pleomorphic, mixed-type, not otherwise specified)
. Fibroblastic (adult fibrosarcoma, myxofibrosarcoma, sclerosing epithelioid fibrosarcoma)
. So-called fibrohistiocytic (pleomorphic Malignant Fibrous Histiocytoma (MFH), giant cell MFH”, inflammatory MFH”)
. Leiomyosarcoma
. Malignant glomus tumors
. Skeletal muscles (rhabdomyosarcoma, alveolar or pleomorphic) excluding embryonal rhabdomyosarcoma
. Vascular (epithelioid haemangioendothelioma, angiosarcoma)
. Uncertain differentiation (synovial, epithelioid, alveolar soft part, clear cell, desmoplastic small round cell, extra-renal rhabdoid, malignant mesenchymoma, perivascular epithelioid cell tumor (PEComa), intimal sarcoma) excluding chondrosarcoma, Ewing tumors / Primitive neuroectodermal tumor (PNET)
. Malignant peripheral nerve sheath tumors
. Malignant solitary fibrous tumors
. Undifferentiated soft tissue sarcomas not otherwise specified
. Other types of sarcoma (not listed as ineligible), if approved by the Study Coordinator (written or e-mail approval needed prior to registration)

-Formalin fixed paraffin embedded tumour blocks and representative H/E (haematoxylin/eosin) slides must be available for histological central review. Histological central review is not required before treatment start but is mandatory within 14 days of registration. Local histopathological diagnosis will be accepted for entry into the study

-Relapsed, refractory and/or metastatic disease incurable by surgery or radiotherapy

- Presence of measurable disease (according to RECIST criteria)

- No prior chemotherapy regimen for advanced or metastatic disease; (neo)adjuvant therapy is allowed

- At least 60 years of age, or patients at least 18 years of age non suitable for intensive chemotherapy combination treatments

- WHO performance status 0 or 1

- Absence of symptomatic or known CNS metastases

- Adequate bone marrow function (ANC> 2 x 1000000000/l, PLA>100 x 1000000000/l)

- Adequate hepatic function (bilirubin = 1.5 UNL , SGOT/AST = 2.5 UNL and SGPT/ALT = 2.5 UNL, Alk.phos = 2.5 UNL)

- Adequate renal function: calculated or measured creatinine clearance = 60 ml/min (see Appendix C)

- Clinically normal cardiac function (LVEF assessed by MUGA or ECHO), normal 12 lead ECG, and in the past 6 months no serious cardiac illness or medical condition including but not confined to:
. History of documented congestive heart failure (CHF)
. High-risk uncontrolled arrhythmias
. Angina pectoris requiring antianginal medication
. Clinically significant valvular heart disease
. Evidence of transmural infarction on ECG
. Poorly controlled hypertension (e.g. systolic >180mm Hg or diastolic greater than 100mm Hg)

- No prior history of malignancies other than sarcoma (except for basal

Exclusion Criteria

The following tumor types are ineligible:
. Embryonal rhabdomyosarcoma
. Chondrosarcoma
. Osteosarcoma
. Ewing tumors / PNET
. Gastro-intestinal stromal tumors
. Dermatofibrosarcoma protuberans
. Inflammatory myofibroblastic sarcoma
. Neuroblastoma
. Malignant mesothelioma
. Mixed mesodermal tumors of the uterus.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the activity of Brostallicin measured as 6 months progression free survival when used as first line chemotherapy in patients with advanced or metastatic soft tissue sarcoma.;<br> Secondary Objective: To evaluate the activity of the compound on efficacy endpoints, such as objective response rate, duration of response, overall progression free survival and overall survival.<br><br> To evaluate the safety in the concerned population.<br> ;Primary end point(s): 6 months progression free survival: patients considered as CR, PR or NC according to RECIST at the 26 weeks evaluation will be considered as successes”.

Secondary Outcome Measures

Name	Time	Method

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