Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

NCT02499835 | Completed Phase 1 Results DMC FDA Drug

• 6 other identifiers: UW150142015-0453NCI-2015-01154A534260SMPH\MEDICINE\HEM-ONCProtocol Version 3/19/2018
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized pilot trial studies vaccine therapy and pembrolizumab in treating patients with prostate cancer that does not respond to treatment with hormones (hormone-resistant) and has spread to other places in the body (metastatic). Vaccines made from deoxyribonucleic acid (DNA), such as pTVG-HP plasmid DNA vaccine, may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as pembrolizumab, may find tumor cells and help kill them. Giving pTVG-HP plasmid DNA vaccine and pembrolizumab may kill more tumor cells.

Conditions

Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (5)

• Incidence of Adverse Events, Using the National Cancer Common Terminology Criteria, Version 4

  Toxicities will be summarized by type, as reported in the adverse events section, and total events calculated per arm.

  Up to 23 months (Up to 12 months after completion of study treatment)

• 6-month Progression Free Survival Rate

  6-month progression-free survival rate will be reported for each arm, and for overall combined study. Progression is at least a 20% increase in the sum of diameters of target lesions and a 0.5cm minimum increase, or the appearance of one or more new lesions. In order to evaluate the 6-month progression-free rate as a function of baseline time point (pretreatment or 3-months post treatment), analysis will be conducted using two different baseline values: date of randomization, and 3-months disease assessment. Central tendency is appropriate due to 20% increase and measurements being a mean of growth across time periods.

  6 months

• Median Time to Radiographic Progression

  Median time to radiographic progression will be estimated for each, and for both study arms combined, using Kaplan-Meier method. Log-rank test will be used to perform comparison of time to radiographic progression between study arms. A one-sided 0.10 significance level will be used to conduct the comparison of the 6-month progression-free survival rate and time to radiographic progression between study arms. In order to evaluate the median time to radiographic progression as a function of baseline time point (pretreatment or 3-months post treatment), analysis will be conducted.

  Up to 2 years

• Number of Participants Who Have an Objective Response

  Will be calculated for each study arm and for all arms combined. Complete response is the disappearance of all target lesions. Partial response is at least 30% decrease in the sum of diameters of target lesions.

  Up to 2 years

• Number of Participants Who Have a PSA Response

  Will be calculated for each study arm and for all arms combined. PSA complete response is a decrease in PSA to ,0.2 ng/mL; partial response is greater than or equal to 50% reduction in baseline PSA.

  Up to 2 years

Secondary Outcomes (4)

• PAP-specific Immune Response

  Up to 2 years

• PAP-specific T-cell Response

  Up to 2 years

• PD-1 Expression

  Up to day 85

• PD-L1 Expression

  Up to day 85

Study Arms (4)

Arm I (pTVG-HP plasmid DNA vaccine, concurrent pembrolizumab)

EXPERIMENTAL

Patients receive pTVG-HP plasmid DNA vaccine ID every other week on days 1, 15, 29, 43, 57, and 71 and pembrolizumab IV over 30 minutes every 3 weeks on days 1, 22, 43, and 64.

Biological: Pembrolizumab; Biological: pTVG-HP Plasmid DNA Vaccine

Arm II (pTVG-HP plasmid DNA vaccine, sequential pembrolizumab)

EXPERIMENTAL

Patients receive pTVG-HP plasmid DNA vaccine ID as in Arm I and pembrolizumab IV over 30 minutes every 3 weeks on days 85, 106, 127, and 148.

Biological: Pembrolizumab; Biological: pTVG-HP Plasmid DNA Vaccine

Extended Treatment Arm III

EXPERIMENTAL

pTVG-HP (100 μg) with rhGM-CSF (208 μg) administered intradermally (i.d.) every 3 weeks, for a maximum of 16 doses. Pembrolizumab 2 mg/kg, with a maximum dose of 200 mg, administered intravenously every 3 weeks, for a maximum of 16 doses, beginning on day 1 after the first pTVG-HP vaccination.

Biological: Pembrolizumab; Biological: pTVG-HP Plasmid DNA Vaccine

Extended Treatment Arm IV

EXPERIMENTAL

pTVG-HP (100 µg) with rhGM-CSF (208 µg) administered intradermally (i.d.) every 2 weeks, for a maximum of 24 doses Pembrolizumab 2 mg/kg, with a maximum dose of 200 mg, administered intravenously every 4 weeks, for a maximum of 12 doses, beginning on day 1 after the first pTVG-HP vaccination

Biological: Pembrolizumab; Biological: pTVG-HP Plasmid DNA Vaccine

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: 1374853-91-4, Immunoglobulin G4, Anti-(Human Programmed Cell Death 1), Lambrolizumab, Keytruda, MK-3475, SCH 900475

Arm I (pTVG-HP plasmid DNA vaccine, concurrent pembrolizumab); Arm II (pTVG-HP plasmid DNA vaccine, sequential pembrolizumab); Extended Treatment Arm III; Extended Treatment Arm IV

pTVG-HP Plasmid DNA Vaccine BIOLOGICAL

Given ID

Arm I (pTVG-HP plasmid DNA vaccine, concurrent pembrolizumab); Arm II (pTVG-HP plasmid DNA vaccine, sequential pembrolizumab); Extended Treatment Arm III; Extended Treatment Arm IV

