Provenge With or Without pTVG-HP DNA Booster Vaccine in Prostate Cancer

NCT01706458 | Completed Phase 2 Results DMC

• 5 other identifiers: CO11816A534260SMPH/MEDICINE/MEDICINE*HNCI-2012-020262012-0352
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized pilot clinical trial studies sipuleucel-T with or without deoxyribonucleic acid (DNA) vaccine therapy in treating patients with prostate cancer that has not responded to previous treatment with hormones and has spread to other places in the body. Vaccines may help the body build an effective immune response to kill tumor cells. It is not yet known whether giving sipuleucel-T vaccine works better with or without DNA vaccine therapy in treating prostate cancer.

Conditions

Prostate Cancer

Keywords

Vaccine; pTVG-HP; Prostate Cancer; Castrate Resistant

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Immune Response Following Treatment

  The primary immunological goal of this study was to determine whether booster immunizations with a DNA vaccine encoding PAP could augment the number of PAP-specific effector and memory T cells following treatment with sipuleucel-T, or prolong the duration of detectable T-cell response. All subjects received a tetanus booster immunization prior to beginning the immunization series, providing a separate test of an individual's immune responsiveness. Responses to PSA, a non-target prostate specific protein, were concurrently evaluated, as were responses to GM-CSF, a component of the PA2024 fusion protein used in the preparation of sipuleucel-T.Samples were evaluated for antigen-specific IFNy or granzyme B secretion by ELISPOT, and the detection of statistically significant antigen-specific responses, that were at least 3-fold over the baseline value, and detectable more than once post-treatment, were used to define immune response to a particular antigen.

  12 months

Secondary Outcomes (3)

• Progression-free Survival

  12 months

• Time to Radiographic Disease Progression

  12 months

• Measure Prostate-specific Antigen (PSA) Doubling Time

  12 months

Other Outcomes (6)

• Overall Survival: Median Time to Death From Any Cause

  up to approximately 5 years

• Number of Circulating Tumor Cells

  6 months

• PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine

  12 months

Study Arms (2)

sipuleucel-T

ACTIVE COMPARATOR

Patients receive sipuleucel-T IV on weeks 0, 2, and 4.

Biological: sipuleucel-T

sipuleucel-T with DNA Vaccine

EXPERIMENTAL

Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months.

Biological: sipuleucel-T; Biological: DNA Vaccine

Interventions

sipuleucel-T BIOLOGICAL

Given IV

Also known as: Provenge

sipuleucel-T; sipuleucel-T with DNA Vaccine

DNA Vaccine BIOLOGICAL

Given ID

Also known as: pTVG-HP with rhGM-CSF

sipuleucel-T with DNA Vaccine

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 (computed tomography \[CT\] of abdomen/pelvis, bone scintigraphy)
• Castrate-resistant disease, defined as follows:
• All patients must have received standard of care androgen deprivation treatment before trial entry (surgical castration versus gonadotropin-releasing hormone \[GnRH\] analogue or antagonist treatment), and subjects receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study
• Patients may have been treated previously with a nonsteroidal antiandrogen, with evidence of disease progression subsequently; subjects must be off use of anti-androgen for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to registration
• \*\* 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
• Castration levels of testosterone (\< 50 ng/dL) within 2 weeks of registration
• 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, and each 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 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 \[MRI\])
• Must have \>= 3 serum PSA values obtained over at least a 12 week period of time prior to registration, including the day of screening, to calculate a PSA doubling time; Note: PSA's are not required to be obtained at the same laboratory; use all PSA values that have been done in last 6 months to calculate PSA doubling time
• 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 cell \>= 2000/mm\^3

You may not qualify if:

• Small cell or other variant prostate cancer histology
• Patients may not be receiving other investigational agents or be receiving concurrent anticancer therapy other than androgen deprivation
• Symptomatic metastatic disease, as defined by the need for opioid analgesics 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
• Patients may not have been treated with prior sipuleucel-T
• 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 1 mg prednisone daily); 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
• Any other hormonal agent or supplement being used with the intent of cancer treatment
• External beam radiation therapy within 4 weeks of registration is prohibited, or anticipated need for radiation therapy (e.g. imminent pathological fracture or spinal cord compression) within 3 months of registration

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Dendreon: collaborator

Study Sites (1)

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Wargowski E, Johnson LE, Eickhoff JC, Delmastro L, Staab MJ, Liu G, McNeel DG. Prime-boost vaccination targeting prostatic acid phosphatase (PAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) using Sipuleucel-T and a DNA vaccine. J Immunother Cancer. 2018 Mar 13;6(1):21. doi: 10.1186/s40425-018-0333-y.

  PMID: 29534736 RESULT

Related Links

• University of Wisconsin Carbone Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

sipuleucel-T; Vaccines, DNA; regramostim

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)

Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Recombinant Proteins; Proteins; Amino Acids, Peptides, and Proteins; Vaccines; Biological Products; Complex Mixtures; Antigens; Biological Factors

Results Point of Contact

• Title: Mary Jane Staab - Program Manager
• Organization: UWCCC

mjs@medicine.wisc.edu

608-262-4304

Study Officials

• Douglas McNeel, M.D., PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2012
• First Posted: October 15, 2012
• Study Start: May 20, 2013
• Primary Completion: June 12, 2017
• Study Completion: August 13, 2020
• Last Updated: June 18, 2021
• Results First Posted: July 17, 2018

Record last verified: 2021-05

Locations

US (1)