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A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT02403271
Recruitment Status : Completed
First Posted : March 31, 2015
Results First Posted : January 3, 2019
Last Update Posted : January 3, 2019
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics LLC.

Tracking Information
First Submitted Date  ICMJE February 27, 2015
First Posted Date  ICMJE March 31, 2015
Results First Submitted Date  ICMJE August 29, 2018
Results First Posted Date  ICMJE January 3, 2019
Last Update Posted Date January 3, 2019
Actual Study Start Date  ICMJE March 2015
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 7, 2018)
  • Phase 1b: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) and to Find the Recommended Phase II Dose. [ Time Frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1. ]
  • Phase 2: Efficacy of Ibrutinib in Combination With Durvalumab (MEDI4736) in Participants With Relapsed or Refractory Solid Tumors by Assessing the ORR Per RECIST 1.1. [ Time Frame: From the date of first study treatment until progressive disease per RECIST 1.1 or unacceptable toxicity. ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 25, 2015)
  • Phase 1b: Number of participants with adverse events as a measure of safety and tolerability of ibrutinib and MEDI4736 and to find the recommended Phase II dose. [ Time Frame: Up to 28 days after last subject enrolled. ]
  • Phase 2: Efficacy of ibrutinib in combination with MEDI4736 in subjects with relapsed or refractory solid tumors by assessing the ORR per RECIST 1.1. [ Time Frame: When the last subject enrolled completes at least 2 response assessments after at least 5 cycles of treatment estimated to be approximately 140 days ]
Change History Complete list of historical versions of study NCT02403271 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2018)
  • Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib [ Time Frame: 0hr, 1hr, 2hr, and 4hr post-dose ]
    Cmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1.
  • Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib [ Time Frame: 0hr, 1hr, 2hr, and 4hr post-dose ]
    AUC0-24 = the area under the plasma concentration-time curve of ibrutinib during the dosing interval on Cycle 3 Day 1
  • Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736) [ Time Frame: 60 minutes post-dose (dose administered as an infusion over a 1 hour period) ]
    Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1.
  • Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736) [ Time Frame: Pre-dose ]
    Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1
  • Phase 1b: Pharmacodynamics [ Time Frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1. ]
    BTK occupancy
  • Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) [ Time Frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1. ]
  • Phase 2: Pharmacodynamics [ Time Frame: Pre-dose ]
    BTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2015)
  • Phase 1b: Pharmacokinetics of ibrutinib. [ Time Frame: Cycle 3 Day 1 ]
    Cmax: The peak plasma concentration of ibrutinib after administration.
  • Phase 1b: Pharmacokinetics of ibrutinib. [ Time Frame: Cycle 3 Day 1 ]
    AUC0-24: The area under the plasma concentration-time curve of ibrutinib after administration form time zero to 24 hrs.
  • Phase 1b: Pharmacokinetics of MEDI4736 [ Time Frame: Cycle 6 Day 1 ]
    Cmax: The peak plasma concentration of MEDI4736 after administration.
  • Phase 1b: Pharmacokinetics of MEDI4736 [ Time Frame: Cycle 6 Day 1 ]
    Ctrough: The trough plasma concentration of MEDI4736.
  • Phase 1b: Pharmacodynamics [ Time Frame: At selected timepoints through cycle 4 estimated to be up to 112 days after initial dose. ]
    Occupancy assays for ITK and other targets in the blood.
  • Phase 2: Number of participants with adverse events as a measure of safety and tolerability of ibrutinib and MEDI4736 [ Time Frame: Up to 28 days after last subject enrolled. ]
  • Phase 2: Pharmacokinetics of ibrutinib [ Time Frame: Cycle 3 Day 1 ]
    Cmax: The peak plasma concentration of ibrutinib after administration.
  • Phase 2: Pharmacokinetics of ibrutinib [ Time Frame: Cycle 3 Day 1 ]
    AUC0-24: The area under the plasma concentration-time curve of ibrutinib after administration from zero to 24 hours.
  • Phase 2: Pharmacokinetics of MEDI4736 [ Time Frame: Cycle 6 Day 1 ]
    Cmax: The peak plasma concentration of MEDI4736 after administration.
  • Phase 2: Pharmacokinetics of MEDI4736 [ Time Frame: Cycle 6 Day 1 ]
    Ctrough: The trough plasma concentration of MEDI4736.
  • Phase 2: Pharmacodynamics [ Time Frame: At selected timepoints through cycle 4 estimated to be up to 112 days after initial dose. ]
    Occupancy assays for ITK and other targets in the blood.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors
Official Title  ICMJE A Multi-Center Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, in Combination With Durvalumab (MEDI4736), in Subjects With Relapsed or Refractory Solid Tumors
Brief Summary This is a Phase 1b/2, multi-center study to assess the safety and efficacy of ibrutinib in combination with durvalumab (MEDI4736) in participants with relapsed or refractory solid tumors.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Small Cell Lung Cancer
  • Breast Cancer
  • Pancreatic Cancer
Intervention  ICMJE
  • Drug: Ibrutinib
    BTK Inhibitor
    Other Name: PCI-32765
  • Drug: Durvalumab
    Anti PDL-1
    Other Name: MEDI4736
Study Arms  ICMJE
  • Experimental: Phase 1b
    In the Phase 1b (safety portion) of the study, a starting dose of 560 mg of ibrutinib and 10 mg/kg of MEDI4736 will be explored and will follow a 6+3 dose de-escalation design and will include a sentinel participant which will have a 3-day observation period prior to dosing of subsequent participants. Participants with one of the following three tumor types will be eligible for enrollment: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma).
    Interventions:
    • Drug: Ibrutinib
    • Drug: Durvalumab
  • Experimental: Phase 2
    Participants with one of three solid tumor types (Stage III/IV) will be enrolled in the Phase 2 portion of this protocol: NSCLC (adenocarcinoma and squamous-cell carcinoma), Breast cancer (triple-negative and HER2-positive cancer), and Pancreatic cancer (adenocarcinoma) and treated at the R2PD of ibrutinib and durvalumab determined in Phase 1b. An interim analysis will be performed to evaluate the response and the safety profile, and the study may be discontinued based on the interim efficacy and/or safety results.
    Interventions:
    • Drug: Ibrutinib
    • Drug: Durvalumab
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: September 5, 2017)
124
Original Estimated Enrollment  ICMJE
 (submitted: March 25, 2015)
160
Actual Study Completion Date  ICMJE August 2017
Actual Primary Completion Date August 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Pathologically confirmed: Non-small cell lung cancer (NSCLC, adenocarcinoma or squamous-cell carcinoma), Breast Cancer (HER2 positive or triple negative), Pancreatic Cancer (adenocarcinoma)
  2. Relapsed or refractory disease (Stage III or IV): NSCLC or pancreatic cancer must have failed at least 1 prior treatment. Breast cancer must have failed at least 2 prior treatments.
  3. Measurable lesion by RECIST 1.1
  4. Adequate hematologic function:

    • ANC >1500 cells/mm3
    • Platelet count >100,000 cells/mm3
    • HGB >9.0 g/dL
  5. Adequate hepatic and renal function:

    • AST and ALT ≤2.5 x ULN for subjects without liver metastases and ≤3.5 x ULN for subjects with liver metastases
    • Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
    • Creatinine ≤2.0 x ULN and Creatinine Clearance ≥40 mL/min (Cockcroft-Gault or 24-hour creatinine clearance collection)
  6. PT/INR <1.5 x ULN and PTT/ aPTT <1.5 x ULN

Exclusion Criteria:

  1. Mixed small cell and NSCLC histology
  2. A history of CNS involvement except as follows: Subjects with previously treated CNS metastases that are adequately treated with whole brain radiotherapy, that are neurologically stable, and do not require corticosteroids for symptomatic management for at least 14 days prior to first dose of study drug. There must be no clear evidence of radiographically active disease for at least 90 days prior to enrollment.
  3. Anti-tumor therapy within 21 days of study Day 1
  4. Prior treatment with ibrutinib or other BTK inhibitor anti-CD137 or CTLA-4 antibody. The following are exceptions to this criterion: Subjects previously treated with an anti-PD1, anti-PD-L1, or anti-PD-L2 antibody.
  5. History of allogeneic organ transplant
  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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02403271
Other Study ID Numbers  ICMJE PCYC-1135-CA
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pharmacyclics LLC.
Study Sponsor  ICMJE Pharmacyclics LLC.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Isaiah Dimery Pharmacyclics LLC.
PRS Account Pharmacyclics LLC.
Verification Date December 2018

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