E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic pancreatic adenocarcinoma |
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E.1.1.1 | Medical condition in easily understood language |
cancer of the pancreas that has spread to other parts of the body |
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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 | 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 |
The primary objective of the trial is to investigate the outcome of sequential administration of ABX combined with GEM (ABX/GEM) in patients with metastatic PDAC in terms of progression-free survival. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to evaluate the clinical aspects (including safety, response, and overall survival) and pharmacological differences between ABX/GEM administered concomitantly and sequentially; to assess quality of life (QoL) and health economics (HE) in both concomitant ABX/GEM and sequential ABX/GEM regimens; to explore biomarkers for identifying patient subgroups who are more likely to benefit from treatment using tumour tissue and blood samples collected prospectively. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Aged ≥ 18 years old • Signed informed consent and ability to comply with the protocol • Histologically or cytologically confirmed metastatic PDAC • Radiologically confirmed stage IV disease and measurable disease by RECIST version 1.1; baseline tumour assessments and measurements must be done within 28 days prior to randomisation • Karnofsky performance status ≥70% • Life expectancy >12 weeks from the date of screening assessment • Adequate bone marrow function o Absolute neutrophil count (ANC) ≥1.5 x 10^9 /L o Haemoglobin (Hb) ≥ 100 g/L o Platelets ≥100 x 10^9 /L o White blood cell count (WBC) ≥ 3 x 10^9 /L • Adequate liver function o Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤2.5 x upper limit of normal range (ULN) o Total bilirubin <1.5 x ULN • Adequate renal function defined as a serum creatinine ≤1.5 x ULN or calculated creatinine clearance by Cockcroft-Gault of ≥50 mL/min • Received no prior systemic therapy for metastatic disease • Prior adjuvant chemotherapy (with GEM or any other drug/s) is allowed if completed at least 6 months previously • Prior radiotherapy is allowed as long as there is measurable disease which has not been irradiated • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, completion of QoL and HE questionnaires and other study procedures • Confirmation of tumour tissue sample collected within 12 weeks prior to randomisation and blood to be taken prior to randomisation • Women of child-bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if age ≤55 years or 12 months if age >55 years, must have a negative serum or urine pregnancy test within 14 days prior to randomisation • All WCBP, all sexually active male patients, and all partners of patients must agree to use effective contraception methods throughout the study and for 30 days after the final dose of study drug for WCBP and for up to 6 months after treatment for male patients |
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E.4 | Principal exclusion criteria |
The presence of any of the following will exclude patients: • Patients with operable or locally advanced PDAC • Other invasive malignancies diagnosed within the last 5 years, except non-melanoma skin cancer and localized cured prostate cancer • Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial. Examples include, but are not limited to: o Patients who have had a venous thromboembolic event who are not appropriately anticoagulated or have had a significant bleeding episode in the 3 weeks prior to randomisation o Patients with symptoms of severe chronic obstructive airways disease or significant shortness of breath at rest AND have an FEV1<1.0 L within the last 6 months o Patients with a history of interstitial lung disease, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis, cystic fibrosis or bronchiectasis o Patients with uncontrolled ischaemic heart or other cardiovascular event (myocardial infarction (MI), new angina, stroke transient ischaemic attack (TIA), or new congestive cardiac failure (CCF)) within the last 6 months o Patients with stable but significant cardiovascular disease defined by heart failure (New York Heart Association Functional Classification (NYHF) III or IV) or frequent angina o Presence of active infection o Cirrhotic liver disease, known chronic active or acute hepatitis B, or hepatitis C o Known allergy or hypersensitivity to GEM or ABX
• Women who are pregnant, plan to become pregnant or are lactating • Use of oral anti-oxidant supplements: beta-carotene, selenium, lutein, zeaxanthin, lycopene, pycnogenol, fernblock, omega-3S, vitamin C, vitamin E, astaxanthin
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure is progression free survival. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Progression-free survival (PFS): PFS will be calculated from the date of randomisation to the date of clinical/radiological progression or death from any cause, whichever occurs first; surviving patients without progression will be censored at the date of their last clinical follow-up at the time of analysis.
Progression is defined as ANY of the following: • Radiological progression according to RECIST version 1.1 • Death due to disease without prior objective documentation of progression • Global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression • Unequivocal progression of existing non-target lesions, in the opinion of the investigator (in this circumstance an explanation must be provided) |
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E.5.2 | Secondary end point(s) |
Secondary end point measures are safety, response, overall survival, quality of life and health economics. In addition, evaluation of pharmacological differences in scheduling of ABX and GEM will be undertaken to explore biomarkers for identifying patient subgroups more likely to benefit from treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
These will be investigated at the end of the trial, which is when the last patient recruited has had follow-up for 12 months following their randomisation date. |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
The same medicinal products but a different dosing schedule. |
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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 | 20 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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All patients should be followed up for at least 1 year from the date they were randomised. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 | 1 |