Metastatic Pancreatic Cancer MedDRA version: 14.1 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: PEGylated Recombinant Human Hyaluronidase
Product Code: PEGPH20
Pharmaceutical Form: Solution for injection
Current Sponsor code: PEGPH20
Other descriptive name: PEGylated recombinant hu
H201
rHuPH20
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 3.5-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the
Sponsors
Halozyme, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Newly diagnosed, previously untreated, histologically confirmed Stage IV pancreatic ductal adenocarcinoma with documented disseminated neoplasm to the liver and/or the lung. Prior to enrollment, confirmation of the following must be obtained: -Pathology report of the tissue biopsy reviewed and approved by the Sponsor medical monitor -Available tumor tissue block or a minimum of 5 unstained core biopsy slides that meet specific tissue sample requirements (see Study Laboratory Manual). Note: Fine needle aspirates (FNA) or brushing biopsies will not be acceptable. • One or more metastatic tumors measurable on CT scan per RECIST 1.1 criteria • Karnofsky Performance Status = 70% • Life expectancy of at least 3 months • Age = 18 years • Signed, written IRB/EC-approved Informed Consent Form • A negative serum pregnancy test, if female • Ejection fraction = 50% by either Echocardiogram (Echo) or multi-gated acquisition (MUGA) Scan • Acceptable liver function: - Bilirubin = 1.5 times upper limit of normal - AST (SGOT) and ALT (SGPT) = 2.5 times upper limit of normal, (if liver metastases are present, then = 5 times upper limit of normal is allowed) • Acceptable renal function: - Serum creatinine within normal limits, OR calculated creatinine clearance = 40 mL/min/1.73 m2 for patients with creatinine levels above normal • Acceptable hematologic status: - ANC = 1,500 cells/mm3 - Platelet count = 100,000 plt/mm3 - Hemoglobin = 9 g/dL • Acceptable coagulation status: - PT/INR within normal limits or INR 2.0-3.0 if on warfarin - PTT within normal limits, or within 1.2xULN if on warfarin • For men and women of child-producing potential, agreement to use an effective contraceptive method from the time of screening and throughout their time on study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Locally advanced Pancreatic Ductal Adenocarcinoma (PDA) • Known central nervous system involvement or brain metastases • New York Heart Association Class III or IV cardiac disease (Appendix C), or myocardial infarction within the past 12 months • Active, uncontrolled bacterial, viral, or fungal infection requiring systemic therapy • Known infection with HIV, hepatitis B, or hepatitis C • Known allergy to hyaluronidase • Women currently pregnant or breast feeding • Heparin therapy administered IV • Intolerant to dexamethasone • History of another primary cancer within the last 3 years with the exception of skin cancer (other than melanoma) or curatively-treated cervical carcinoma in-situ • Any other disease, metabolic dysfunction, physical examination finding or clinical laboratory finding that leads to reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, that may affect the interpretation of the results or render the patient at high risk from treatment complications • Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the patient unsuitable for the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1b •To assess the safety and tolerability, and select a safe dose of PEGPH20 in combination with gemcitabine Phase 2 •To compare the Overall Survival (OS) of PEGPH20 in combination with gemcitabine versus gemcitabine in combination with placebo in patients with previously untreated Stage IV pancreatic cancer.;Timepoint(s) of evaluation of this end point: As per Study schedule of events (included in the Study protocol);Secondary Objective: Phase 1b • To characterize plasma pharmacokinetics of PEGPH20 when used in combination with gemcitabine • To assess the Objective Response Rate (ORR) by RECIST 1.1 criteria • To assess PEGPH20 pharmacodynamic activities including hyaluronan catabolites in serum and urine, HA staining changes in tumor biopsies, as well as PEGPH20 effect on vascular perfusion and metabolic activities of the tumor using DCE-MRI and FDG-PET/CT • To explore the PEGPH20 effect on CA19-9 changes in relation to: 1) intensity of tumor-associated HA staining, 2) DCE-MRI perfusion, and/or 3) FDG-PET/CT perfusion, anatomic data and metabolic activity Phase 2 • To compare the change in CA19-9 levels in the PEGPH20 plus gemcitabine with gemcitabine plus placebo treatment groups • To compare the Objective Response Rate (ORR) between the two groups by RECIST 1.1 criteria • To compare Progression-free Survival (PFS) between the two groups;Primary end point(s): •For the Phase 1b portion of the study, the primary objectives are to assess safety, tolerability, and to determine a safe dose of PEGPH20 to use in combination with the approved dose of gemcitabine for Phase 2. • For Phase 2, OS is the primary endpoint. OS is defined as the interval from the date of randomization to the date of death due to any cause. OS will be reported using a Kaplan-Meier estimate (median and 95% confidence interval) for each treatment group for all patients in the ITT population. The log-rank test will be used to test for treatment group differences. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The distributions of the change in CA19-9 from baseline to Week 8 of Cycle 1 between the groups will be compared. Additionally, the percent of patients achieving a = 25%, = 50%, and = 75% decline in CA19-9 from baseline to Week 8 of Cycle 1 and their 95% confidence intervals will be calculated for each treatment group. • An objective response as defined by RECIST 1.1 criteria will be evaluated. The proportion of patients achieving an objective response (the objective response rate [ORR]) (either a complete response [CR] or a partial response [PR]), and its 95% confidence interval will be estimated for each group. The Fisher’s exact test will be used to test the difference in the ORR between groups. • PFS will be analyzed using the ITT population. The hazard ratio (PEGPH20/placebo) and its 95% confidence interval will be estimated using a Cox proportional hazards regression model. Kaplan-Meier curves will be calculated for each group and the median progression free survivals estimated. • Duration of Response (DOR) is defined as the interval from the demonstration of an objective response (CR+PR) to the earliest of documented evidence of recurrent or progressive disease or the date of death due to any cause. DOR will be described using Kaplan-Meier curves for patients in each treatment group who achieved an objective response. • The proportions of patients achieving a complete response [CR], a partial response [PR], and who have stable disease [SD] and their 95% confidence intervals will be calculated and reported. • The proportion of patients in each group achieving an objective response as defined by the CHOI criteria and their 95% confidence intervals will be calculated. • Change in pain assessment score will be reported using descriptive statistics, by time and treatment group. • Estimates of OS and PFS at Months 3, 6, 9, and 12 will be calculated from the Kaplan-Meier curves, and reported by treatment group.;Timepoint(s) of evaluati | — |
Countries
Czech Republic, Hungary, Romania, Russian Federation, Slovakia, United States
Contacts
Public ContactSam Dychter
Halozyme, Inc
Outcome results
None listed