phase ii study of ngr-htnf in combination with doxorubicin in patients affected by soft tissue sarcomas.

Conditions: Metastatic Adult Soft Tissue Sarcoma

Summary: the main objective of the trial is to document the preliminary antitumor activity of two doses of ngr-htnf administered either alone or in combination with doxorubicin in locally advanced or metastatic soft-tissue sarcoma (sts) patients untreated or previously treated with one or more prior systemic regimen.

considering the safety/toxicity profile of ngr-htnf characterized by mild-to-moderate constitutional symptoms when given either every three weeks or weekly both at low (0.8 µg/m\^2) and high dose (45 µg/m\^2); the reversibility of these adverse events generally occurring only during the infusion time; the absence of overlapping toxicities with chemotherapeutic agents; and the safety and preliminary antitumor activity observed in phase ib trial with doxorubicin, seems justified to evaluate in a randomized 4-arm phase ii trial the preliminary antitumor activity of two doses of ngr-htnf (0.8 µg/m\^2 and 45 µg/m\^2) administered weekly either alone or in combination with a standard dose of doxorubicin (60 mg/m\^2 every three weeks).

Eligibility criteria:
inclusion criteria: * patients ≥ 18 years * histologically-proven, locally advanced, or metastatic sts (excluding extraosseus ewing sarcoma) * patients not amenable to surgery, radiotherapy, or combined-modality therapy with curative intent * patients untreated or previously treated with one or more systemic regimen * ecog performance status 0-2 (appendix a) * at least one untreated (not previously irradiated) target lesion that could be measured in one dimension, according to recist criteria * a life expectancy of 12 weeks or more * adequate baseline bone marrow, hepatic and renal function, defined as follows: * neutrophils \> 1.5 x 109/l and platelets \> 100 x 109/l * bilirubin \< 1.5 x uln * ast and/or alt \< 2.5 x uln in absence of liver metastasis or \< 5 x uln in presence of liver metastasis * serum creatinine \< 1.5 x uln * creatinine clearance (estimated according to cockcroft-gault formula) ≥ 50 ml/min * patients may have had prior treatment providing the following conditions are met before treatment start: * surgery and radiation therapy: wash-out period of 14 days * systemic therapy: wash-out period of 21 days * patients must give written informed consent exclusion criteria: * patients may not receive any other investigational agents while on study * patients with myocardial infarction within the last six (6) months, unstable angina, new york heart association (nyha) grade ii or greater congestive heart failure, or serious cardiac arrhythmia requiring medication * lvef \< 55% (only for patients candidate for doxorubicin treatment) * uncontrolled hypertension * prolonged qtc interval (congenital or acquired) \> 450 ms * history or evidence upon physical examination of cns disease unless adequately treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard medical therapy) or history of stroke * patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol * known hypersensitivity/allergic reaction or contraindications to human albumin preparations or to any of the excipients * any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol * pregnancy or lactation. patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. women of child-bearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration

Keywords: ngr-htnf doxorubicin soft tissue sarcoma