Clinical Trials /

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

NCT03177460

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Daratumumab or FMS Inhibitor JNJ-40346527 Before Surgery in Treating Patients With High-Risk, Resectable Localized or Locally Advanced Prostate Cancer
  • Official Title: A Pilot Presurgical Study of Daratumumab (CD38 Antagonist) or JNJ-40346527 in Men With High-Risk Localized Prostate Cancer Followed by Radical Prostatectomy

Clinical Trial IDs

  • ORG STUDY ID: 2017-0103
  • SECONDARY ID: NCI-2018-01179
  • SECONDARY ID: 2017-0103
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03177460

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

Interventions

DrugSynonymsArms
DaratumumabAnti-CD38 Monoclonal Antibody, Darzalex, HuMax-CD38, JNJ-54767414Arm A (daratumumab)
FMS Inhibitor JNJ-40346527JNJ-40346527Arm B (FMS inhibitor JNJ-40346527)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. Safety and tolerability of therapy with the study drugs in men with high-risk localized
      prostate cancer.

      SECONDARY OBJECTIVES:

      I. To assess the proportion of patients who achieve pathological complete response (CR) with
      the study drugs in men with high-risk localized prostate cancer.

      EXPLORATORY OBJECTIVES:

      I. To study immunological changes in tumor tissues and peripheral blood in response to the
      study drugs in men with high-risk localized prostate cancer.

      OUTLINE: Patients are assigned to 1 of 2 arms.

      ARM A: Patients receive daratumumab intravenously (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.

      ARM B: Patients receive FMS inhibitor JNJ-40346527 orally (PO) twice daily (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.

      After completion of study treatment, patients are followed up at week 18.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (daratumumab)ExperimentalPatients 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.
  • Daratumumab
Arm B (FMS inhibitor JNJ-40346527)ExperimentalPatients 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.
  • FMS Inhibitor JNJ-40346527

Eligibility Criteria

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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).

               -  Artificial joints and prosthetics placed =< 12 months prior to treatment
                  initiation.

               -  Current or prior history of infection or other clinically significant adverse
                  event associated with an exogenous implant or device that cannot be removed.

          -  Other prior malignancy (exceptions: adequately treated basal cell or squamous cell
             skin cancer, superficial bladder cancer, or any other cancer in situ currently in
             complete remission) =< 2 years prior to enrollment.

          -  Any medical, psychological or social condition that in the opinion of the
             investigator, would preclude participation in this study.

          -  DARATUMUMAB ONLY: Seropositive for hepatitis B (defined by a positive test for
             hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects
             who are HBsAg negative but positive for antibodies to hepatitis B core antigen
             [antiHBc] and/or antibodies to hepatitis B surface antigen [antiHBs]) must be screened
             using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV)
             DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with
             serologic findings suggestive of HBV vaccination (antiHBs positivity as the only
             serologic marker) AND a known history of prior HBV vaccination, do not need to be
             tested for HBV deoxyribonucleic acid (DNA) by PCR. Seropositive for hepatitis C
             (except in the setting of a sustained virologic response [SVR], defined as aviremia at
             least 12 weeks after completion of antiviral therapy)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to week 18
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Pathological complete response (CR)
Time Frame:Up to week 18
Safety Issue:
Description:Pathologic response will be measured from the surgical specimen. Pathologic CR is defined as the absence of residual tumor in the radical prostatectomy specimen (i.e., pT0).
Measure:Immune changes in blood
Time Frame:Baseline up to week 18
Safety Issue:
Description:
Measure:Immune changes in tumor tissue
Time Frame:Baseline up to week 18
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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