A Phase I Study of a DNA Vaccine Encoding Androgen Receptor Ligand-Binding Domain (AR LBD) +/-GMCSF
5 other identifiers
interventional
40
1 country
3
Brief Summary
The purpose of this study is to determine if a vaccine called pTVG-AR can enhance the participant's immune response against prostate cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1 prostate-cancer
Started Aug 2015
Typical duration for phase_1 prostate-cancer
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 27, 2015
CompletedFirst Posted
Study publicly available on registry
April 8, 2015
CompletedStudy Start
First participant enrolled
August 24, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
November 28, 2020
CompletedFebruary 4, 2021
February 1, 2021
3.7 years
March 27, 2015
February 2, 2021
Conditions
Outcome Measures
Primary Outcomes (2)
Number and severity of adverse events following serial intradermal vaccinations of a DNA vaccine encoding AR LBD, with or without GM-CSF as an adjuvant, in patients with metastatic prostate cancer
From first immunization to Week 72
Immune Response Rate
From first immunization to Week 72
Secondary Outcomes (6)
Median Progression-Free Survival
From first immunization to Week 72
18-Month Progression-Free Survival
18 months
The proportion of patients with a T-cell immune response.
From first immunization to Week 72
The number of patients that generate antigen specific tolerance
From first immunization to Week 72
Association between pre-existing immune responses to the AR LBD and development of subsequent effector and memory T-cell immune response
From first immunization to Week 72
- +1 more secondary outcomes
Study Arms (4)
pTVG-AR biweekly
EXPERIMENTALpTVG-AR (dose: 100 µg) alone without rhGM-CSF. Administered at weeks 0, 2, 4, 6, 8, and 10 (biweekly) for 6 doses, then administered at week 12, week 24, week 36, and week 48 (quarterly) for 4 doses, or 10 total doses.
pTVG-AR staggered biweekly
EXPERIMENTALpTVG-AR (dose: 100 µg) alone without rhGM-CSF. Administered at weeks 0, 2, 12, 14, 24, 26, 36, 38, 48 and 50 (staggered biweekly schedule) for 10 total doses.
pTVG-AR with rhGM-CSF biweekly
EXPERIMENTALpTVG-AR (dose: 100 µg) with rhGM-CSF (200 µg). Administered at weeks 0, 2, 4, 6, 8, and 10 (biweekly) for 6 doses, then administered at week 12, week 24, week 36, and week 48 (quarterly) for 4 doses, or 10 total doses.
pTVG-AR with rhGM-CSF staggered biweekly
EXPERIMENTALpTVG-AR (dose: 100 µg) with rhGM-CSF (200 µg). Administered at weeks 0, 2, 12, 14, 24, 26, 36, 38, 48 and 50 (staggered biweekly schedule) for 10 total doses.
Interventions
Given ID
Given ID
Eligibility Criteria
You may qualify if:
- Participant must be at least 18 years of age with a histologic diagnosis of adenocarcinoma of the prostate.
- Participant must have metastatic prostate cancer (clinical stage D1 or D2 disease), with previously documented lymph node, soft tissue and/or bone metastases by radiographic imaging (including CT (or MRI) of abdomen and pelvis and bone scintigraphy). Participants in situations in which there is a reasonable clinical suspicion of a second primary tumor (or other non-prostate cancer reason for radiographic abnormalities) are not eligible unless metastatic disease is histologically confirmed to be prostate cancer.
- Participant must have started androgen deprivation therapy (bilateral orchiectomy versus LHRH agonist, and with or without androgen antagonist) at least one month (4 weeks) prior to enrollment and no more than six months (24 weeks) prior to enrollment. Participant must continue the androgen deprivation therapy throughout the study period, and patients are not permitted to change the type of androgen deprivation therapy (e.g. by adding an androgen antagonist) during the course of investigational therapy.
- Participant must have a serum testosterone \< 50 ng/dL demonstrated within 1 month of study entry.
- Participant must either not be a candidate for docetaxel chemotherapy for newly diagnosed metastatic prostate cancer, as determined by their treating oncologist, or have declined this therapy
- Participant must have evidence of response to androgen deprivation as defined by a documented decline in serum PSA values from pre-androgen deprivation treatment baseline and without evidence of PSA progression while on androgen deprivation (defined by PCWG2 criteria as a 25% increase in serum PSA and an absolute increase of 2 ng/mL over nadir).
