E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally-advanced Pancreatic Adenocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
Pancreatic cancer that is apparent only in and around the pancreas yet cannot be surgically removed
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
The main objective of the trial is to compare overall survival (OS) of subjects with locallyadvanced pancreatic cancer (LAPC) who are randomized to receive dasatinib added to standard of care (gemcitabine [GEM]) versus standard of care (GEM) plus placebo |
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E.2.2 | Secondary objectives of the trial |
The secondary objective:
• To compare progression-free survival (PFS) in subjects receiving dasatinib added to standard of care (GEM) versus standard of care (GEM) plus placebo
• To compare safety in subjects receiving dasatinib added to standard of care (GEM) versus standard of care (GEM) plus placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria
• Histologic or cytologic documentation of adenocarcinoma of the pancreas
• Unresectable disease due to local extension or invasion, for example:
− Tumor extension precluding resection, eg, to
mesenteric or retroperitoneal structures,vascular
encasement, etc, or
− Lymph node involvement beyond the surgical field
• Recovery from toxicity of previous procedures that establish diagnosis of locally-advanced disease (patients with previous pancreatic resection are excluded)
• ECOG PS 0 or 1
• Adequate organ function:
− Absolute neutrophil count ≥ 1,500/μL
− Platelet count ≥ 100,000/μL
− Bilirubin ≤ 2.0 X upper limit of normal (ULN)
− Creatinine ≤ 1.5 mg/dL
− Aspartate transaminase ≤ 2.5 X ULN |
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E.4 | Principal exclusion criteria |
Exclusion Criteria
• Evidence of metastatic disease based on symptoms, laboratory values, or imaging studies ≤ 21 days prior to the first dose of IMP
• Previous radiotherapy or chemoradiotherapy
• History of or current pleural effusion (any cause, ≥ Grade 1) within 6 months prior to the first dose of IMP.
An equivocal finding at the costophrenic angle is allowed
• History of significant cardiovascular disease or the
following events within 6 months prior to the first dose of IMP: coronary infarction, life-threatening arrhythmia, or QTc prolongation > 470 ms
• Clinically significant bleeding disorder or coagulopathy (eg, von Willebrand’s disease)
• Requirement for a concomitant medication that is a strong inhibitor of Cytochrome P450 (CYP) 3A4 |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Overall survival: The primary objective of this trial is to compare OS of subjects receiving standard of care treatment (GEM) plus dasatinib versus GEM plus placebo. Subjects will be followed after discontinuation of study
therapy to record time to death. The final analysis will be conducted after 135 subject deaths. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final analysis will be conducted after 135 subject deaths. |
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E.5.2 | Secondary end point(s) |
Progression Free Survival: Subjects will be assessed by imaging after every 2 cycles (ie, Weeks 8, 16, 24, etc). Progression events will be investigator determined according to Response
Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria. Worsening pain, fatigue, ECOG PS, and/or CA19-9 are not by themselves considered evidence of disease progression
but may be considered in the investigator’s evaluation of disease.
• Safety: All AEs will be recorded with onset date, resolution or stabilization date, severity grade, and relatedness to study treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Progression Free Survival: every 2 cycles
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
CA19-9 response will be analyzed |
|
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Austria |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Ireland |
Italy |
Poland |
Romania |
Russian Federation |
South Africa |
United Kingdom |
United States |
|
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
|
The End of Trial Date will be determined by the sponsor after at least 135 death events have occurred. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |