Assess the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of recombinant human tumor necrosis factor-α (rhTNF-α) when given as a single dose intravenously and in combination with liposomal doxorubicin in human subjects
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Infusion will be done over 60 minutes, preferably via central venous catheter. Will immediately follow the infusion of Liposomal doxorubicin.
Infusion over 60 minutes
Administration of Caelyx® will be done first, as infusion in 250 ml D5W, followed immediately by infusion of rhTNF-α.
Krankenhaus Nordwest
Frankfurt, Germany
Maximum Tolerated Dose (MTD) of a single dose of intravenous recombinant human tumor necrosis factor-α plus liposomal doxorubicin
MTD is the dose level below the one that produces 2 or more Dose-Limiting Toxicities
Time frame: Up to 22 days
Dose Limiting Toxicity (DLT) of a single dose of intravenous recombinant human tumor necrosis factor-α plus liposomal doxorubicin
Toxicity Criteria will be those listed in NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Any grade 3 cytokine release syndrome/acute infusion reaction or allergic and toxicity Grade 3 and above will be considered a DLT except: * Grade 3 toxicities that recover to grade 1 or less within 48 hours after standard supportive treatment. * Grade 4 neutropenia that recovers within 14 days. * Grade 4 thrombocytopenia that recovers within 14 days. * Grade 4 anemia that recovers within 14 days.
Time frame: up to 22 days
Overall tumor response using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Time frame: 4 weeks
Caelyx/doxorubicin plasma levels
Caelyx/doxorubicin plasma levels will be measured at 0, 24, 48 and 192 hours post-dose by fluorimetry (excitation at 470nm, emission 590 nm) after liposomes have been disrupted in 70% ethanol, 0.3 N HCl
Time frame: 0, 24, 48 and 192 hours post-dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Recombinant human TNF-α (Beromun) will be diluted in 250 mL of normal saline with albumin (2 mg/mL) to prevent adherence of the protein to the delivery apparatus. Infusion will be done over 60 minutes, preferably via central venous catheter, including PICC lines.