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

December 7, 2018 updated by: Pharmacyclics LLC.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

124

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
    • Arizona
      • Scottsdale, Arizona, United States, 85258
    • California
      • La Jolla, California, United States, 92093
      • Los Angeles, California, United States, 90048
      • Los Angeles, California, United States, 90025
      • Palo Alto, California, United States, 94305
      • San Francisco, California, United States, 94115
    • Florida
      • Gainesville, Florida, United States, 32610
      • Orlando, Florida, United States, 32806
    • Illinois
      • Chicago, Illinois, United States, 60637
      • Peoria, Illinois, United States, 61615
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
    • North Carolina
      • Durham, North Carolina, United States, 27710
    • Tennessee
      • Germantown, Tennessee, United States, 38120
      • Nashville, Tennessee, United States, 37212
    • Texas
      • Houston, Texas, United States, 77030
      • San Antonio, Texas, United States, 78229

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / 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 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).
Drug: Ibrutinib
BTK Inhibitor
Other Names:
  • PCI-32765
Drug: Durvalumab
Anti PDL-1
Other Names:
  • MEDI4736
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.
Drug: Ibrutinib
BTK Inhibitor
Other Names:
  • PCI-32765
Drug: Durvalumab
Anti PDL-1
Other Names:
  • MEDI4736

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time 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.
Time Frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
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.
From the date of first study treatment until progressive disease per RECIST 1.1 or unacceptable toxicity.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
0hr, 1hr, 2hr, and 4hr post-dose
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
0hr, 1hr, 2hr, and 4hr post-dose
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.
60 minutes post-dose (dose administered as an infusion over a 1 hour period)
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
Pre-dose
Phase 1b: Pharmacodynamics
Time Frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
BTK occupancy
From 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)
Time Frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
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.
Pre-dose

Collaborators and Investigators

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

Sponsor

Pharmacyclics LLC.

Investigators

  • Study Director: Isaiah Dimery, Pharmacyclics LLC.

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 Major Dates

Study Start (Actual)

March 1, 2015

Primary Completion (Actual)

August 1, 2017

Study Completion (Actual)

August 1, 2017

Study Registration Dates

First Submitted

February 27, 2015

First Submitted That Met QC Criteria

March 25, 2015

First Posted (Estimate)

March 31, 2015

Study Record Updates

Last Update Posted (Actual)

January 3, 2019

Last Update Submitted That Met QC Criteria

December 7, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCYC-1135-CA

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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