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Safety & Immunogenicity of JNJ-64041809, a Live Attenuated Double-deleted Listeria Immunotherapy, in Participants With Metastatic Castration-resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT02625857
Recruitment Status : Active, not recruiting
First Posted : December 9, 2015
Last Update Posted : March 1, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to find and evaluate the recommended Phase 2 dose (RP2D) of JNJ-64041809, a live attenuated double deleted (LADD) Listeria monocytogenes (bacteria in which two virulence genes, which encode molecules that help cause disease, have been removed) when administered intravenously to participants with metastatic castration-resistant prostate cancer (mCRPC).

Condition or disease Intervention/treatment Phase
Prostatic Neoplasms, Castration-Resistant Biological: JNJ-64041809 (Cohort 1A and 1B) Biological: JNJ-64041809 (Cohort 2A and 2B) Phase 1

Detailed Description:
This is a first-in-human (FIH), Phase 1, open-label, multicenter and 2-part study. The Part 1 of study will be Dose Escalation phase to determine the recommended Phase 2 dose (RP2D) based on safety and pharmacodynamic assessments and Part 2 will be Dose Expansion Phase to evaluate 2 expansion cohorts (Cohort 2A and 2B) after the RP2D for JNJ-64041809 is determined in Part 1. The study will consist of a Screening Period (from signing of informed consent until immediately before the first dose), an open-label Treatment Period (from the first dose of study drug until the End-of-Treatment Visit); and a Post treatment Follow-up Period (after the End-of Treatment Visit until study discontinuation). Participants will be primarily evaluated for RP2D. Participants safety will be evaluated throughout the study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 1 Study of the Safety and Immunogenicity of JNJ-64041809, a Live Attenuated Listeria Monocytogenes Immunotherapy, in Subjects With Metastatic Castration-resistant Prostate Cancer
Actual Study Start Date : December 10, 2015
Actual Primary Completion Date : July 7, 2017
Estimated Study Completion Date : June 15, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Dose Cohort 1A and 1B
JNJ-64041809 will be administered intravenously (IV) once every 21 days.
Biological: JNJ-64041809 (Cohort 1A and 1B)
JNJ-64041809 will be administered IV at a lower dose in Cohort 1A (1x10^8 colony forming units [CFU]) and at a higher dose in Cohort 1B (1x10^9 CFU).
Experimental: Dose Cohort 2A and 2B
JNJ-64041809 will be administered intravenously (IV) once every 21 days.
Biological: JNJ-64041809 (Cohort 2A and 2B)
JNJ-64041809 will be administered intravenously (IV) once every 21 days at the recommended dose as determined in Cohort 1A or 1B.



Primary Outcome Measures :
  1. Part 1: Incidence of Dose-limiting-toxicity (DLT) [ Time Frame: first 21 days after the first infusion ]
    Percentage of Participants who Experienced DLT will be evaluated. The DLT dose level is defined as an unacceptable level of toxicity as evidenced by a DLT rate of greater than or equal to (>=) 33 percent (%).

  2. Part 2: Antigen-specific T-cell Response [ Time Frame: up to 1 year ]
    Biomarker studies will be performed to evaluate immune responses to the vaccine after the first intravenous (IV) immunization.

  3. Part 1 and Part 2: Incidence of Adverse Events (AEs) [ Time Frame: From signing of informed consent form to 30 days after last dose of study drug ]
    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Incidence was defined as the number of participants who experienced an adverse event within their period of participation in this study. Incidence of adverse events will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE).


Secondary Outcome Measures :
  1. Part 1 and Part 2: Objective Response Rate (ORR) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
    Objective response rate is defined as the percentage of participants who achieve complete response (CR) or partial response (PR), as assessed by the investigator.

  2. Part 1 and Part 2: Duration of Response (DOR) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
    Duration of response will be calculated from the date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death.

  3. Part 1 and Part 2: Progression-free Survival (PFS) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
    Progression-free survival is defined as the duration from the date of first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death, whichever comes first.

  4. Part 1 and Part 2: Time to Prostate Specific Antigen (PSA) progression (TTPP) [ Time Frame: Baseline up to 30 days after last dose of study drug ]
    Time to PSA progression is measured from the date of first dose of study drug until the date of PSA progression according to the Prostate Cancer Clinical Trials Working Group (PCWG2) criteria.

  5. Part 1 and Part 2: Blood Culture Assessment of JNJ-64041809 [ Time Frame: Periodically during treatment and up to one year after End of Treatment (EOT) visit ]
    This assessment will include the reporting of surveillance blood cultures (peripherally drawn, and through venous access device [if applicable]) for 1 year after the completion of JNJ-64041809 therapy.

  6. Part 1 and Part 2: Shedding Profile of JNJ-64041809 From Cultured Samples of Feces, Urine, and Saliva [ Time Frame: During cycle 1 (up to 21 days of treatment period) and at EOT visit (within 30 days after last dose) ]
    The shedding of JNJ-64041809 will be studied in cultures of (1) feces by stool or rectal swab, (2) urine samples, and (3) saliva samples.



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

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate with progressive metastatic disease which, in the opinion of the investigator, requires initiation of new treatment. The assessment of disease progression can be based on either PSA rise, new or progressive soft tissue disease (based on computed tomography [CT] or magnetic resonance imaging [MRI] scans), or new or progressive bony disease based on radionuclide bone scan or 18F-sodium fluoride positron emission tomography/computed tomography [NaF PET/CT] scans). Participants being considered for Cohort 2B must, in addition, have primary or metastatic lesions amenable to tumor biopsies
  • Must have received at least 2 prior approved therapies
  • Ongoing androgen depletion therapy with a Gonadotropin Releasing Hormone analog or inhibitor, or orchiectomy (surgical or medical castration)
  • Serum testosterone levels less than (<) 50 nanogram per deciliter (ng/dL) determined within 4 weeks prior to start of study drug
  • For participants previously treated with first generation anti-androgens (ie, flutamide, nilutamide, or bicalutamide), discontinuation of flutamide or nilutamide therapy must occur greater than (>) 4 weeks (>6 weeks for bicalutamide) prior to start of study drug with no evidence of an anti-androgen withdrawal response (no decline in serum PSA)

Exclusion Criteria:

  • Untreated brain metastases. Participants must have completed treatment for brain metastasis, and be neurologically stable off steroids, for at least 28 days prior to first dose of study drug
  • Untreated spinal cord compression
  • History of listeriosis or vaccination with a listeria-based vaccine or prophylactic vaccine (example influenza, pneumococcal, diphtheria, tetanus, and pertussis [dTP/dTAP]) within 28 days of study treatment
  • Known allergy to both penicillin and trimethoprim/sulfamethoxazole. Participants who are allergic to only one of these antibiotics are allowed to enroll
  • Concurrent treatment with anti -Tumor necrosis factor (TNF) alpha therapies, systemic corticosteroids (prednisone dose >10 mg per day or equivalent) or other immune suppressive drugs within the 2 weeks prior to Screening. Steroids that are topical, inhaled, nasal (spray), or ophthalmic solution are permitted

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): NCT02625857


Locations
United States, California
San Francisco, California, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Houston, Texas, United States
United States, Wisconsin
Madison, Wisconsin, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Publications:
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02625857     History of Changes
Other Study ID Numbers: CR107668
64041809PCR1001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: December 9, 2015    Key Record Dates
Last Update Posted: March 1, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Prostatic Neoplasms, Castration-Resistant
JNJ-64041809
Listeria monocytogenes

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