Clinical Trials /

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

NCT02403271

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Solid Tumors
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: PCYC-1135-CA
  • NCT ID: NCT02403271

Conditions

  • Non-Small Cell Lung Cancer
  • Breast Cancer
  • Pancreatic Cancer

Interventions

DrugSynonymsArms
IbrutinibPCI-32765Phase 1b/2
Durvalumab (MEDI4736)Phase 1b/2

Purpose

This is a Phase 1b/2, multi-center study to assess the safety and efficacy of ibrutinib in combination with durvalumab (MEDI4736) in subjects with relapsed or refractory solid tumors.

Trial Arms

NameTypeDescriptionInterventions
Phase 1b/2ExperimentalPhase 1b: Subjects will receive ibrutinib daily in combination with Durvalumab (MEDI4736) IV at various dose levels to determine the Recommended Phase II dose level. Phase 2: Subjects will receive ibrutinib daily in combination with Durvalumab (MEDI4736) IV at the Recommended Phase II dose level.
  • Ibrutinib
  • Durvalumab (MEDI4736)

Eligibility Criteria

        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 or Creatinine Clearance ≥40 mL/min

          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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Phase 1b: Pharmacokinetics of ibrutinib.
Time Frame:Cycle 3 Day 1
Safety Issue:
Description:Cmax: The peak plasma concentration of ibrutinib after administration.
Measure:Phase 1b: Pharmacokinetics of ibrutinib.
Time Frame:Cycle 3 Day 1
Safety Issue:
Description:AUC0-24: The area under the plasma concentration-time curve of ibrutinib after administration form time zero to 24 hrs.
Measure:Phase 1b: Pharmacokinetics of MEDI4736
Time Frame:Cycle 6 Day 1
Safety Issue:
Description:Cmax: The peak plasma concentration of MEDI4736 after administration.
Measure:Phase 1b: Pharmacokinetics of MEDI4736
Time Frame:Cycle 6 Day 1
Safety Issue:
Description:Ctrough: The trough plasma concentration of MEDI4736.
Measure:Phase 1b: Pharmacodynamics
Time Frame:At selected timepoints through cycle 4 estimated to be up to 112 days after initial dose.
Safety Issue:
Description:Occupancy assays for ITK and other targets in the blood.
Measure: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.
Safety Issue:
Description:
Measure:Phase 2: Pharmacokinetics of ibrutinib
Time Frame:Cycle 3 Day 1
Safety Issue:
Description:Cmax: The peak plasma concentration of ibrutinib after administration.
Measure:Phase 2: Pharmacokinetics of ibrutinib
Time Frame:Cycle 3 Day 1
Safety Issue:
Description:AUC0-24: The area under the plasma concentration-time curve of ibrutinib after administration from zero to 24 hours.
Measure:Phase 2: Pharmacokinetics of MEDI4736
Time Frame:Cycle 6 Day 1
Safety Issue:
Description:Cmax: The peak plasma concentration of MEDI4736 after administration.
Measure:Phase 2: Pharmacokinetics of MEDI4736
Time Frame:Cycle 6 Day 1
Safety Issue:
Description:Ctrough: The trough plasma concentration of MEDI4736.
Measure:Phase 2: Pharmacodynamics
Time Frame:At selected timepoints through cycle 4 estimated to be up to 112 days after initial dose.
Safety Issue:
Description:Occupancy assays for ITK and other targets in the blood.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Pharmacyclics LLC.

Trial Keywords

  • Pharmacyclics
  • PCYC
  • Ibrutinib
  • Durvalumab (MEDI4736)
  • Relapsed Refractory Solid Tumor
  • Non-Small Cell Lung Cancer
  • NSCLC
  • Squamous
  • Squamous NSCLC
  • Squamous Non-Small Cell Lung Cancer
  • Immunotherapy
  • IMBRUVICA®
  • Tumor Immunotherapy
  • Anti-PD-L1
  • Lung Cancer
  • Breast Cancer
  • Triple Negative
  • HER2 Positive
  • HER2 + Breast Cancer
  • Pancreatic Cancer

Last Updated

September 5, 2017