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

Primary Purpose

Prostatic Neoplasms, Castration-Resistant

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

JNJ-64041809 (Cohort 1A and 1B)

JNJ-64041809 (Cohort 2A and 2B)

About this trial

This is an interventional treatment trial for Prostatic Neoplasms, Castration-Resistant focused on measuring Prostatic Neoplasms, Castration-Resistant, JNJ-64041809, Listeria monocytogenes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Dose Cohort 1A and 1B

Dose Cohort 2A and 2B

Arm Description

JNJ-64041809 will be administered intravenously (IV) once every 21 days.

Outcomes

Primary Outcome Measures

Part 1: Incidence of Dose-limiting-toxicity (DLT)

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 (%).

Part 2: Antigen-specific T-cell Response

Biomarker studies will be performed to evaluate immune responses to the vaccine after the first intravenous (IV) immunization.

Part 1 and Part 2: Incidence of Adverse Events (AEs)

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

Part 1 and Part 2: Objective Response Rate (ORR)

Objective response rate is defined as the percentage of participants who achieve complete response (CR) or partial response (PR), as assessed by the investigator.

Part 1 and Part 2: Duration of Response (DOR)

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.

Part 1 and Part 2: Progression-free Survival (PFS)

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.

Part 1 and Part 2: Time to Prostate Specific Antigen (PSA) progression (TTPP)

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.

Part 1 and Part 2: Blood Culture Assessment of JNJ-64041809

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.

Part 1 and Part 2: Shedding Profile of JNJ-64041809 From Cultured Samples of Feces, Urine, and Saliva

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.

Full Information

NCT ID

NCT02625857

First Posted

December 7, 2015

Last Updated

August 8, 2019

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT02625857

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2019

Overall Recruitment Status

Completed

Study Start Date

December 10, 2015 (Actual)

Primary Completion Date

July 3, 2018 (Actual)

Study Completion Date

July 3, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostatic Neoplasms, Castration-Resistant

Keywords

Prostatic Neoplasms, Castration-Resistant, JNJ-64041809, Listeria monocytogenes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose Cohort 1A and 1B

Arm Type

Experimental

Arm Description

JNJ-64041809 will be administered intravenously (IV) once every 21 days.

Arm Title

Dose Cohort 2A and 2B

Arm Type

Experimental

Arm Description

JNJ-64041809 will be administered intravenously (IV) once every 21 days.

Intervention Type

Biological

Intervention Name(s)

JNJ-64041809 (Cohort 1A and 1B)

Intervention Description

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).

Intervention Type

Biological

Intervention Name(s)

JNJ-64041809 (Cohort 2A and 2B)

Intervention Description

JNJ-64041809 will be administered intravenously (IV) once every 21 days at the recommended dose as determined in Cohort 1A or 1B.

Primary Outcome Measure Information:

Title

Part 1: Incidence of Dose-limiting-toxicity (DLT)

Description

Time Frame

first 21 days after the first infusion

Title

Part 2: Antigen-specific T-cell Response

Description

Biomarker studies will be performed to evaluate immune responses to the vaccine after the first intravenous (IV) immunization.

Time Frame

up to 1 year

Title

Part 1 and Part 2: Incidence of Adverse Events (AEs)

Description

Time Frame

From signing of informed consent form to 30 days after last dose of study drug

Secondary Outcome Measure Information:

Title

Part 1 and Part 2: Objective Response Rate (ORR)

Description

Objective response rate is defined as the percentage of participants who achieve complete response (CR) or partial response (PR), as assessed by the investigator.

Time Frame

Baseline up to 30 days after last dose of study drug

Title

Part 1 and Part 2: Duration of Response (DOR)

Description

Time Frame

Baseline up to 30 days after last dose of study drug

Title

Part 1 and Part 2: Progression-free Survival (PFS)

Description

Time Frame

Baseline up to 30 days after last dose of study drug

Title

Part 1 and Part 2: Time to Prostate Specific Antigen (PSA) progression (TTPP)

Description

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.

Time Frame

Baseline up to 30 days after last dose of study drug

Title

Part 1 and Part 2: Blood Culture Assessment of JNJ-64041809

Description

Time Frame

Periodically during treatment and up to one year after End of Treatment (EOT) visit

Title

Part 1 and Part 2: Shedding Profile of JNJ-64041809 From Cultured Samples of Feces, Urine, and Saliva

Description

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.

Time Frame

During cycle 1 (up to 21 days of treatment period) and at EOT visit (within 30 days after last dose)

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

City

San Francisco

State/Province

California

Country

United States

City

Baltimore

State/Province

Maryland

Country

United States

City

Saint Louis

State/Province

Missouri

Country

United States

City

Nashville

State/Province

Tennessee

Country

United States

City

Houston

State/Province

Texas

Country

United States

City

Madison

State/Province

Wisconsin

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22595054

Citation

Le DT, Dubenksy TW Jr, Brockstedt DG. Clinical development of Listeria monocytogenes-based immunotherapies. Semin Oncol. 2012 Jun;39(3):311-22. doi: 10.1053/j.seminoncol.2012.02.008.

Results Reference

background

PubMed Identifier

15365184

Citation

Brockstedt DG, Giedlin MA, Leong ML, Bahjat KS, Gao Y, Luckett W, Liu W, Cook DN, Portnoy DA, Dubensky TW Jr. Listeria-based cancer vaccines that segregate immunogenicity from toxicity. Proc Natl Acad Sci U S A. 2004 Sep 21;101(38):13832-7. doi: 10.1073/pnas.0406035101. Epub 2004 Sep 13.

Results Reference

background

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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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