Study of PEGPH20 With Initial Dexamethasone Premedication Given Intravenously to Patients With Advanced Solid Tumors

A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of PEGPH20 With Initial Dexamethasone Premedication Given Intravenously to Patients With Advanced Solid Tumors

This is an open-label, multicenter, dose-escalation, safety, tolerability, pharmacokinetic and pharmacodynamic study in patients with advanced solid tumors.

A study of PEGylated recombinant human hyaluronidase (PEGPH20) administered on a twice weekly schedule for 28 days followed by a weekly dosing schedule in patients with advanced solid tumors who have either failed to respond to standard therapy or for whom no standard therapy exists.

Inclusion Criteria:

• Written, signed, IRB-approved informed consent form.
• Pathologic (histologic or cytologic) confirmation of metastatic or locally advanced solid tumor.
• Patients must have a pathologically documented, definitively diagnosed, advanced solid tumor that is refractory to standard treatment, for which no standard therapy is available or the patient refuses standard therapy.
• One or more tumors measurable by RECIST criteria.
• Karnofsky performance status ≥ 70%.
• Ejection fraction ≥ 50%, determined by echocardiogram.
• Life expectancy at least 3 months.
• Age ≥ 18 years.
• Acceptable organ function; normal hepatic, renal and hematopoietic function.
• Negative serum or urine pregnancy test result in women of childbearing potential.

Exclusion Criteria:

• Known brain metastasis.
• New York Heart Association Class III or IV cardiac disease, myocardial infarction within 6 months of enrollment, or cardiac arrhythmia requiring medical therapy.
• Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy.
• Patients with uncontrolled diabetes (requiring medication change within 30 days of screening), or requiring insulin therapy.
• Heparin therapy.
• Known infection with HIV, hepatitis B, or hepatitis C.
• Known allergy to hyaluronidase.
• Women currently breast feeding.