E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Pancreatic Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic Pancreatic Cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033605 |
E.1.2 | Term | Pancreatic cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase 1b
•To assess the safety and tolerability, and determine a safe dose of PEGPH20 to use in combination with the approved dose of gemcitabine
Phase 2 (in EU sites)
• To compare Overall Survival (OS) in gemcitabine plus PEGPH20 versus gemcitabine plus placebo treatment groups from the time of randomization. |
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E.2.2 | Secondary objectives of the trial |
•To compare the percent of patients in the gemcitabine plus PEGPH20 vs. gemcitabine plus placebo treatment groups that demonstrate a decrease in CA19-9 of ≥ 75% , ≥ 50% and ≥ 25%
• To assess the treatment effect by: ORR,DOR and PFS in all patients
• Monitor changes in pain assessment score in all patients
• To access tumor burden by RECIST 1.1 and CHOI criteria
• To assess OS and PFS at 3, 6, 9, and 12 months from the time of randomization
• To characterize PEGPH20 plasma PK
• To explore pharmacodynamic endpoints such as HA catabolites in serum and urine. Archived biopsies and optional pre- and post-dose tumor biopsiesfor staining of HA, tumor DCE-MRI and FDG-PET will also explore these endpoints
• To determine whether: 1) intensity of tumor-associated HA staining, 2) DCE-MRI perfusion, and/or 3) FDG-PET perfusion, anatomic data and metabolic activity, are associated with a decrease in CA19-9 levels, or other criteria. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with histologically confirmed Stage IV adenocarcinoma of the pancreas previously untreated for metastatic disease
• One or more metastatic tumors measurable on CT scan per RECIST 1.1 criteria
• Baseline CA19-9 of ≥ 100 U/mL in the absence of biliary obstruction or other physiological process unrelated to the tumor that may cause an elevation in CA19-9 levels
• Karnofsky performance status ≥ 70%
• Life expectancy of at least 3 months
• Age ≥ 18 years
• Signed, written IRB/EC-approved informed consent
• A negative serum pregnancy test, if female
• 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)
− Alkaline phosphatase ≤ 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 ≥ 150,000 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
• Baseline ejection fraction done by MUGA Scan ≥ 50%
• 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 |
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E.4 | Principal exclusion criteria |
• Known brain metastasis
• New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 12 months, or cardiac arrhythmia requiring medical therapy
• 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 |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
As per Study schedule of events (included in the Study protocol) |
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E.5.2 | Secondary end point(s) |
• The CA19-9 response rate (also defined as the number of patients achieving a ≥25%, ≥50% or ≥75% decline in CA19-9 from baseline divided by the total number of patients in the ITT Population). The proportion of patients that achieved a ≥25%, ≥50% or ≥75% decline in CA19-9 from baseline along with the 95% confidence interval will be reported for each treatment group. The Fishers exact test will be used to test for treatment group differences.
• ORR as defined by RECIST 1.1 criteria will be evaluated. The objective response rate (complete response [CR] + partial response [PR] + stable disease [SD]), as well as the rates for the individual categories of response (i.e., CR, PR, SD, and PD), will be estimated by the percentage of ITT patients achieving these criteria. The proportion of patients that responded along with the 95% confidence interval will be reported for each treatment group. The Fishers exact test will be used to test for treatment group differences in the objective response rate. Response will also be assessed using CHOI criteria.
• DOR is defined as the interval from the demonstration of a CR, PR or SD to the earliest documented evidence of recurrent or progressive disease, or the date of death due to any cause, whichever occurs first. DOR will be reported using a Kaplan-Meier estimate (median and 95% confidence interval) for each treatment group only on patients achieving a response (CR, PR, or SD). The log-rank test will be used to test for treatment group differences.
• PFS is defined as the interval from the date of randomization to the earliest date of documented evidence of recurrent or progressive disease, or the date of death due to any cause, whichever occurs first. PFS 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.
• Change in pain assessment score will be displayed by use of descriptive statistics overtime (monthly) by treatment group.
• OS and PFS rates at Months 3, 6, 9, 12 will be displayed using descriptive statistics (number and percent) by treatment group. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Phase 1b (not in EU sites) |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Phase 1b - open label, Phase 2-double blind |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
PEGPH20+gemcitabine vs. Placebo+gemcitabine |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Czech Republic |
Hungary |
Romania |
Russian Federation |
Slovakia |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |