Ibrutinib as Neoadjuvant Therapy in Localized Prostate Cancer

NCT02643667 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 201808057
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

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

Conditions

Prostate Cancer

Keywords

Radical prostatectomy (RP)

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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.

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

• 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.

  At RP (approximately 10 weeks after start of treatment)

Secondary Outcomes (3)

• 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

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

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

  At baseline and approximately day 29

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

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

Study Arms (2)

Phase I: Ibrutinib

EXPERIMENTAL

* 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.

Drug: Ibrutinib; Procedure: Radical prostatectomy

Safety Run-In and Phase II: Ibrutinib

EXPERIMENTAL

* 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

Drug: Ibrutinib; Procedure: Radical prostatectomy

Interventions

Ibrutinib DRUG

-Ibrutinib will be supplied by Pharmacyclics Inc.

Phase I: Ibrutinib; Safety Run-In and Phase II: Ibrutinib

Radical prostatectomy PROCEDURE

-Standard of care

Phase I: Ibrutinib; Safety Run-In and Phase II: Ibrutinib

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Pharmacyclics LLC.: collaborator

Study Sites (2)

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

ibrutinib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Dr. Russell K. Pachynski
• Organization: Washington University School of Medicine

rkpachynski@wustl.edu

314-286-2341

Study Officials

• Russell K Pachynski, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2015
• First Posted: December 31, 2015
• Study Start: July 1, 2016
• Primary Completion: April 12, 2023
• Study Completion: April 12, 2023
• Last Updated: January 8, 2025
• Results First Posted: January 8, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)