ClinicalTrials.gov
ClinicalTrials.gov Menu

Ibrutinib as Neoadjuvant Therapy in Localized Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02643667
Recruitment Status : Suspended (The study closed at UCSF and the study moved to Washington University. Waiting on IRB approval at Washington University.)
First Posted : December 31, 2015
Last Update Posted : May 28, 2018
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
30-40% of patients who undergo radical prostatetecomy (RP) with curative intent for their localized prostate cancer experience relapse of their disease. Thus, improved therapeutic approaches are needed in this patient population. Enhancing the patient's anti-tumor immune response prior to surgery may improve long-term outcomes following RP.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Ibrutinib Procedure: Blood samples for PSA and immune assays Procedure: Radical prostatectomy Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Ibrutinib as Neoadjuvant Therapy in Patients With Localized Prostate Cancer
Actual Study Start Date : July 2016
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Ibrutinib

Arm Intervention/treatment
Experimental: Phase I: Ibrutinib
  • Ibrutinib: will be given by mouth daily
  • Blood samples for PSA and for immune assays will be collected at baseline, before RP, and after RP
  • Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib
Drug: Ibrutinib
Procedure: Blood samples for PSA and immune assays
Procedure: Radical prostatectomy
-Standard of care

Experimental: Phase II: Ibrutinib
  • Ibrutinib: will be given by mouth daily
  • Blood samples for PSA and for immune assays will be collected at baseline, before RP, and after RP
  • Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib
Drug: Ibrutinib
Procedure: Blood samples for PSA and immune assays
Procedure: Radical prostatectomy
-Standard of care




Primary Outcome Measures :
  1. Dose Limiting Toxicities (Phase 1) [ Time Frame: Completion of enrollment of Phase I portion of patients ]
    • CTCAE v.4.0
    • DLTs will be defined as any of the following that are attributable to ibrutinib.

      • Any grade 4 toxicity, including hematologic toxicities with the exception of lymphocytosis. Lymphocytosis, in the absence of clinical symptoms, is excluded from DLT, as this may be considered an on-target pharmacodynamics effect of BTK inhibition.
      • Any grade 3 toxicity.
      • Any recurrence of the same grade 3 toxicity.
      • Any delay of RP due to study-drug related toxicity.
      • Any complications of RP (e.g., bleeding, delayed wound healing) deemed to be related to study drug.

  2. B cell infiltration (Phase 2) [ Time Frame: Completion of follow-up (approximately 10 weeks after start of treatment) ]
    Immunohistochemistry (ICH)

  3. T cell infiltration (Phase 2) [ Time Frame: Completion of follow-up (approximately 10 weeks after start of treatment) ]
    Immunohistochemistry (ICH)


Secondary Outcome Measures :
  1. Dose-dependent change in B cell infiltration (Phase 1) [ Time Frame: Completion of follow-up (approximately 10 weeks after start of treatment) ]
    Immunohistochemistry (ICH)

  2. Dose-dependent change in T cell infiltration (Phase 1) [ Time Frame: Completion of follow-up (approximately 10 weeks after start of treatment) ]
    Immunohistochemistry (ICH)

  3. Dose-dependent change in circulating B cells (Phase 1) [ Time Frame: Completion of follow-up (approximately 10 weeks after start of treatment) ]
    Flow cytometry

  4. Dose-dependent change in circulating T cells (Phase 1) [ Time Frame: Completion of follow-up (approximately 10 weeks after start of treatment) ]
    Flow cytometry

  5. Change in frequency of circulating B cells (Phase 2) [ Time Frame: Completion of follow-up (approximately 10 weeks after start of treatment) ]
    Flow cytometry

  6. Change in frequency of circulating T cells (Phase 2) [ Time Frame: Completion of follow-up (approximately 10 weeks after start of treatment) ]
    Flow cytometry

  7. Cytotoxic effect (Phase 2) [ Time Frame: Completion of follow-up (approximately 10 weeks after start of treatment) ]
    Laboratory evaluations (>/= 50% PSA decline)

  8. Treatment response [ Time Frame: Completion of follow-up (approximately 10 weeks after start of treatment) ]
    Pathologic down-staging and/or pathologic T0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 years of age or older
  • ECOG performance status 0 or 1
  • Histologically documented adenocarcinoma of the prostate
  • Patients must be suitable for and willing to undergo a radical prostatectomy at the completion of study therapy.
  • Adequate bone marrow function, defined as:

