Daratumumab or FMS Inhibitor JNJ-40346527 Before Surgery in Treating Patients With High-Risk, Resectable Localized or Locally Advanced Prostate Cancer

NCT03177460 | Completed Phase 1 FDA Drug

• 3 other identifiers: 2017-0103NCI-2018-01179P30CA016672
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects of daratumumab or FMS inhibitor JNJ-40346527 before surgery in treating patients with high-risk prostate cancer that can be removed by surgery and has not spread to other parts of the body or has spread to nearby tissue or lymph nodes. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spreadFMS inhibitor JNJ-40346527 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving daratumumab or FMS inhibitor JNJ-40346527 before surgery may work better in treating patients with prostate cancer.

Conditions

Prostate Adenocarcinoma; Stage III Prostate Cancer AJCC v8; Stage IIIA Prostate Cancer AJCC v8; Stage IIIB Prostate Cancer AJCC v8; Stage IIIC Prostate Cancer AJCC v8; Testosterone Greater Than 150 ng/dL

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events

  Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Will be recorded for all patients, recording name, grade, start and end dates, attribution to study drug, and whether the event was alleviated or controlled with relevant appropriate care similar to Phase I trials.

  Up to week 18

Secondary Outcomes (3)

• Pathological complete response (CR)

  Up to week 18

• Immune changes in blood

  Baseline up to week 18

• Immune changes in tumor tissue

  Baseline up to week 18

Study Arms (2)

Arm A (daratumumab)

EXPERIMENTAL

Patients receive daratumumab IV over 4-8 hours once weekly for 4 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy during week 6.

Biological: Daratumumab; Procedure: Radical Prostatectomy

Arm B (FMS inhibitor JNJ-40346527)

EXPERIMENTAL

Patients receive FMS inhibitor JNJ-40346527 PO BID for 4-5 weeks in the absence of disease progression or unacceptable toxicity. After a 3 day wash-out period, patients undergo radical prostatectomy.

Drug: FMS Inhibitor JNJ-40346527; Procedure: Radical Prostatectomy

Interventions

Daratumumab BIOLOGICAL

Given IV

Also known as: Anti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414

Arm A (daratumumab)

FMS Inhibitor JNJ-40346527 DRUG

Given PO

Also known as: JNJ-40346527

Arm B (FMS inhibitor JNJ-40346527)

Radical Prostatectomy PROCEDURE

Undergo radical prostatectomy

Also known as: Prostatovesiculectomy

Arm A (daratumumab); Arm B (FMS inhibitor JNJ-40346527)

Eligibility Criteria

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

You may qualify if:

• Consent to MD Anderson laboratory protocol PA13-0291.
• Histological documentation of adenocarcinoma of the prostate reviewed at MD Anderson Cancer Center. Patients with small cell, neuroendocrine, or transitional cell carcinomas are not eligible.
• Patients with high-risk prostate cancer (at least 1 core with Gleason sum \>= 8) must have at least three core biopsies involved with cancer (a minimum of 6 core biopsies, must be obtained at baseline). A prostate biopsy within 3 months from screening is allowed for entry requirements.
• No evidence of metastatic disease as documented by technetium-99m (99mTc) bone scan and by computed tomography (CT) or magnetic resonance imaging (MRI) scans.
• Eugonadal state (serum testosterone \> 150 ng/dL).
• Localized or locally advanced disease deemed by the surgeon to be resectable. Patients must be appropriate candidates for radical prostatectomy plus pelvic lymph node dissection.
• No prior treatment for prostate cancer including prior surgery (excluding transurethral resection of the prostate \[TURP\]), cryoablation, pelvic lymph node dissection, radiation therapy, hormonal therapy or chemotherapy.
• To avoid risk of drug exposure through the ejaculate (even men with vasectomies), subjects must use a condom during sexual activity while on study drug and for 3 months following the last dose of study drug. If the subject is engaged in sexual activity with a woman of childbearing potential, a condom is required along with another effective contraceptive method consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies and their partners. Donation of sperm is not allowed while on study drug and for 3 months following the last dose of study drug.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade of 0 or 1.
• AT SCREENING: Hemoglobin within institutional normal limits. Administration of growth factors or blood transfusions will not be allowed to confirm eligibility.
• AT SCREENING: Platelet count within institutional normal limits. Administration of growth factors or blood transfusions will not be allowed to confirm eligibility.
• AT SCREENING: Absolute neutrophil count within institutional normal limits. Administration of growth factors or blood transfusions will not be allowed to confirm eligibility.
• AT SCREENING: Absolute lymphocyte count within institutional normal limits. Administration of growth factors or blood transfusions will not be allowed to confirm eligibility.
• AT SCREENING: Serum chemistries, renal and liver panels within institutional normal limits or meets the requirements for radical prostatectomy.
• Each subject must sign an informed consent form (ICF) indicating that he understands the purpose of and procedures required for the study and is willing to participate in the study.

You may not qualify if:

• Prior hormone therapy for prostate cancer including orchiectomy, antiandrogens, ketoconazole, or estrogens (5-alpha reductase inhibitors allowed), or luteinizing hormone-releasing hormone (LHRH) agonists/antagonists.
• Currently enrolled in another interventional study.
• Concurrent treatment with systemic corticosteroids (prednisone dose \> 10 mg per day or equivalent) or other immunosuppressive drugs \< 14 days prior to treatment initiation. Steroids that are topical, inhaled, nasal (spray), or ophthalmic solution are permitted.
• History of or known or suspected autoimmune disease (exception\[s\]: subjects with vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism that is clinically euthyroid at screening are allowed).
• Known evidence of an active infection requiring systemic therapy such as human immunodeficiency virus (HIV), active hepatitis, or fungal infection.
• History of clinically significant cardiovascular disease including, but not limited to:
• Myocardial infarction or unstable angina =\< 6 months prior to treatment initiation.
• Clinically significant cardiac arrhythmia.
• Deep vein thrombosis, pulmonary embolism, stroke =\< 6 months prior to treatment initiation.
• Congestive heart failure (New York Heart Association class III-IV).
• Pericarditis/clinically significant pericardial effusion.
• Myocarditis.
• Endocarditis.
• History of major implant(s) or device(s), including but not limited to:
• Prosthetic heart valve(s).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

daratumumab; JNJ-40346527

Condition Hierarchy (Ancestors)

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

Study Officials

• Sumit K Subudhi

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 6, 2017
• Study Start: June 7, 2017
• Primary Completion: January 30, 2024
• Study Completion: January 30, 2024
• Last Updated: May 3, 2024

Record last verified: 2024-05

Locations

US (1)