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

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ClinicalTrials.gov Identifier: NCT02436668
Recruitment Status : Completed
First Posted : May 7, 2015
Results First Posted : November 16, 2020
Last Update Posted : December 30, 2020
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics LLC.

Tracking Information
First Submitted Date  ICMJE May 4, 2015
First Posted Date  ICMJE May 7, 2015
Results First Submitted Date  ICMJE October 31, 2019
Results First Posted Date  ICMJE November 16, 2020
Last Update Posted Date December 30, 2020
Study Start Date  ICMJE May 2015
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2020)
  • Progression Free Survival (PFS) [ Time Frame: 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) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 6, 2015)
Progression Free Survival (PFS) [ Time Frame: Approximately 3 years after the first subject is randomized. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2020)
  • 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. [ Time Frame: 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.
  • Overall Response Rate [ Time Frame: 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.
  • Clinical Benefit Response [ Time Frame: 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).
  • Carbohydrate Antigen 19-9 (CA19-9) Response [ Time Frame: 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.
  • Patient-reported Outcome (PRO) by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). [ Time Frame: 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.
  • Rate of Venous Thromboembolic Events (VTE) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2015)
  • 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. [ Time Frame: Up tp 30 days after the last participating subject discontinues study drug ]
  • Overall Survival (OS) [ Time Frame: Three years after first subject enrolled ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Pancreatic Adenocarcinoma
Intervention  ICMJE
  • Drug: Ibrutinib
    Other Name: IMBRUVICA®
  • Drug: Gemcitabine
  • Drug: Nab-paclitaxel
Study Arms  ICMJE
  • Active Comparator: Ibrutinib

    Ibrutinib daily in combination with:

    Nab-paclitaxel and gemcitabine

    Interventions:
    • Drug: Ibrutinib
    • Drug: Gemcitabine
    • Drug: Nab-paclitaxel
  • Placebo Comparator: Placebo

    Placebo daily in combination with:

    Nab-paclitaxel and gemcitabine

    Interventions:
    • Drug: Gemcitabine
    • Drug: Nab-paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 11, 2018)
430
Original Estimated Enrollment  ICMJE
 (submitted: May 6, 2015)
326
Actual Study Completion Date  ICMJE April 25, 2019
Actual Primary Completion Date October 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Italy,   Korea, Republic of,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02436668
Other Study ID Numbers  ICMJE PCYC-1137-CA
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pharmacyclics LLC.
Study Sponsor  ICMJE Pharmacyclics LLC.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: George Cole, MD Pharmacyclics LLC.
PRS Account Pharmacyclics LLC.
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP