E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Pancreatic Ductal Adenocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033605 |
E.1.2 | Term | Pancreatic cancer metastatic |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To compare the efficacy of Arm 1 to Arm 2 and Arm 1 to Arm 3 in subjects with 1st-line metastatic pancreatic ductal adenocarcinoma |
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E.2.2 | Secondary objectives of the trial |
•To compare the safety of Arm 1 to Arm 2 and Arm 1 to Arm 3 in subjects with 1st-line metastatic pancreatic ductal adenocarcinoma.
•To compare the rate of immunogenicity of Arm 1 to Arm 2 and Arm 1 to Arm 3 in subjects with 1st-line metastatic pancreatic ductal adenocarcinoma.
•To determine population pharmacokinetics of demcizumab in subjects receiving demcizumab, Abraxane® and gemcitabine in subjects with 1st-line metastatic pancreatic ductal adenocarcinoma. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects must have cytologically or histologically confirmed metastatic pancreatic ductal adenocarcinoma. Prior chemotherapy and/or radiotherapy either in the adjuvant or neoadjuvant setting or for metastatic disease is not allowed.
2. Age >21 years
3. ECOG performance status 0 or 1
4. Measurable disease per RECIST v1.1 |
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E.4 | Principal exclusion criteria |
1. Subjects with a neuroendocrine tumor of the pancreas, an acinar tumor of the pancreas or a pancreatic tumor with mixed histologies.
2. Subjects receiving heparin, warfarin, factor Xa inhibitors or other similar anticoagulants. Note: Subjects may be receiving low-dose aspirin and/or non-steroidal anti-inflammatory agents.
3. Any of the following cardiac-related criteria:
• B-type natriuretic peptide (BNP) value of >100 pg/mL
• Left ventricular ejection fraction (LVEF) <50%
• Peak tricuspid velocity >3.0 m/s on Doppler echocardiogram
• Receiving any medications for cardiac ischemia
• Current evidence of cardiac ischemia
• History of acute myocardial infarction within 6 months prior to randomization
• New York Heart Association Classification II, III, or IV. For subjects to meet class II criteria with mild shortness of breath and/or angina, as defined by the NYHA guidelines, the cardiac etiology of the symptoms should be confirmed by a cardiologist taking 12-lead electrocardiogram, transthoracic Doppler echocardiogram and other studies into consideration, as appropriate.
• History of heart failure or pulmonary hypertension
• Received a total cumulative dose of ≥400 mg/m2 doxorubicin
• Grade ≥2 ventricular arrhythmia |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the hazard of progression using the Investigator assessed progression-free survival time between subjects in Arm 1 and Arm 2 as well as between subjects in Arm 1 and 3 in 1st-line metastatic pancreatic ductaladenocarcinoma. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• To compare the Investigator-assessed RECIST response rate in Arm 1 to Arm 2 and Arm 1 to 3 in subjects with 1st-line metastatic pancreatic cancer.
• To compare the Investigator-assessed RECIST clinical benefit rate (i.e., the rate of complete response + partial response + stable disease) in Arm 1 to Arm 2 and Arm 1 to 3 in subjects with 1st-line metastatic pancreatic ductal adenocarcinoma.
• To compare the Investigator-assessed progression-free survival at 6 months in Arm 1 to Arm 2 and Arm 1 to 3 in subjects with 1st-line metastatic pancreatic ductal adenocarcinoma.
• To compare the Independent Review Facility (IRF)-assessed RECIST response rate and progression-free survival based solely on radiographs in Arm 1 to Arm 2 and Arm 1 to 3 (Optional).
• To determine the half-life, volume of distribution and clearance of demcizumab when combined with Abraxane® and gemcitabine in with subjects with 1st-line metastatic pancreatic ductal adenocarcinoma.
• To compare the safety profile through adverse event monitoring (including attribution of adverse events and serious adverse events [SAEs]), physical examination, vital signs, and clinical laboratory testing as outlined in the Schedule of Assessments between Arm 1 to Arm 2 and Arm 1 to 3 in subjects with 1st-line metastatic pancreatic ductal adenocarcinoma. To compare the incidence of anti-demcizumab antibody development and neutralizing antibody development in subjects with 1st-line locally advanced or metastatic pancreatic ductal adenocarcinoma being treated with Abraxane® and gemcitabine plus demcizumab in Arm 1 to Arm 2 and Arm 1 to 3.
• To compare the median survival in Arm 1 to Arm 2 and Arm 1 to 3 in subjects with 1st-line metastatic pancreatic ductal adenocarcinoma
• The compare the Kaplan Meier estimates of survival at 6, 12, 18 and 24 months in Arm 1 to Arm 2 and Arm 1 to 3 in subjects with 1st-line metastatic pancreatic ductal adenocarcinoma. |
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Australia |
Belgium |
Canada |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |