Clinical trial NCT02436668: Study of Ibrutinib vs Placebo, in Combination With Nab-paclitaxel and Gemcitabine, in the First Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma (RESOLVE)
Official title: A Randomized, Multicenter, Double-blind, Placebo-controlled, Phase 3 Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib in Combination With Nab-paclitaxel and Gemcitabine Versus Placebo in Combination With Nab-paclitaxel and Gemcitabine, in the First Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Pancreatic Adenocarcinoma
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
First posted: 2015-05-07
Enrollment: 430
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma.
2. Stage IV disease diagnosed within 6 weeks of randomization
3. Adequate hematologic function:

   * Absolute neutrophil count (ANC) ≥1.5 x 109/L
   * Platelet count ≥100 x 109/L
   * Hemoglobin ≥9 g/dL
4. 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
5. PT/INR \<1.5 x ULN and PTT (aPTT) \<1.5 x ULN
6. KPS ≥70.
7. Eastern Cooperative Oncology Group (ECOG) 0-1

Exclusion Criteria:

1. Prior therapies: BTK inhibitor, radiotherapy, radiotherapy in the adjuvant setting, or cytotoxic chemotherapy for primary disease of pancreatic adenocarcinoma.
2. Neuroendocrine (carcinoid, islet cell) or acinar pancreatic carcinoma
3. Known brain or leptomeningeal disease (CT or MRI scan of the brain required only in case of clinical suspicion of central nervous system involvement).
4. Major surgery within 4 weeks of first dose of study drug.
5. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
6. Treatment with a strong cytochrome P450 (CYP) 3A inhibitor.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Results at an overall median follow-up of 24.87 months
measure: Overall Survival (OS)
timeFrame: Results at an overall median follow-up of 24.87 months
Secondary outcomes:
measure: 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.
timeFrame: Results at an overall median follow-up of 24.87 months
measure: Overall Response Rate
timeFrame: Results at an overall median follow-up of 24.87 months
measure: Clinical Benefit Response
timeFrame: Results at an overall median follow-up of 24.87 months
measure: Carbohydrate Antigen 19-9 (CA19-9) Response
timeFrame: Results at an overall median follow-up of 24.87 months
measure: Patient-reported Outcome (PRO) by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).
timeFrame: Results at an overall median follow-up of 24.87 months
measure: Rate of Venous Thromboembolic Events (VTE)
timeFrame: Results at an overall median follow-up of 24.87 months
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Oncology Specialties, PC; Clearview Cancer Institute
state: Alabama
city: Avondale
country: United States
facility: Arizona Center for Cancer Care
state: Arizona
city: Daly City
country: United States
facility: St. Mary's Medical Center
state: California
city: La Jolla
country: United States
facility: Moores UCSD Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Norwich
country: United States
facility: Eastern Connecticut Hematology/Oncology Assoc.
state: Connecticut
city: Boynton Beach
country: United States
facility: Bethesda Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: Florida Hospital Tampa
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers, PC
state: Georgia
city: Harvey
country: United States
facility: Ingalls Memorial Hospital Cancer Research Center
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, LTD
state: Illinois
city: Indianapolis
country: United States
facility: Investigative Clinical Research of Indiana
state: Indiana
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Physician Group
state: Louisiana
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Pittsfield
country: United States
facility: Berkshire Hematology Oncology Services at Berkshire Medical Center Cancer and Infusion Center
state: Massachusetts
city: Chelsea
country: United States
facility: Saint Joseph Mercy Health System
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Omaha
country: United States
facility: Nebraska Medicine - Peggy D. Cowdery Patient Care Center
state: Nebraska
city: Charlotte
country: United States
facility: The Presbyterian Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Hershey
country: United States
facility: Penn State University Milton S. Hershey Medical Center
state: Pennsylvania
city: Spartanburg
country: United States
facility: Gibbs Cancer Center
state: South Carolina
city: Temple
country: United States
facility: Scott & White Memorial Hospital
state: Texas
city: Tacoma
country: United States
facility: MultiCare Health System Institute for Research and Innovation
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Hospital & Clinics
state: Washington
city: Bruxelles
country: Belgium
facility: ULB Hôpital Erasme
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Gilly
country: Belgium
facility: Grand Hôpital de Charleroi
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: C. H. U. Sart Tilman
city: Nice cedex 02
country: France
facility: Centre Antoine Lacassagne
state: Alpes Maritimes
city: Strasbourg cedex
country: France
facility: Centre Paul Strauss
state: Bas Rhin
city: Marseille cedex 5
country: France
facility: Hôpital de la Timone
state: Bouches-du-Rhône
city: Dijon cedex
country: France
facility: Centre Georges François Leclerc
state: Côte-d'Or
city: Besançon
country: France
facility: CHU Besançon - Hôpital Jean Minjoz
state: Doubs
city: Bordeaux
country: France
facility: Groupe Hospitalier Saint André - Hôpital Saint André
state: Gironde
city: Toulouse Cedex 9
country: France
facility: CHU de Toulouse - Hôpital Rangueil
state: Haute Garonne
city: Doubs
country: France
facility: Hôpital Nord Franche Comté
state: Montbeliard
city: Paris cedex 12
country: France
facility: Hôpital Saint-Antoine
state: Paris
city: Poitiers Cedex
country: France
facility: CHU Poitiers - Hôpital la Milétrie
state: Vienne
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: Baden Wuerttemberg
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
state: Baden Wuerttemberg
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe-Universitaet
state: Hessen
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
state: Nordrhein Westfalen
city: Dresden
country: Germany
facility: Gemeinschaftspraxis Haematologie und Onkologie
state: Sachsen Anhalt
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig AoeR
state: Sachsen
city: Berlin
country: Germany
facility: Onkologische Schwerpunktpraxis Kurfuerstendamm
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: Azienda Ospedaliera Ospedale Niguarda Ca' Granda
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto IRCCS
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Hwasun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: L'Hospitalet de Llobregat
country: Spain
facility: ICO l´Hospitalet - Hospital Duran i Reynals
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Specialist
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital
state: Essex
city: Manchester
country: United Kingdom
facility: The Christie
state: Greater Manchester
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre
state: Merseyside
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
state: Surrey
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Pharmacyclics LLC.
name: George Cole, MD
role: STUDY_DIRECTOR
References: