Study of Ibrutinib vs Placebo, in Combination With Nab-paclitaxel and Gemcitabine, in the First Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma (RESOLVE)
- Conditions
- Metastatic Pancreatic Adenocarcinoma
- Interventions
- Registration Number
- NCT02436668
- Lead Sponsor
- Pharmacyclics LLC.
- Brief Summary
This is a phase 3 study to evaluate the efficacy of ibrutinib in combination with nab-paclitaxel and gemcitabine for the first line treatment of patients with metastatic pancreatic adenocarcinoma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 430
-
Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma.
-
Stage IV disease diagnosed within 6 weeks of randomization
-
Adequate hematologic function:
- Absolute neutrophil count (ANC) ≥1.5 x 109/L
- Platelet count ≥100 x 109/L
- Hemoglobin ≥9 g/dL
-
Adequate hepatic and renal function defined as:
- AST and/or ALT ≤5.0 x upper limit of normal (ULN) if liver metastases, or ≤3 x ULN without liver metastases
- Alkaline phosphatase <3.0 x ULN or ≤5.0 x ULN if liver or bone metastases present
- Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin, such as hemolysis)
- Estimated Creatinine Clearance ≥30 mL/min
-
PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN
-
KPS ≥70.
-
Eastern Cooperative Oncology Group (ECOG) 0-1
- Prior therapies: BTK inhibitor, radiotherapy, radiotherapy in the adjuvant setting, or cytotoxic chemotherapy for primary disease of pancreatic adenocarcinoma.
- Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma
- Known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement).
- Major surgery within 4 weeks of first dose of study drug.
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- Treatment with a strong cytochrome P450 (CYP) 3A inhibitor.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Nab-paclitaxel Placebo daily in combination with: Nab-paclitaxel and gemcitabine Placebo Gemcitabine Placebo daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib Ibrutinib Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib Nab-paclitaxel Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine Ibrutinib Gemcitabine Ibrutinib daily in combination with: Nab-paclitaxel and gemcitabine
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Results at an overall median follow-up of 24.87 months PFS is defined as the time from the date of randomization until disease progression per RECIST 1.1 criteria assessed by investigator, or death from any cause, whichever occurs first.
Overall Survival (OS) Results at an overall median follow-up of 24.87 months OS, is defined as the time from date of randomization until date of death from any cause.
- Secondary Outcome Measures
Name Time Method Clinical Benefit Response Results at an overall median follow-up of 24.87 months Subject achieved a ≥50% reduction in pain intensity (Memorial Pain Assessment Card \[MPAC\]) or analgesic consumption, or a 20-point or greater improvement in KPS for a period of at least 4 consecutive weeks, without showing any sustained worsening in other parameters.
OR Subject was stable on all of the aforementioned parameters, and showed a marked, sustained weight gain (≥7% increase maintained for ≥4 weeks) not due to fluid accumulation (Burris 1997).Patient-reported Outcome (PRO) by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). Results at an overall median follow-up of 24.87 months Unit is the month: TUDD1 - the time between random \& 1st occurrence of a decrease in QLQ-C30 score ≥10 pts w/o improvement in QoL score of ≥10 points or any further QoL data due to deterioration. The proportion of subjects who met the "responder" criteria prior to subsequent anticancer therapy initiation. Response defined as achievement of a ≥50% reduction in MPAC visual analog scale which measures pain intensity or analgesic consumption, or a ≥20-point improvement from baseline in KPS sustained for a period of ≥ 4 consecutive weeks without showing any sustained worsening from baseline in any of the other parameters OR Subject stable on all parameters (pain and KPS), \& showed a marked, sustained weight gain (≥7% increase from baseline maintained for ≥4 weeks) not due to fluid accumulation.
Overall Response Rate Results at an overall median follow-up of 24.87 months ORR is defined as the percentage of subjects who achieve a complete response or partial response, based on investigator assessment according to RECIST 1.1.
Rate of Venous Thromboembolic Events (VTE) Results at an overall median follow-up of 24.87 months The VTE rate is defined as percentage of subjects with Venous thromboembolic events (SMQ) per investigator assessment.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine. Results at an overall median follow-up of 24.87 months This is a measure of percentage of subjects with Treatment Emergent Adverse Events Grade 3 or above collected Up to 30 days after the last participating subject discontinues study drug.
Carbohydrate Antigen 19-9 (CA19-9) Response Results at an overall median follow-up of 24.87 months The CA19-9 response rate is defined as the percentage of subjects with a decline of 20%, 90%, and other thresholds considered clinically meaningful, from baseline. This is a percentage of patients with \> or = 60% reduction from baseline.
Trial Locations
- Locations (86)
Oncology Specialties, PC; Clearview Cancer Institute
🇺🇸Huntsville, Alabama, United States
Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
St. Mary's Medical Center
🇺🇸Daly City, California, United States
Eastern Connecticut Hematology/Oncology Assoc.