- Participant who are sexually active must use a reliable form of contraception while on study and for 4 weeks after the last immunization.
- Eastern Cooperative Oncology Group (ECOG) performance score \< 2.
- Participant must have adequate hematologic, renal and liver function as defined by: WBC \> 3000/mm3, hematocrit \> 30%, platelet count \> 100,000/mm3, serum creatinine \< 1.6 mg/dl or a calculated creatinine clearance \> 60 cc/min, and serum bilirubin \< 2.0 mg/dl, within 4 weeks prior to first immunization.
- Participant must be informed of the experimental nature of the study and its potential risks and must sign an IRB-approved written informed consent form indicating such an understanding.
You may not qualify if:
- Small cell or other (non-adenocarcinoma) variant prostate cancer histology.
- Participant cannot have evidence of immunosuppression or have been treated with immunosuppressive therapy, such as chemotherapy, chronic treatment dose corticosteroids (greater than the equivalent of 10 mg prednisone per day), or radiation therapy to \>30% of the bone marrow, within 6 months of the first vaccination. Treatment or salvage radiation therapy encompassing \< 30% of bone marrow must have been completed 4 weeks prior to the first vaccination.
- Seropositive for HIV, hepatitis B (HBV) or hepatitis C (HCV) per participant history.
- Participant previously treated with neoadjuvant and/or adjuvant androgen deprivation (e.g. with radiation therapy) prior to the 6-month eligibility period are allowed, assuming they did not meet criteria for progression (defined by PCWG2 criteria as a 25% increase in serum PSA and an absolute increase of 2 ng/mL over nadir) while on treatment.
- Participant must not be concurrently taking other medications or supplements with known hormonal effects (other than LHRH agonists or non-steroidal anti-androgen), including PC-SPES, megestrol acetate, finasteride, ketoconazole, estradiol, or Saw Palmetto. All other medications with possible anti-cancer effects must be discussed with the Protocol Principal Investigator prior to study entry.
- Participant previously treated with herbal supplements as described in 6.B.5, or other potential or experimental therapies for prostate cancer (apart from LHRH agonists and antiandrogens as described in 6.A.3 above), must have been discontinued these treatments and completed at least a one-month washout prior to first vaccination.
- Participant must not have plans to receive concomitant chemotherapy, other biological or immune therapies, or radiation therapy for the treatment of prostate cancer during the period of study treatment.
- Participant must not have known psychological or sociological conditions, addictive disorders or family problems, which would preclude compliance with the protocol.
- Participant must not have known allergic reactions to GM-CSF or the tetanus vaccine.
- Prior treatment with another experimental anti-tumor vaccine is permissible.
- Participant with unstable or severe intercurrent medical conditions or laboratory abnormalities that would impart, in the judgment of the Protocol Principal Investigator, excess risk associated with study participation or study agent administration.
- Unable or unwilling to undergo two leukapheresis procedures.
- Participant with medical conditions precluding leukapheresis.
- Participant cannot have concurrent enrollment on other phase I, II, or III investigational treatment studies for the treatment of prostate cancer.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Wisconsin, Madisonlead
- Madison Vaccines Incorporatedcollaborator
Study Sites (3)
Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
University of Washington Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792, United States
Related Publications (1)
Kyriakopoulos CE, Eickhoff JC, Ferrari AC, Schweizer MT, Wargowski E, Olson BM, McNeel DG. Multicenter Phase I Trial of a DNA Vaccine Encoding the Androgen Receptor Ligand-binding Domain (pTVG-AR, MVI-118) in Patients with Metastatic Prostate Cancer. Clin Cancer Res. 2020 Oct 1;26(19):5162-5171. doi: 10.1158/1078-0432.CCR-20-0945. Epub 2020 Jun 8.
PMID: 32513836RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Douglas G. McNeel, M.D., Ph.D.
University of Wisconsin, Madison
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 27, 2015
First Posted
April 8, 2015
Study Start
August 24, 2015
Primary Completion
May 1, 2019
Study Completion
November 28, 2020
Last Updated
February 4, 2021
Record last verified: 2021-02