Metastatic Adult Soft Tissue Sarcoma
Conditions
Keywords
NGR-hTNF, Doxorubicin, Soft Tissue Sarcoma
Brief 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.
Detailed description
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).
Interventions
DRUGlow-dose NGR-hTNF
NGR-hTNF: 0.8 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
DRUGhigh-dose NGR-hTNF
NGR-hTNF: 45 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
DRUGDoxorubicin
Doxorubicin: 60 mg/m² intravenous infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles or until cumulative dose of 550 mg/m²
Sponsors
AGC Biologics S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | every 6-12 weeks | Defined as the time from the date of randomization until disease progression, or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Toxicity according to NCI-CTCAE criteria (version 4.02) | during the study | To evaluate safety and toxicity profile related to NGR-hTNF |
| Duration of Disease Control | every 6-12 weeks | Measured from the date of randomization until disease progression, or death due to any cause |
| Overall survival (OS) | every 6-12 weeks | Defined as the time from the date of randomization until the date of death due to any cause or the last date the patient was known to be alive |
| Response rate | every 6-12 weeks | Measured both according to RECIST criteria and by FDG-PET |
| Tumor response | every 6-12 weeks | Evaluated by a centralized review of changes in tumor density on CT scan and/or perfusion MRI |
Countries
France, Italy, United Kingdom
Outcome results
None listed