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A Study of Ibrutinib as Neoadjuvant Therapy in Localized Prostate Cancer

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ClinicalTrials.gov Identifier: NCT02643667
Recruitment Status : Recruiting
First Posted : December 31, 2015
Last Update Posted : June 8, 2017
Information provided by (Responsible Party):
Lawrence Fong, University of California, San Francisco

Brief Summary:
Multicenter phase 1/2 study of neoadjuvant Ibrutinib in men with localized prostate cancer undergoing RP as their initial locally directed therapy with curative intent. To assess the immune response following neoadjuvant treatment, tissue from RP specimen will be compared to tissue from core biopsy specimen obtained prior to treatment, with each subject serving as his own control. Immune infiltration will also be compared to a reference cohort of 12 patients who had undergone RP, matched to the study population using the UCSF CAPRA-S score.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Ibrutinib Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of Ibrutinib as Neoadjuvant Therapy in Patients With Localized Prostate Cancer
Actual Study Start Date : December 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Ibrutinib
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Dose Level -1
Ibrutinib: 420 mg, orally, daily for 28 days
Drug: Ibrutinib
Experimental: Dose Level 1
Ibrutinib: 560 mg, orally, daily for 28 days
Drug: Ibrutinib
Experimental: Dose Level 2
Ibrutinib: 840 mg, orally, daily for 28 days
Drug: Ibrutinib

Primary Outcome Measures :
  1. Dose Limiting Toxicities (Phase 1) [ Time Frame: Up to 2 years ]
    CTCAE v.4.0

  2. Maximum Tolerated Dose (Phase 1) [ Time Frame: Up to 2 years ]
    CTCAE v.4.0

  3. B cell infiltration (Phase 2) [ Time Frame: Up to 2 years ]
    Immunohistochemistry (ICH)

  4. T cell infiltration (Phase 2) [ Time Frame: Up to 2 years ]
    Immunohistochemistry (ICH)

Secondary Outcome Measures :
  1. Dose-dependent change in B cell infiltration (Phase 1) [ Time Frame: Up to 2 years ]
    Immunohistochemistry (ICH)

  2. Dose-dependent change in T cell infiltration (Phase 1) [ Time Frame: Up to 2 years ]
    Immunohistochemistry (ICH)

  3. Dose-dependent change in circulating B cells (Phase 1) [ Time Frame: Up to 2 years ]
    Flow cytometry

  4. Dose-dependent change in circulating T cells (Phase 1) [ Time Frame: Up to 2 years ]
    Flow cytometry

  5. Change in frequency of circulating B cells (Phase 2) [ Time Frame: Up to 2 years ]
    Flow cytometry

  6. Change in frequency of circulating T cells (Phase 2) [ Time Frame: Up to 2 years ]
    Flow cytometry

  7. Cytotoxic effect (Phase 2) [ Time Frame: Up to 2 years ]
    Laboratory evaluations (>/= 50% PSA decline)

  8. Treatment response [ Time Frame: Up to 2 years ]
    Pathologic down-staging and/or pathologic T0

Information from the National Library of Medicine

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

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.

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

Contact: Lawrence Fong, MD 415-353-7171 Lawrence.Fong@ucsf.edu
Contact: Paula Dutton 415-885-7871 Paula.Dutton@ucsf.edu

United States, California
University of California, San Francisco Recruiting
San Francisco, California, United States, 94158
Contact: Lawrence Fong, MD    415-476-4616    lawrence.fong@ucsf.edu   
Contact: Paula Dutton, BS    415-885-7871    paula.dutton@ucsf.edu   
Sponsors and Collaborators
Lawrence Fong
Principal Investigator: Lawrence Fong, MD Uninersity of California, San Francisco

Responsible Party: Lawrence Fong, Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02643667     History of Changes
Other Study ID Numbers: 155514
First Posted: December 31, 2015    Key Record Dates
Last Update Posted: June 8, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Lawrence Fong, University of California, San Francisco:
Radical prostatectomy (RP)

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