Trial to Evaluate Safety and Immunogenicity of INO-5150 Alone or With INO-9012 in Men With Prostate Cancer

• Sponsor: Inovio Pharmaceuticals
• Information provided by (Responsible Party): Inovio Pharmaceuticals

Study Description

Brief Summary:

This is a phase I, open-label trial to evaluate the safety and immunogenicity of INO 5150 alone or in combination with INO-9012 when delivered intramuscularly (IM) followed by electroporation (EP) in men with biochemically relapsed prostate cancer.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Biological: 2mg INO-5150 and electroporation device CELLECTRA®-5P; Biological: 8.5mg INO-5150 and electroporation device CELLECTRA®-5P; Biological: 2mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P; Biological: 8.5mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P; Device: Electroporation using CELLECTRA®-5P	Phase 1

Detailed Description:

Phase I, open label study of INO-5150 (DNA plasmids encoding prostate specific antigen (PSA) and prostate specific membrane antigen (PSMA)) alone or co-administered with INO-9012 (IL-12 plasmid) delivered intramuscularly followed by EP using the CELLECTRA®-5P device in adult males with biochemically relapsed prostate cancer following definitive local therapy (e.g. prostatectomy, external beam radiation, or brachytherapy). Four injections will be administered to approximately 60 eligible subjects who consent to participate in the study. Subjects will be monitored for safety and immunogenicity through Week 72.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	62 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Phase I, Open-label Trial to Evaluate the Safety and Immunogenicity of INO-5150 Alone or in Combination With INO-9012 in Men With Biochemically Relapsed (PSA) Prostate Cancer
Study Start Date :	July 2015
Actual Primary Completion Date :	December 12, 2017
Actual Study Completion Date :	December 12, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A; 2mg INO-5150 and electroporation device CELLECTRA®-5P	Biological: 2mg INO-5150 and electroporation device CELLECTRA®-5P; 2mg INO-5150 delivered IM followed by electroporation using CELLECTRA®-5P; Device: Electroporation using CELLECTRA®-5P; Electroporation device CELLECTRA®-5P
Experimental: Arm B; 8.5mg INO-5150 and electroporation device CELLECTRA®-5P	Biological: 8.5mg INO-5150 and electroporation device CELLECTRA®-5P; 8.5 mg INO-5150 delivered IM followed by electroporation using CELLECTRA®-5P; Device: Electroporation using CELLECTRA®-5P; Electroporation device CELLECTRA®-5P
Experimental: Arm C; 2mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P	Biological: 2mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P; 2mg INO-5150 plus 1 mg INO9012 delivered IM followed by electroporation using CELLECTRA®-5P; Device: Electroporation using CELLECTRA®-5P; Electroporation device CELLECTRA®-5P
Experimental: Arm D; 8.5mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P	Biological: 8.5mg INO-5150 plus 1mg INO-9012 and electroporation device CELLECTRA®-5P; 8.5mg INO-5150 plus 1 mg INO9012 delivered IM followed by electroporation using CELLECTRA®-5P; Device: Electroporation using CELLECTRA®-5P; Electroporation device CELLECTRA®-5P

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of INO-5150 alone or with INO-9012 delivered via IM EP ( Incidence of adverse events, Injection site reactions, Changes in safety laboratory parameters) [ Time Frame: 72 weeks ]
   1. Incidence of adverse events (all, severe, [NCI CTCAE v4.03] and serious) classified by system organ class (SOC), preferred term, severity, and relationship to study medication and schedule
   2. Injection site reactions
   3. Changes in safety laboratory parameters .
2. Antigen specific immune response of INO-5150 alone or with INO-9012 delivered via IM EP [ Time Frame: 72 weeks ]
   Antigen specific cellular immune responses

Secondary Outcome Measures :

1. PSA response rate by PSA testing [ Time Frame: 72 weeks ]
   PSA response

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 90 Years (Adult, Older Adult)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Men aged 18 to 90 years with a histologic diagnosis of prostate cancer;

2. c. Biochemical recurrence following local therapy, either surgery or radiation. Rising PSA defined as:

   • After definitive surgery, e.g.

