Prostate Cancer Clinical Trial
Official title:
Phase I/II Trial of Androgen Deprivation, With or Without pTVG-AR, and With or Without T-Cell Checkpoint Blockade, in Patients With Newly Diagnosed, High-Risk Prostate Cancer
The current protocol will examine the use of a plasmid DNA vaccine encoding AR, alone or with T-cell checkpoint blockade, to induce and/or augment therapeutic T-cells following androgen deprivation in patients with newly diagnosed prostate cancer scheduled to undergo prostatectomy. Patients without evidence of metastatic disease, with tissue remaining from a pre-treatment biopsy, and who are being considered for standard treatment by prostatectomy, will be invited to participate and will be on study for up to 15 months.
Status | Recruiting |
Enrollment | 60 |
Est. completion date | December 2028 |
Est. primary completion date | December 2026 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Histologically confirmed adenocarcinoma of the prostate - Patients must be considered candidates for prostatectomy as per standard of care - High-risk patients for recurrent disease, with high risk defined based on one of the following criteria: - Gleason score 7 and baseline serum prostate specific antigen (PSA) > 20 ng/mL - Gleason score > 7 - Life expectancy of at least 12 months at screening - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. - Adequate hematologic, renal and liver function as evidenced by the following within 4 weeks of day 1: - Absolute neutrophil count (ANC) > 1000 / mm3 - HgB > 9.0 gm/dL independent of transfusion - Platelets > 100,000 / mm3 - Creatinine < 2.0 mg/dL - Aspartate aminotransferase (AST), Alanine transaminase (ALT) < 2.5 x institutional upper limit of normal (ULN) - Total bilirubin < 2x institutional ULN (NOTE: in subjects with Gilbert's syndrome, if total bilirubin is >2x ULN, measure direct and indirect bilirubin and if direct bilirubin is within normal range, subject may be eligible) - No known history of HIV 1 and 2, HTLV-1, or active Hepatitis B or Hepatitis C - Must have adequate tissue (ten 5µm unstained formalin-fixed paraffin-embedded (FFPE) sections containing prostate cancer) remaining from pre-treatment diagnostic prostate biopsy for research purposes - Patients must be willing to undergo large-volume blood draws (up to 200mL per time point) for the investigational component of this trial - For those patients who are sexually active, they must be willing to use barrier contraceptive methods during the period of treatment on this trial - Patients 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 - Ability to comply with all study procedures and willingness to remain supine for 120 minutes during imaging Exclusion Criteria: - Small cell or other variant (non-adenocarcinoma) prostate cancer histology - Prior treatment for prostate cancer, including androgen deprivation therapy (ADT), orchiectomy, antiandrogens, ketoconazole, abiraterone acetate or enzalutamide - Prior radiation to the prostate - Patients may not be receiving other investigational agents or be receiving concurrent anticancer therapy other than the treatment-prescribed androgen deprivation therapy - Treatment with any of the following medications while on study is prohibited, washout period not required except as indicated: - Systemic corticosteroids (at doses over the equivalent of 10 mg prednisone daily) - not permitted within 3 months of registration; inhaled, intranasal or topical corticosteroids are acceptable - PC-SPES - Herbal supplements that have been shown to modulate testosterone or androgen signaling (e.g. Saw Palmetto) are not allowed while on study - Megestrol - Ketoconazole - 5-a-reductase inhibitors - patients already taking 5-a-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 - Diethylstilbesterol - Any other non-study hormonal agent or supplement being used with the intent of cancer treatment - Major surgery within 4 weeks of registration is prohibited - Active cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within 6 months of registration - Patients with known psychological or sociological conditions, addictive disorders or family problems, which would preclude compliance with the protocol - Patients who have undergone splenectomy - Patients must not have other active malignancies other than non-melanoma skin cancers or carcinoma in situ of the bladder, that have been adequately treated. Subjects with a history of other cancers who have been adequately treated and have been recurrence-free for > 3 years are eligible. - Any other medical intervention or condition, which, in the opinion of the principle investigator (PI) or treating physician, could compromise patient safety or adherence with the study requirements over the primary 3-6 month treatment period. - Patients who have concurrent enrollment on other phase I, II, or III investigational treatment studies cannot be actively receiving treatment and the last dose cannot be within 4 weeks. - Patients who have received a live vaccine within 14 days prior to the first dose of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed - Patients with a history of life-threatening autoimmune disease or active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment - Patients with a history of non-infectious pneumonitis that required corticosteroid treatment, or has current pneumonitis - Patients with a history of allergic reactions to the tetanus vaccine |