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)
• Metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (CT of abdomen/pelvis, bone scintigraphy)
• Castrate-resistant disease, defined as follows:
• All patients must have received (and be receiving) standard of care androgen deprivation treatment (surgical castration versus gonadotropin-releasing hormone \[GnRH\] analogue or antagonist treatment); subjects receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study
• Patients may or may not have been treated previously with a nonsteroidal antiandrogen; for patients previously treated with an antiandrogen, they must be off use of anti-androgen for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to registration; moreover, subjects who demonstrate an anti-androgen withdrawal response, defined as a \>= 25% decline in PSA within 4-6 week of stopping a nonsteroidal antiandrogen, are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal
• Patients must have a castrate serum level of testosterone (\< 50 ng/dL) within 6 weeks of day 1
• Progressive disease while receiving androgen deprivation therapy defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) bone scan criteria or Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 during or after completing last therapy:
• PSA: at least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, with the final value \>= 2.0 ng/mL
• Measurable disease: \>= 50% increase in the sum of the cross products of all measurable lesions or the development of new measurable lesions; the short axis of a target lymph node must be at least 15 mm by spiral CT to be considered a target lesion
• Non-measurable (bone) disease: the appearance of two or more new areas of uptake on bone scan (or fluorine F 18 sodium fluoride \[NaF\] PET/CT) consistent with metastatic disease compared to previous imaging during castration therapy; the increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or magnetic resonance imaging \[MRI\])
• Prior treatment with abiraterone or enzalutamide is permitted, but patients must have been off prior corticosteroid treatment for at least 3 months
• Life expectancy of at least 6 months
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• White blood cells (WBC) \>= 2000/mm\^3
• Absolute neutrophil count (ANC) \>= 1000/mm\^3

You may not qualify if:

• Small cell or other variant (non-adenocarcinoma) prostate cancer histology, unless there is evidence that the tumor expresses PAP
• Patients may not be receiving other investigational agents or be receiving concurrent anticancer therapy other than standard androgen deprivation therapy
• Concurrent bisphosphonate therapy is not excluded, however patients should not start bisphosphonate therapy while on this study; those patients already receiving bisphosphonate therapy should continue at the same dosing and schedule as prior to study entry
• Rapidly progressive symptomatic metastatic disease, as defined by the need for increased opioid analgesics within one month of registration for the treatment of pain attributed to a prostate cancer metastatic lesion; patients receiving opioids must receive approval from the principal investigator (PI) for eligibility
• Treatment with any of the following medications within 28 days of registration, or while on study, is prohibited:
• Systemic corticosteroids (at doses over the equivalent of 5 mg prednisone daily) - not permitted within 3 months of registration; inhaled, intranasal or topical corticosteroids are acceptable
• Prostate cancer (PC)-SPES
• Saw palmetto
• Megestrol
• Ketoconazole
• alpha-reductase inhibitors - patients already taking 5-alpha-reductase inhibitors prior to 28 days prior to registration may stay on these agents throughout the course of therapy, but these should not be started while patients are on study
• Diethyl stilbestrol
• Abiraterone
• Enzalutamide
• Radium 223 (Xofigo)

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Prostate Cancer Foundation: collaborator
• Madison Vaccines Incorporated: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (3)

• McNeel DG, Eickhoff JC, Wargowski E, Zahm C, Staab MJ, Straus J, Liu G. Concurrent, but not sequential, PD-1 blockade with a DNA vaccine elicits anti-tumor responses in patients with metastatic, castration-resistant prostate cancer. Oncotarget. 2018 May 22;9(39):25586-25596. doi: 10.18632/oncotarget.25387. eCollection 2018 May 22.

  PMID: 29876010 RESULT

• McNeel DG, Eickhoff JC, Wargowski E, Johnson LE, Kyriakopoulos CE, Emamekhoo H, Lang JM, Brennan MJ, Liu G. Phase 2 trial of T-cell activation using MVI-816 and pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC). J Immunother Cancer. 2022 Mar;10(3):e004198. doi: 10.1136/jitc-2021-004198.

  PMID: 35277461 RESULT

• Scarpelli M, Zahm C, Perlman S, McNeel DG, Jeraj R, Liu G. FLT PET/CT imaging of metastatic prostate cancer patients treated with pTVG-HP DNA vaccine and pembrolizumab. J Immunother Cancer. 2019 Jan 30;7(1):23. doi: 10.1186/s40425-019-0516-1.

  PMID: 30700328 DERIVED

Related Links

• Clinical Trials at the University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

pembrolizumab; Immunoglobulin G

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Douglas McNeel, MD
• Organization: University of Wisconsin Carbone Cancer Center

dm3@medicine.wisc.edu

608-263-4198

Study Officials

• Douglas G McNeel, MD PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Model Details: Once at least 12 subjects per arm are accrued to Arms 1 and 2, and Arm 3 is open to accrual, accrual will occur only to Arm 3 (other arms will be closed). Extended treatment Arm 4 will open only when Arm 3 has met accrual.

Study Record Dates

• First Submitted: July 14, 2015
• First Posted: July 16, 2015
• Study Start: July 1, 2015
• Primary Completion: August 9, 2021
• Study Completion: July 27, 2023
• Last Updated: August 1, 2023
• Results First Posted: December 1, 2022

Record last verified: 2023-07

Locations

US (1)