Safety, Pharmacokinetics and Efficacy of AXP107-11 in Combination With Standard Gemcitabine (Gemzar®) Treatment in Patients With Locally Advanced or Metastatic, Unresectable, Adenocarcinoma of the Pancreas, Stage III-IV: A Prospective, Open Label, Multi-centre, Sequential Phase Ib/IIa Study
AXP107-11
Adénocarcinome+9
+ Carcinome
+ Maladies du système digestif
Étude thérapeutique
Résumé
Date de début de l'étude : 1 novembre 2010
Date à laquelle le premier participant a commencé l'étude.The annual incidence rate of pancreatic cancer is almost identical to the mortality rate. Despite a low incidence rate, pancreatic cancer is the fourth leading cause of cancer mortality in both men and women. Today is the only potentially curative option of these patients complete surgical resection. However, a majority of the patients (up to 80%) are not eligible for surgery for different reasons. Today is gemcitabine the accepted first-line treatment for these patients. Recent advances in the management of pancreatic cancer suggest that gemcitabine may be improved by combining it with other anticancer drugs. One attractive therapeutic option is genistein. Genistein appears to sensitize tumors to chemotherapy both by targeting the tumor cells and also by targeting components of the tumor microenvironment. However, the limited bioavailability of genistein in its known crystalline form has led to difficulties in attaining adequate plasma concentration, resulting in limited application and dissemination in the clinical setting. To overcome this limitation, a novel crystalline form of genistein with improved pharmaceutical properties is being used. AXP107-11, a crystalline salt of genistein has improved physiochemical properties (solubility, dissolution rate, bioavailability) as compared to the known crystalline form of genistein. In this study, AXP107-11, will be investigated alone and in combination with gemcitabine in patients with pancreatic cancer.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.44 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.À partir de 18 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
Inclusion Criteria: 1. Age ≥ 18 years at the time of signing the informed consent 2. Histologically confirmed adenocarcinoma of the pancreas 3. Metastatic or locally advanced, unresectable disease stage III-IV. 4. Measurable disease according to the international criteria proposed by the Response Evaluation Criteria in Solid tumors (RECIST) for target lesions 5. Karnofsky Performance Status ≥ 70 at study entry (Appendix 18.4). 6. Life expectancy of more than three months 7. Negative pregnancy test for female patients 8. For fertile women, willingness to perform double-barrier contraception during study and for four weeks after last treatment 9. Able and willing to sign the informed consent form Exclusion Criteria: 1. Previous or ongoing severe supraventricular or ventricular arrhythmia 2. Previous or ongoing coagulation or bleeding disorder (PTT \> 1.5 x ULN) 3. HIV infection 4. Known hypersensitivity to any component of the AXP107-11 formulation or gemcitabine 5. Previous or ongoing significant liver pathology (other than metastases) and/or liver function disorders 6. Previous or ongoing significant chronic renal dysfunction 7. Previous or ongoing malignancy other than pancreatic cancer \< five years prior to enrolment, except basal cell carcinoma treated locally 8. Cardiovascular disease, New York Heart Association (NYHA) classification III or IV16 9. Severe pulmonary obstructive or restrictive disease 10. Acute or chronic inflammation (autoimmune or infectious) 11. Significant active/unstable non-malignant disease likely to interfere with study assessments 12. Laboratory tests (hematology, chemistry) outside specified limits: * WBC ≤ 3 x 10³/mm³ * ANC ≤ 1.5 x 10³/mm³ * Platelets ≤ 100.000/mm³ * Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l) * PT/PTT \> 1.5 x ULN * Serum creatinine \> 130 μmol/l) or clearance \< 60 ml/min * AST and/or ALT \> 3 x ULN with the exception of patients with liver metastasis (\> 5 x ULN) * Alkaline phosphatase \> 3 x ULN * Total bilirubin \> 3 x ULN 13. Immunotherapy within six weeks prior to enrolment. 14. Any chemotherapeutical treatment for pancreatic adenocarcinoma before enrolment 15. Any radiotherapy for pancreatic adenocarcinoma before enrolment except for treatment of bone metastases if target lesions are not included in the irradiated field 16. Major surgery within four weeks prior to enrolment 17. Pregnant or nursing woman 18. Participations in other interventional clinical study within four weeks of enrolment
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.Un seul groupe d'intervention est désigné dans cette étude
Cette étude ne comporte pas de groupe placebo.
Groupes de traitement
Groupe I
ExpérimentalObjectifs de l'étude
Objectifs principaux
Objectifs secondaires
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 2 sites
Dept. of Clinical Science, Intervention and Technology, Div. of surgery, Karolinska University Hospital, Huddinge
Stockholm, SwedenOuvrir Dept. of Clinical Science, Intervention and Technology, Div. of surgery, Karolinska University Hospital, Huddinge dans Google MapsDept. of Oncology-Pathology, Karolinska University Hospital, Solna
Stockholm, Sweden