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Prostate CancerPhase 2NCT02643667

Ibrutinib as Neoadjuvant Therapy in Localized Prostate Cancer

A Phase 2 study testing Ibrutinib and Radical prostatectomy in people with Prostate Cancer, run by Washington University School of Medicine at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Ibrutinib and Radical prostatectomy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
2 sitesUnited States
Study dates
Jul 2016to 12 Apr 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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)
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  • 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.
  • Chemotherapy ≤ 21 days prior to first administration of study treatment and/or monoclonal antibody ≤ 6 weeks prior to first administration of study treatment
  • Prior radiation therapy for prostate cancer
  • Prior exposure to BTK inhibitors
  • 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.
  • Concurrent systemic immunosuppressive therapy within 21 days of the first dose of study drug.
  • 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.
  • Recent infection requiring systemic treatment that was completed within 14 days prior to the first dose of study drug
  • 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.
  • History of congenital bleeding diathesis.
  • Known bleeding disorders (e.g. von Willebrand's disease or hemophilia).
  • Concomitant use of anticoagulants including warfarin, other Vitamin K antagonists, and enoxaparin.
  • Subjects who received a strong or moderate cytochrome P450 (CYP) 3A4 inhibitor within 7 days prior to the first dose of ibrutinib or patients who require treatment with a strong or moderate cytochrome P450 (CYP) 3A inhibitor.
  • Vaccination with live, attenuated vaccines within 4 weeks of 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
  • Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
  • Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to CTCAE v 4.03 grade 0 or 1 or to the levels dictated in the eligibility criteria with the exception of alopecia.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of California, San Francisco

    San Francisco, California, 94158

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase 2 Study of Ibrutinib as Neoadjuvant Therapy in Patients With Localized Prostate Cancer

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

Conditions
Prostate Cancer
Being tested
Ibrutinib, Radical prostatectomy
Keywords
Radical prostatectomy (RP)
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IbrutinibDrug

    -Ibrutinib will be supplied by Pharmacyclics Inc.

  • Radical prostatectomyProcedure or surgery

    -Standard of care

Study groups in NCT02643667
Study groupRoleWhat they receive
Phase I: IbrutinibExperimental* Ibrutinib 840 mg by mouth once daily for 2 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib.
Receives: Drug: Ibrutinib; Procedure: Radical prostatectomy
Safety Run-In and Phase II: IbrutinibExperimental* Ibrutinib 840 mg by mouth once daily for 4 weeks. * Radical prostatectomy will be performed at least 7 days but not more than 12 days following the last scheduled dose of ibrutinib
Receives: Drug: Ibrutinib; Procedure: Radical prostatectomy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose Limiting Toxicities (Phase I and Safety Run-In)

    • 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.

    Measured: Completion of DLT follow-up (2 weeks for Phase I portion and 28 days for Safety Run-In)

  2. Percentage of Participants With Positive Responses - CD20+ B Cells, IL-10+ B Cells, CD3+ T Cells, CD8+ Cytotoxic T Cells, Effector CD4+FOXP3- T Cells, and CD4+FOX3+ T Regulatory Cells

    In pre-treatment biopsy, RP tissue, and reference RP tissue quantitated by immunohistochemistry (IHC). Patients will be considered to have a positive response if there is >2 fold decrease from pre-treatment to post-treatment, or considered to have a negative response if there is <2 fold decrease. The percentage of participants who have "positive" responses are represented in the outcome measure data.

    Measured: Pre-treatment and at time of RP (approximately 10 weeks after start of treatment)

  3. Mean B Cell Fold Change of CD20+ B Cells

    Participants will be considered to have a positive response if there is >2 fold decrease (0.5 or less B cell fold change) or considered to have a negative response if there is <2 fold decrease. Descriptive statistics will be used to describe pre-treatment biopsy immune infiltration, post-treatment RP immune infiltration, and immune infiltration of reference RP tissue.

    Measured: At RP (approximately 10 weeks after start of treatment)

Secondary outcomes (3)

  1. Percentage of Participants With Positive Responses - CD19+ B Cells, CD25^highCD27^highCD86^High B Regulatory Cells, and CD3+, CD8+, CD4+FOXP3- and CD4+FOXP3+ T Cells Induced by Neoadjuvant Ibrutinib in Patients by Flow Cytometry

    Patients will be considered to have a positive response if there is >2 fold decrease from pre-treatment to post-treatment, or considered to have a negative response if there is <2 fold decrease. The percentage of partcipants who have "positive" responses are represented in the outcome measure data.

    Measured: Pre-treatment to RP (approximately 10 weeks after start of treatment)

  2. Number of Participants Who Had a 50% or Greater Decline in PSA

    Measured: At baseline and approximately day 29

  3. Number of Participants With a Treatment Response (Safety Lead-In and Phase II Only)

    Pathologic down-staging and/or pathologic T0

    Measured: Completion of follow-up (approximately 10 weeks after start of treatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Dec 2015 (estimated)
  2. Study startJul 2016
  3. Primary completion12 Apr 2023
  4. Study completion12 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02643667
Sponsor's protocol ID
201808057
Status last verified
Dec 2024
First submitted
28 Dec 2015
Last updated
8 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib and Radical prostatectomy in people with Prostate Cancer, run by Washington University School of Medicine at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (Phase I and Safety Run-In) (time frame: Completion of DLT follow-up (2 weeks for Phase I portion and 28 days for Safety Run-In)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02643667.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2025.

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