QOLINPAC

Two arm, comparative, randomized, crossover, open label, multicenter.

Primary

To compare quality of life scores and times to definitive deterioration in patients receiving nab-paclitaxel + gemcitabine versus gemcitabine alone using the EORTC QLQ-C30 questionnaire.

Secondary

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 (PFS) and overall survival (OS)
• Changes in serum CA 19-9 and CEA and composite index CA19-9xCEA
• Exploratory biomarker and hypoxia studies on blood products and tumour tissues with possible correlations with efficacy outcomes.

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 (PS) ≤ 2
8. Adequate organ function.
9. Adequate bone marrow, hepatic and renal function:
   1. Hemoglobin > 8.0 g/dL, absolute neutrophil count > 1.5 x 109/L, platelet count > 100 x 109/L
   2. ALAT, ASAT < 2.5 x ULN, up to &lt; 5 x ULN in case of liver involvement
   3. Total bilirubin < 2 x ULN. No jaundice.
   4. Serum creatinine < 1.5 x ULN and /or calculated creatinine clearance
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.

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.

Patients will be randomized to receive nab-paclitaxel + gemcitabine or gemcitabine alone

Study period: end recruitment: Oct 2015

U.Z. Leuven (University Hospital Leuven) Digestive Oncology Unit

UZ Leuven; AZ Delta - Campus Wilgenstraat Roeselare; AZ Klina - Brasschaat; AZ Maria Middelares Gent; AZ Sint Maarten Mechelen; AZ St-Lucas Brugge; AZ Turnhout - Campus St-Elisabeth; CHC St-Joseph Liege; CHR Citadelle Liege; CHU de Charleroi - Site Vésale; CHU Sart-Tilman Liege; Clinique Ste-Elisabeth Namur; Cliniques Universitaires Saint Luc BXL; HHZH Lier; Hôpital Erasme; OLV Ziekenhuis Aalst; UZ Antwerpen; UZ Gent;