     • After radical prostatectomy, two PSA measurements of ≥ 1.0 ng/mL at least one week apart;
     • After cryosurgery, two PSA measurements of ≥ 2.0 ng/mL at least one week apart;
     • Other definitive surgical procedures may be permissible upon the approval of the medical monitor OR
   • After radiation therapy (e.g., external beam radiation, brachytherapy, or salvage/adjuvant radiation therapy after surgery), two post radiation PSA measurements level of nadir plus 2.0 ng/mL at least one week apart.;

3. Serum testosterone level:

   i) Subjects with no history of androgen deprivation therapy:

   • A single measurement greater than 150 ng/dL or 5.2 nmol/L within 3 months of enrollment

   ii) Subjects with a history of androgen deprivation therapy (either in adjuvant or biochemical relapse setting):

   • The two most recent measurements of serum testosterone prior to enrollment must fulfill the following criteria:

     • Both measurements are greater than 150 ng/dL or 5.2 nmol/L;
     • The two measurements are spaced at least 14 days apart;
     • Both must be measured within 3 months of enrollment;
4. Normal electro cardio gram (ECG) or ECG with no clinically significant findings;

5. Adequate bone marrow, hepatic, and renal function tests within 30 days prior to enrollment:

   • CBC (except platelets and hemoglobin), serum chemistry, liver panel, and CPK values ≤ Grade 1 abnormality as defined in CTCAE v 4.03 dated June 14, 2010
   • Platelets ≥ 75,000 /mL;
   • Hemoglobin ≥ 9.0 g/dL;
6. No desire or plans to father new children during the study and/or have a prior vasectomy

Exclusion Criteria:

1. PSA doubling time (PSA-DT) of ≤ 3 months, using 2 PSA values at least 4 weeks apart, calculated according to the Memorial Sloan-Kettering Cancer Center nomogram (https://www.mskcc.org/nomograms/prostate/psa-doubling-time);
2. Clinical or radiologic evidence of distant metastatic disease other than small volume (<1.5 cm) nodes, this should be tested within 12 months from enrollment;
3. Receipt of investigational therapy in a clinical trial setting within 30 days of enrollment;
4. Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome;
5. Prior major surgery or radiation therapy within 4 weeks of enrollment;
6. Any prior chemotherapy, except short-course neo-adjuvant or adjuvant chemotherapy that had been stopped for at least 6 weeks prior to Study enrollment;
7. Active AIDS / HIV infection, clinically uncontrolled immune deficiency disorders;
8. Clinically uncontrolled autoimmune disorders, transplant recipients who depend on immunosuppressive therapy, other immunosuppressive conditions including any concurrent condition requiring immunosuppressive/immunomodulating agents;
9. Recipient of any blood product and immunotherapy (such as anti-PD1, anti-PDL-1 and anti-CTLA4) within 3 months of enrollment;

Contacts and Locations

Locations

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United States, Maryland
Chesapeake Urology Research Associates
Baltimore, Maryland, United States, 21204
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Nebraska
GU Research Network, LLC/ Urology Cancer Center
Omaha, Nebraska, United States, 68130
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10065
United States, North Carolina
University of North Carolina Lineberger Cancer Center
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44915
United States, Pennsylvania
Sidney Kimmel Cancer Center - Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
UPMC
Pittsburgh, Pennsylvania, United States, 15232
United States, South Carolina
Carolina Urologic Research Center
Myrtle Beach, South Carolina, United States, 29572
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109

Sponsors and Collaborators

Inovio Pharmaceuticals

Investigators

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Study Director:	Ildi Csiki, MD, PH.D.	Inovio Pharmaceuticals

More Information

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Responsible Party:	Inovio Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT02514213 History of Changes
Other Study ID Numbers:	PCa-001
First Posted:	August 3, 2015
Last Update Posted:	December 26, 2017
Last Verified:	December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No
Plan Description:	combined results when available will be made available

Keywords provided by Inovio Pharmaceuticals:

PSA

Additional relevant MeSH terms:

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