Country | Name | City | State |
---|---|---|---|
United States | University of Wisconsin Carbone Cancer Center | Madison | Wisconsin |
Lead Sponsor | Collaborator |
---|---|
University of Wisconsin, Madison | Bristol-Myers Squibb, Madison Vaccines, Inc, National Cancer Institute (NCI), Regeneron Pharmaceuticals, United States Department of Defense |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Number of AR-specific Th1-biased T-cell responses | Summarized in tabular format for each study arm. Fisher's exact test will be used to conduct the comparisons between arms. | up to 15 months on study (1 year after prostatectomy) | |
Other | Change in levels of prostate tissue-infiltrating CD8+T cells | Changes in these levels from the baseline to mid-treatment and post-treatment assessments will be evaluated within each arm using a paired t-test. | baseline, month 3 | |
Other | Change in levels of AR-specific tumor-infiltrating CD8+T cells | Changes in these levels from the baseline to mid-treatment and post-treatment assessments will be evaluated within each arm using a paired t-test. | baseline, month 3 | |
Other | Frequency of CD8+ T cells with memory and effector function | The frequency of CD8+ T cells with memory and effector function will be analyzed and compared between study arms using a generalized linear mixed effects model with subject specific random effects. | up to 15 months on study (1 year after prostatectomy) | |
Other | FLT-PET imaging endpoints: SUVmean | 3'-Deoxy-3'-[18F]Fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) endpoints include mean Standardized Update Value (SUVmean). | baseline and day 45 | |
Other | FLT-PET imaging endpoints: SUVmax | baseline and day 45 | ||
Other | FLT-PET imaging endpoints: SUVtotal | baseline and day 45 | ||
Primary | Pathological Complete Response Rate (pCR) | The pathological complete response will be estimated for each arm and reported along with the corresponding 95% confidence interval which will be constructed using the Wilson score method. Formal comparisons between arms will be conducted using Fisher's exact test. Participants in this study with unknown pathological response will be treated as non-responders in the primary analysis. | at prostatectomy (up to 3 months) | |
Primary | Minimal Residual Disease (MRD) Rate | The MRD rate will be estimated for each arm and reported along with the corresponding 95% confidence interval which will be constructed using the Wilson score method. Formal comparisons between arms will be conducted using Fisher's exact test. Participants in this study with unknown pathological response will be treated as non-responders in the primary analysis. | at prostatectomy (up to 3 months) | |
Primary | Incidence of Adverse Events | Adverse events will be evaluated using the most recent version of the Common Terminology Criteria for Adverse Events (CTCAE). | up to 15 months | |
Primary | Toxicity Rates | Toxicity rates (grade 2, grade 3, grade 4, grade = 2, grade = 3, etc.) will be calculated for each study arm and reported along the corresponding 95% confidence intervals. The 95% confidence intervals will be constructed using the Wilson score method. | up to 15 months | |
Secondary | Progression-Free Survival (PSA) at 1-year | Defined as a serum PSA <0.2 ng/mL at 1 year after prostatectomy, in patients with non-castrate (>25 ng/dL) testosterone levels. | up to 15 months on study (1 year after prostatectomy) | |
Secondary | Residual Cancer Burden (RCB) | RCB will be determined using three-dimensional volume estimation based on the largest cross-sectional tumor dimension and number of cross-sections involved by tumor, corrected for tumor cellularity. The amount of RCB will be summarized for each arm in terms of medians and ranges. Comparisons between arms will be conducted using a nonparametric Wilcoxon rank sum test. Linear regression analysis will be conducted to evaluate whether AR-specific immune response is associated with RCB. | at prostatectomy (up to 3 months) |
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