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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: PEGPH20


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Maximally Tolerated Dose<br>To identify the maximally tolerated dose (MTD) of PEGPH20. | Drug: PEGPH20<br>* PEGylated Recombinant Human Hyaluronidase<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximally Tolerated Dose (MTD) of PEGPH20 when given to patients with cancer | The PEGPH20 monotherapy MTD is the highest dose at which no more than one of six evaluable patients experience Dose-Limiting Toxicity (DLT) | To be evaluable for MTD determination, a patient must have completed the Cycle 1 study drug doses and the associated assessments for safety and toxicity evaluation | 
| Safety endpoints including assessment of both serious and non-serious AEs | All safety data will be evaluated using the NCI CTCAE scoring system (version 4.0) | From Day 1 of Treatment Cycle 1, thru to Follow-up (within 28 days after last dose of PEGPH20) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PEGPH20, PEGylated Recombinant Human Hyaluronidase, Metastatic or Locally Advanced Solid Tumors