🇺🇸Norwich, Connecticut, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Norwalk Hospital
🇺🇸Norwalk, Connecticut, United States
Bethesda Memorial Hospital
🇺🇸Boynton Beach, Florida, United States
University Cancer & Blood Center, LLC
🇺🇸Athens, Georgia, United States
Northwest Georgia Oncology Centers, PC
🇺🇸Marietta, Georgia, United States
Ingalls Memorial Hospital Cancer Research Center
🇺🇸Harvey, Illinois, United States
Joliet Oncology-Hematology Associates, LTD
🇺🇸Joliet, Illinois, United States
Our Lady of the Lake Physician Group
🇺🇸Baton Rouge, Louisiana, United States
Berkshire Hematology Oncology Services at Berkshire Medical Center Cancer and Infusion Center
🇺🇸Pittsfield, Massachusetts, United States
Sparrow Regional Cancer Center
🇺🇸Lansing, Michigan, United States
Saint Joseph Mercy Health System
🇺🇸Chelsea, Michigan, United States
Investigative Clinical Research of Indiana
🇺🇸Indianapolis, Indiana, United States
The Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Penn State University Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Scott & White Memorial Hospital
🇺🇸Temple, Texas, United States
MultiCare Health System Institute for Research and Innovation
🇺🇸Tacoma, Washington, United States
Wenatchee Valley Hospital & Clinics
🇺🇸Wenatchee, Washington, United States
ULB Hôpital Erasme
🇧🇪Bruxelles, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
C. H. U. Sart Tilman
🇧🇪Liège, Belgium
Centre Antoine Lacassagne
🇫🇷Nice cedex 02, Alpes Maritimes, France
Centre Paul Strauss
🇫🇷Strasbourg cedex, Bas Rhin, France
Hôpital Nord Franche Comté
🇫🇷Doubs, Montbeliard, France
Hôpital de la Timone
🇫🇷Marseille cedex 5, Bouches-du-Rhône, France
Centre Georges François Leclerc
🇫🇷Dijon cedex, Côte-d'Or, France
CHU de Toulouse - Hôpital Rangueil
🇫🇷Toulouse Cedex 9, Haute Garonne, France
CHU Besançon - Hôpital Jean Minjoz
🇫🇷Besançon, Doubs, France
Groupe Hospitalier Saint André - Hôpital Saint André
🇫🇷Bordeaux, Gironde, France
Hôpital Saint-Antoine
🇫🇷Paris cedex 12, Paris, France
CHU Poitiers - Hôpital la Milétrie
🇫🇷Poitiers Cedex, Vienne, France
Groupe Hospitalier Pitie-Salpetriere
🇫🇷Paris, France
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Baden Wuerttemberg, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Baden Wuerttemberg, Germany
Klinikum der Johann Wolfgang Goethe-Universitaet
🇩🇪Frankfurt, Hessen, Germany
Universitaetsklinikum Koeln
🇩🇪Koeln, Nordrhein Westfalen, Germany
Universitaetsklinikum Leipzig AoeR
🇩🇪Leipzig, Sachsen, Germany
Gemeinschaftspraxis Haematologie und Onkologie
🇩🇪Dresden, Sachsen Anhalt, Germany
Onkologische Schwerpunktpraxis Kurfuerstendamm
🇩🇪Berlin, Germany
Azienda Ospedaliero Universitaria Ospedali Riuniti
🇮🇹Ancona, Italy
Azienda Ospedaliero Universitaria San Martino
🇮🇹Genova, Italy
IEO Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Ospedaliera Ospedale Niguarda Ca' Granda
🇮🇹Milano, Italy
IOV - Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
IRCCS Ospedale Casa Sollievo della Sofferenza
🇮🇹San Giovanni Rotondo, Italy
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Jeollanam-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Hospital del Mar
🇪🇸Barcelona, Spain
Specialist
🇪🇸Barcelona, Spain
ICO l´Hospitalet - Hospital Duran i Reynals
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Clinico Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
The Clatterbridge Cancer Centre
🇬🇧Liverpool, Merseyside, United Kingdom
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom
The Christie
🇬🇧Manchester, Greater Manchester, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
Broomfield Hospital
🇬🇧Chelmsford, Essex, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, Surrey, United Kingdom
Arizona Center for Cancer Care
🇺🇸Avondale, Arizona, United States
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
Gibbs Cancer Center
🇺🇸Spartanburg, South Carolina, United States
Grand Hôpital de Charleroi
🇧🇪Gilly, Belgium
Mary Bird Perkins Cancer Center
🇺🇸Baton Rouge, Louisiana, United States
Derriford Hospital
🇬🇧Plymouth, Devon, United Kingdom
Florida Hospital Tampa
🇺🇸Tampa, Florida, United States
Center for Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States
Nebraska Medicine - Peggy D. Cowdery Patient Care Center
🇺🇸Omaha, Nebraska, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States