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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02436668
Recruitment Status : Completed
First Posted : May 7, 2015
Results First Posted : November 16, 2020
Last Update Posted : November 16, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Adenocarcinoma Drug: Ibrutinib Drug: Gemcitabine Drug: Nab-paclitaxel Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 430 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Start Date : May 2015
Actual Primary Completion Date : October 2018
Actual Study Completion Date : April 25, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Ibrutinib

Ibrutinib daily in combination with:

Nab-paclitaxel and gemcitabine

Drug: Ibrutinib
Other Name: IMBRUVICA®

Drug: Gemcitabine
Drug: Nab-paclitaxel
Placebo Comparator: Placebo

Placebo daily in combination with:

Nab-paclitaxel and gemcitabine

Drug: Gemcitabine
Drug: Nab-paclitaxel



Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. Overall Response Rate [ Time Frame: Results at an overall median follow-up of 24.87 months ]
    ORR is defined as the proportion of subjects who achieve a complete response or partial response, based on investigator assessment according to RECIST 1.1.

  3. 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).


  4. 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.

  5. 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 month: TUDD1 defined as time interval between random & 1st occurrence of decrease in QLQ-C30 score ≥10 pts w/o improvement in QoL score of ≥10 points or any further available QoL data due to deterioration. Proportion of subjects with TEAE VTE of any grade defined by SMQ terms as "embolic and thrombotic events, venous". Proportion of subjects who met the "responder" criteria prior to initiation of subsequent anticancer therapy. 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 wt gain (≥7% increase from baseline maintained for ≥4 weeks) not due to fluid accumulation.

  6. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02436668


Locations
Show Show 86 study locations
Sponsors and Collaborators
Pharmacyclics LLC.
Investigators
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Study Director: George Cole, MD Pharmacyclics LLC.
  Study Documents (Full-Text)

Documents provided by Pharmacyclics LLC.:
Statistical Analysis Plan  [PDF] January 15, 2018
Study Protocol  [PDF] July 19, 2017

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Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT02436668    
Other Study ID Numbers: PCYC-1137-CA
First Posted: May 7, 2015    Key Record Dates
Results First Posted: November 16, 2020
Last Update Posted: November 16, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs