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Clinical Trial Record

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

2015-03

2017-08

2017-08

124

Study Overview

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

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.

N/A

  • Non-Small Cell Lung Cancer
  • Breast Cancer
  • Pancreatic Cancer
  • DRUG: Ibrutinib
  • DRUG: Durvalumab
  • PCYC-1135-CA

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates Results Reporting Dates Study Record Updates

2015-02-27  

2018-08-29  

2018-12-07  

2015-03-25  

2018-12-07  

2019-01-03  

2015-03-31  

2019-01-03  

2018-12  

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/ArmIntervention/Treatment
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 per

DRUG: Ibrutinib

  • BTK Inhibitor

DRUG: Durvalumab

  • Anti PDL-1
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 (

DRUG: Ibrutinib

  • BTK Inhibitor

DRUG: Durvalumab

  • Anti PDL-1
Primary Outcome MeasuresMeasure DescriptionTime Frame
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.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.From the date of first study treatment until progressive disease per RECIST 1.1 or unacceptable toxicity.
Secondary Outcome MeasuresMeasure DescriptionTime Frame
Phase 1b/2: Pharmacokinetics (Cmax) of IbrutinibCmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1.0hr, 1hr, 2hr, and 4hr post-dose
Phase 1b/2: Pharmacokinetics (AUC0-24h) of IbrutinibAUC0-24 = the area under the plasma concentration-time curve of ibrutinib during the dosing interval on Cycle 3 Day 10hr, 1hr, 2hr, and 4hr post-dose
Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1.60 minutes post-dose (dose administered as an infusion over a 1 hour period)
Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1Pre-dose
Phase 1b: PharmacodynamicsBTK occupancyFrom the date of first study treatment until DLT or disease progression per RECIST 1.1.
Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Phase 2: PharmacodynamicsBTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1.Pre-dose

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

    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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

    • STUDY_DIRECTOR: Isaiah Dimery, Pharmacyclics LLC.

    Publications

    The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

    General Publications

    No publications available

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