Prostate CancerPhase 1NCT02411786
A Phase I Study of a DNA Vaccine Encoding Androgen Receptor Ligand-Binding Domain (AR LBD) +/-GMCSF
A Phase 1 study testing pTVG-AR and gm-csf in people with Prostate Cancer, run by University of Wisconsin, Madison at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- pTVG-AR and gm-csf
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 3 sitesUnited States
- Study dates
- 24 Aug 2015to 28 Nov 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- Participant with a prior history of a second malignancy are eligible provided they have been treated with curative intent and have been free of disease greater than three years. There will be no exclusion for patients with a history of basal cell carcinoma, squamous cell skin cancer, or other in situ carcinoma that has been adequately treated.
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
University of Washington Seattle Cancer Care Alliance
Seattle, Washington, 98109
About this study
Official title: A Phase I Study of a DNA Vaccine Encoding Androgen Receptor Ligand-Binding Domain (AR LBD), With or Without Granulocyte Macrophage Colony-Stimulating Factor Adjuvant, in Patients With Metastatic Prostate Cancer
The purpose of this study is to determine if a vaccine called pTVG-AR can enhance the participant's immune response against prostate cancer.
- Conditions
- Prostate Cancer
- Being tested
- pTVG-AR, gm-csf
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pTVG-ARBiological
Also called pTVG-AR vaccine
Given ID
gm-csfBiological
Also called Recombinant human GM-CSF, rhGM-CSF
Given ID
| Study group | Role | What they receive |
|---|---|---|
| pTVG-AR biweekly | Experimental | pTVG-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. Receives: Biological: pTVG-AR |
| pTVG-AR staggered biweekly | Experimental | pTVG-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. Receives: Biological: pTVG-AR |
| pTVG-AR with rhGM-CSF biweekly | Experimental | pTVG-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. Receives: Biological: pTVG-AR; Biological: gm-csf |
| pTVG-AR with rhGM-CSF staggered biweekly | Experimental | pTVG-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. Receives: Biological: pTVG-AR; Biological: gm-csf |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: From first immunization to Week 72
Immune Response Rate
Measured: From first immunization to Week 72
Secondary outcomes (6)
Median Progression-Free Survival
Median time to PSA progression will be determined as a function of the date the participant started on androgen deprivation and as a function of treatment start date (week 0). Development of new metastases or discontinuation of study to begin other therapy, while not expected to precede a PSA progression endpoint, would also constitute a progression endpoint.
Measured: From first immunization to Week 72
18-Month Progression-Free Survival
Measured: 18 months
The proportion of patients with a T-cell immune response.
Generation of AR LBD-specific peptide-specific CD8+ T cells as defined by ELISPOT and tetramer staining
Measured: From first immunization to Week 72
The number of patients that generate antigen specific tolerance
Antigen-specific tolerance generation following multiple immunizations
Measured: 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
Measured: From first immunization to Week 72
Association between development of antigen-specific T cells and 18-month progression-free survival
Measured: From first immunization to Week 72
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2015 (estimated)
- Study start24 Aug 2015
- Primary completion1 May 2019
- Study completion28 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Madison Vaccines Incorporated
- Responsible party
- Sponsor
- Investigators
- Douglas G. McNeel, M.D., Ph.D., Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02411786
- Sponsor's protocol ID
- UW14072
- Other IDs
- 2014-1456, A534260, SMPH/MEDICINE/MEDICINE*H, NCI-2015-00808
- Status last verified
- Feb 2021
- First submitted
- 27 Mar 2015
- Last updated
- 4 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 32513836
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of a DNA Vaccine Encoding Androgen Receptor Ligand-Binding Domain (AR LBD), With or Without Granulocyte Macrophage Colony-Stimulating Factor Adjuvant, in Patients With Metastatic Prostate Cancer
- ClinicalTrials.gov ID
- NCT02411786
- Acronym / sponsor ID
- UW14072
- Conditions
- Prostate Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Madison Vaccines Incorporated
- Study start
- 24 Aug 2015 (actual)
- Primary completion
- 1 May 2019 (actual)
- Study completion
- 28 Nov 2020 (actual)
- First posted
- 8 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if a vaccine called pTVG-AR can enhance the participant's immune response against prostate cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| pTVG-AR biweekly | Experimental | Biological: pTVG-ARpTVG-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 | Experimental | Biological: pTVG-ARpTVG-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 | Experimental | Biological: pTVG-AR, Biological: gm-csfpTVG-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 | Experimental | Biological: pTVG-AR, Biological: gm-csfpTVG-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pTVG-ARAlso: pTVG-AR vaccineGiven ID | Biological | pTVG-AR biweekly, pTVG-AR staggered biweekly, pTVG-AR with rhGM-CSF biweekly, pTVG-AR with rhGM-CSF staggered biweekly |
| gm-csfAlso: Recombinant human GM-CSF, rhGM-CSFGiven ID | Biological | pTVG-AR with rhGM-CSF biweekly, pTVG-AR with rhGM-CSF staggered biweekly |
Primary outcome
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
Time frame: From first immunization to Week 72
Immune Response Rate
Time frame: From first immunization to Week 72
6 secondary outcomes
Median Progression-Free Survival
Time frame: From first immunization to Week 72
18-Month Progression-Free Survival
Time frame: 18 months
The proportion of patients with a T-cell immune response.
Time frame: From first immunization to Week 72
The number of patients that generate antigen specific tolerance
Time frame: 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
Time frame: From first immunization to Week 72
Association between development of antigen-specific T cells and 18-month progression-free survival
Time frame: From first immunization to Week 72
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Results publication: PubMed 32513836Kyriakopoulos 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.
- University of Wisconsin Carbone Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Douglas G. McNeel, M.D., Ph.D. principal investigator
University of Wisconsin, Madison
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing pTVG-AR and gm-csf in people with Prostate Cancer, run by University of Wisconsin, Madison at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: From first immunization to Week 72). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02411786, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2021.