    • WBC >2,500 cells/mm3
    • ANC >1,500 cells/mm3
    • Hemoglobin >9 mg/dL
    • Platelet count >100,000 cells/mm3
  • Adequate renal function, defined as serum creatinine <2 mg/dL or CrCl >30 mL/min
  • Adequate liver function, defined as:

    • AST and ALT <2.5x institutional ULN
    • Serum bilirubin <1.5x institutional ULN
  • Adequate coagulation function, defined as normal PT/INR and PTT
  • Ability to understand and willingness to sign a written informed consent document
  • Available evaluable archival tumor tissue for correlative studies including assessment of immune infiltration and Btk expression is required. If archival tissue is unavailable, patients must be willing to undergo repeat prostate biopsy. Tissue is considered sufficient for correlative endpoint analyses if they are obtained from at least 2 prostate cores and consist of at least 15 unstained slides from the largest tumor volume and/or highest Gleason score. The availability of archival tissue or consent for repeat prostate biopsy is required for study eligibility; determination of tissue sufficiency is not required for study eligibility.
  • The effects of ibrutinib on the developing human fetus is unknown. Men treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of the study participation, and for 3 months after completion of treatment.

Exclusion Criteria:

  • Patients with neuroendocrine or small cell features are not eligible.
  • Any evidence of metastatic disease. Pre-operative staging will be undertaken per urologic standard of care.
  • Any prior use of hormonal therapy, including:

    • GNRH agonists or GNRH antagonists (e.g., leuprorelin, degarelix)
    • Antiandrogens (e.g., bicalutamide, flutamide, nilutamide)
    • Novel androgen-directed therapies (e.g., abiraterone, enzalutamide)
    • Any estrogen containing compounds
    • 5-alpha reductase inhibitors (e.g., finasteride, dutasteride)
    • PC-SPES or PC-x products. Other herbal therapies or supplements will be considered by the Principle Investigator on a case by case basis based on their potential for hormonal or anti-cancer therapies.
  • Prior use of immunotherapy or chemotherapy for prostate cancer
  • Prior radiation therapy for prostate cancer
  • Prior investigational therapy for prostate cancer
  • Patients may not receive any other concurrent investigational agents while on study.
  • Use of systemic steroid therapy within 28 days of study screening. Patients on inhaled or topical steroids are eligible.
  • Major surgery requiring the use of general anesthetic within 4 weeks of study enrollment
  • HIV, active hepatitis B (HBV) or active hepatitis C (HCV)

    • Patients with past HBV infection or resolved HBV infection, defined as the presence of hepatitis B core antibody (HBc Ab) and absence of hepatitis B surface antigen (HBsAg) are eligible. HBV DNA must be obtained in these patients prior to day 1 of ibrutinib therapy, but detection of HBV DNA in these patients will not exclude study participation.
    • Patients positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Inability to swallow capsules or presence of malabsorption syndromes, disease significantly affecting gastrointestinal function, history of resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete small obstruction.
  • Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Function Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to screening.
  • Uncontrolled concurrent illness, or any underlying medical condition, which in the Principal Investigator's opinion will make the administration of ibrutinib hazardous or obscure the interpretation of adverse events.
  • Concurrent active malignancy other than non-melanoma skin cancers. Patients are considered to be free of active malignancy if they have completed curative therapy and have a <30% risk of relapse.
  • Moderate or severe hepatic impairment defined as Child-Pugh Class B or C.
  • History of congenital bleeding diathesis.
  • Concomitant use of anticoagulants including warfarin, other Vitamin K antagonists, and enoxaparin.
  • Patients who require treatment with a strong cytochrome P450 (CYP) 3A inhibitor.
  • Vaccination with live, attenuated vaccines within 4 weeks of first dose of study drug.
  • Major surgery within 4 weeks of the first dose of study drug.
  • Patients on anti-platelet agents including clopidogrel and glycoprotein IIb/IIIa inhibitors. Aspirin is allowed, but should be held before surgery according to standard practices.
  • Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child-Pugh classification

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): NCT02643667


Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94158
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Russell K Pachynski, M.D. Washington University School of Medicine

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02643667     History of Changes
Other Study ID Numbers: 18-x143
First Posted: December 31, 2015    Key Record Dates
Last Update Posted: May 28, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Washington University School of Medicine:
Radical prostatectomy (RP)

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases