Study of Ibrutinib vs Placebo, in Combination With Nab-paclitaxel and Gemcitabine, in the First Line Treatment of Patients With Metastatic Pancreatic Adenocarcinoma (RESOLVE)

Metastatic Pancreatic Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02436668
• Other study ID #: PCYC-1137-CA
• Status: Completed
• Phase: Phase 3
• Start date: May 2015
• Est. completion date: April 25, 2019

Study information

• Verified date: December 2020
• Source: Pharmacyclics LLC.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 430
• Est. completion date: April 25, 2019
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Metastatic Pancreatic Adenocarcinoma

Intervention

Drug:
• Ibrutinib

• Gemcitabine

• Nab-paclitaxel

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Pharmacyclics LLC.

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Korea, Republic of,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	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.	Results at an overall median follow-up of 24.87 months
Primary	Overall Survival (OS)	OS, is defined as the time from date of randomization until date of death from any cause.	Results at an overall median follow-up of 24.87 months
Secondary	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.	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.	Results at an overall median follow-up of 24.87 months
Secondary	Overall Response Rate	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.	Results at an overall median follow-up of 24.87 months
Secondary	Clinical Benefit Response	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).	Results at an overall median follow-up of 24.87 months
Secondary	Carbohydrate Antigen 19-9 (CA19-9) Response	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.	Results at an overall median follow-up of 24.87 months
Secondary	Patient-reported Outcome (PRO) by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).	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.	Results at an overall median follow-up of 24.87 months
Secondary	Rate of Venous Thromboembolic Events (VTE)	The VTE rate is defined as percentage of subjects with Venous thromboembolic events (SMQ) per investigator assessment.	Results at an overall median follow-up of 24.87 months