E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
locally advanced or metastatic pancreatic cancer |
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E.1.1.1 | Medical condition in easily understood language |
cancer of the pancreas that is extensive locally or at spread in distant organs |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033606 |
E.1.2 | Term | Pancreatic cancer non-resectable |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 quality of life scores and times to definitive deterioration of the QOL scores in patients receiving nab-paclitaxel + gemcitabine versus gemcitabine alone using the EORTC QLQ-C30 questionnaire. |
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E.2.2 | Secondary objectives of the trial |
To evaluate in both treatment Arms:
Safety and tolerability profile (NCI-CTCAE v. 4.0) Overall response and duration of response as assessed by imaging (RECIST 1.1) and tumour markers Disease control rates Progression free survival and overall survival Changes in serum CA 19-9 and CEA and composite index CA19-9xCEA Exploratory biomarker analyses by immunohistochemistry, proteomics, microarray and polymerase chain reaction (PCR) studies on tissue, blood and blood products and correlations with outcome. Exploratory hypoxia studies
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Written informed consent (+ optional for TR) must be given according to ICH/GCP and national/local regulations. 2.Patient is at least 18 years of age. 3.Unresectable locally advanced or metastatic pancreatic cancer. 4.Histologically or cytologically confirmed adenocarcinoma of the pancreas. Islet cell neoplasms and neuroendocrine tumours are excluded.. 5.Evaluable or measurable disease, not in a previously irradiated area. 6.Life expectancy of at least 12 weeks. 7.WHO ECOG performance status ≤ 2 8.Adequate organ function. 9.Adequate bone marrow, hepatic and renal function. 10.Acceptable coagulation determined on routine tests (e.g. prothrombin time, partial thromboplastin time, INR, etc, within +/- 15% of normal limits or as per clinical practice). 11.No clinically significant abnormalities in urinalysis. 12.Effective contraception for both male and female patients if applicable. Women of childbearing potential must have negative blood pregnancy test at screening visit.
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E.4 | Principal exclusion criteria |
1.Prior chemotherapy, surgery or other investigational therapy for the treatment for metastatic disease. Adjuvant treatment with gemcitabine or 5-FU is allowed provided at least 6 months have elapsed since completion of the last dose. 2.Major surgery within 4 weeks of the start of the study. 3.Irradiation within 3 weeks prior to study entry. 4.Brain metastasis (known or suspected). 5.Serious medical risk factors involving any of the major organ systems, including high cardiovascular risk including coronary stenting or myocardial infarction in the last year and psychiatric disorders. 6.Known infection with HIV or active infection with hepatitis B or C. 7.History of connective tissue disorders (eg. lupus, scleroderma, arteritis nodosa, etc). 8.History of interstitial lung disease. 9.History of peripheral artery disease. 10.Previous (within 5 years) or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and basal cell carcinoma of the skin. 11.Known allergy or any other adverse reaction to any of the drugs or to any related compound. 12.Use of oral anticoagulants that interfere with the metabolic path of nab-Paclitaxel (cytochrome P450 isoenzymes CYP2C8 and CYP3A4) such as warfarin (Coumadin), rivaroxaban (Xarelto), etc, and the impossibility to switch anticoagulation treatment to low molecular weight heparin. 13.Organ allografts requiring immunosuppressive therapy. 14.Pregnancy or breast-feeding. 15.Medical, social or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent.
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E.5 End points |
E.5.1 | Primary end point(s) |
The deterioration free rate at 3 months, comparatively in both treatment Arms is the study primary variable. The deterioration free survival rate at 3 months is defined as the Kaplan-Meier estimate of the probability of being alive and free of deterioration of the QOL scores at 3 months. The deterioration of the QOL score is a decrease of at least 10 points (minimal clinical important difference) between the score at baseline and any timepoint. The time interval will be calculated from the time of completion of the baseline QOL questionnaire.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
QOL questionnaires will be applied to patients every 4 weeks for a maximum of 12 months. The analysis of the primary (and secondary endpoints) will be performed at the end of the study. |
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E.5.2 | Secondary end point(s) |
Descriptive safety; incidence of treatment-emergent toxicities in both Arms and incidence of dose modifications, interruptions and discontinuations. Dose density and dose intensity. Response and disease control rates - response evaluation will be performed every 8 weeks according to RECIST criteria (CT/MRI scan) Duration of response PFS OS Evolution of the levels of carbohydrate antigen 19 9 (CA19 9) on treatment (q 8 weeks) and composite index. Biomarkers that can be related with benefit to nab-paclitaxel: Potential SNPs , Circulating DNA, Circulating micro-RNA, Selected cytokines (ELISA), hENT1, SPARC, dCK and S100A2 expression (immunohistochemistry/qPCR), Hypoxia studies
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Continuous for safety and dose intensity/density, q8weeks for tumour/response evaluations, continuous for survival, baseline for tissue collection, 3-4 timepoints for blood collection. |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | 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 | 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 | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Comparison between arms (combination nab-paclitaxel+gemcitabine versus gemcitabine alone) only for Q |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Comparison 2 arms (combi nab-paclitaxel+gemci vs gemci alone) only for QOL scores/main endpt |
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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 | 19 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |