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Trial record 71 of 307 for:    IBRUTINIB

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.

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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Breast Cancer Pancreatic Cancer Drug: Ibrutinib Drug: Durvalumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 124 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 2015
Actual Primary Completion Date : August 2017
Actual Study Completion Date : August 2017

Resource links provided by the National Library of Medicine


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 Name: PCI-32765

Drug: Durvalumab
Anti PDL-1
Other Name: 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 Name: PCI-32765

Drug: Durvalumab
Anti PDL-1
Other Name: MEDI4736




Primary Outcome Measures :
  1. 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. ]
  2. 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. ]

Secondary Outcome Measures :
  1. 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.

  2. 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

  3. 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.

  4. 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

  5. Phase 1b: Pharmacodynamics [ Time Frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1. ]
    BTK occupancy

  6. 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. ]
  7. 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.



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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. 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

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): NCT02403271


Locations
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United States, Alabama
Birmingham, Alabama, United States, 35294
United States, Arizona
Scottsdale, Arizona, United States, 85258
United States, California
La Jolla, California, United States, 92093
Los Angeles, California, United States, 90025
Los Angeles, California, United States, 90048
Palo Alto, California, United States, 94305
San Francisco, California, United States, 94115
United States, Florida
Gainesville, Florida, United States, 32610
Orlando, Florida, United States, 32806
United States, Illinois
Chicago, Illinois, United States, 60637
Peoria, Illinois, United States, 61615
United States, New Jersey
Hackensack, New Jersey, United States, 07601
United States, North Carolina
Durham, North Carolina, United States, 27710
United States, Tennessee
Germantown, Tennessee, United States, 38120
Nashville, Tennessee, United States, 37212
United States, Texas
Houston, Texas, United States, 77030
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Pharmacyclics LLC.
Investigators
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Study Director: Isaiah Dimery Pharmacyclics LLC.
  Study Documents (Full-Text)

Documents provided by Pharmacyclics LLC.:
Statistical Analysis Plan  [PDF] December 1, 2017
Study Protocol  [PDF] December 18, 2015


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Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT02403271     History of Changes
Other Study ID Numbers: PCYC-1135-CA
First Posted: March 31, 2015    Key Record Dates
Results First Posted: January 3, 2019
Last Update Posted: January 3, 2019
Last Verified: December 2018

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

Additional relevant MeSH terms:
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Breast Neoplasms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Pancreatic Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Durvalumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs