Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Vaccines

Molgramostim

Sargramostim

Monatide (IMS 3015)

Immunologic Factors

Will receive an admixture of the wildtype and epitope enhanced TARP peptides emulsified with Montanide ISA 51 VG and granulocyte-macrophage colony-stimulating factor (GM-CSF). TARP peptide will be administered subcutaneously at weeks 3, 6, 9, 12 and 15 for a total of five vaccinations with a booster dose of vaccine at Weeks 48 and 96

T-cell receptor alternate reading frame protein (TARP) peptide vaccine

Will receive peptide pulsed dendritic cells administered intradermally in two vaccination sites. TARP pulsed dendritic cells will be administered at weeks 3, 6, 9, 12 and 15 for a total of five vaccinations with a booster dose of vaccine at Weeks 48 and 96.

T-cell receptor alternate reading frame protein (TARP) dendritic cell vaccine

Hoyoung M Maeng, M.D.

Background:

* PSA (prostate specific antigen) is a protein found on normal and cancerous prostate cells. Levels of this protein are used to identify men who are at risk for prostate cancer and to monitor responses to treatment in men who have been diagnosed with prostate cancer.
* Research has shown that men who continue to have an elevated PSA level following primary treatment for prostate cancer are at increased risk for cancer progression. Studies have shown that the change in PSA levels over time, or PSA doubling time (PSADT), can be accurate in predicting how quickly the cancer is likely to progress. Individuals with a PSADT of less than 3 months are at extremely high risk for disease progression and death from prostate cancer. Individuals with a PSADT of greater than 15 months have a very low risk of death from prostate cancer.
* T-cell receptor alternate reading frame protein (TARP) is a protein that is found in about 95% of prostate cancers and is known to stimulate the immune system. The TARP prostate cancer vaccine is made from pieces of the TARP protein called peptides and includes peptides that have been modified to make them more effective at stimulating immunity. Although these TARP peptides have been shown to stimulate the immune systems of mice, information is needed to determine if they also stimulate the immune system in humans. Since it is unclear what is the best way to give peptide vaccines, the TARP peptides will be given with substances known to stimulate the immune system or in a vaccine made with the patient s own cells.

Objectives:

* To determine the immune systems response to vaccination with TARP peptides.
* To determine the safety and toxicity of TARP peptide vaccination.
* To determine if vaccination with the TARP prostate cancer vaccine can slow down PSADT in men with an intermediate PSADT of 3 to 15 months.

Eligibility:

* Males 18 years of age and older who have completed their primary treatment for prostate cancer, have stage D0 disease, are Human leukocyte antigen (HLA) A\*0201 positive and who have a PSADT greater than 3 and less than 15 months.

Design:

* Patients will be randomized to one of two treatment arms:
* Arm A will receive the TARP vaccine with other substances that stimulate the immune system.
* Arm B will receive the TARP vaccine that includes a patients own white blood cells.
* First week of study, after screening for eligibility has been completed:
* Day 1: Apheresis procedure to extract white blood cells to test the immune response to the vaccine.
* Day 3: Flu vaccine to allow researchers to determine how well a patients immune system is working.
* Clinic visits in Weeks 3, 6, 9, 12, and 15 for physical examination, blood samples, and administration of the TARP peptide vaccine.
* Physical examination and blood samples only in Weeks 18 and 36.
* Additional blood samples and apheresis procedures in Weeks 24 and 48.
* A 6th dose of TARP peptide vaccine will be administer to those patients who have a response to vaccination at week 24.
* No follow-up or long-term study is associated with this study.

BACKGROUND:

* T-cell receptor alternate reading frame protein (TARP) is expressed by both normal and malignant prostate cancer tissue and is found in about 95% of prostate cancer specimens. TARP is immunogenic and hence is a target antigen for vaccination.
* The immunogenicity of TARP peptides can be augmented through epitope enhancement that is achieved through amino acid substitutions resulting in increased peptide binding affinity.
* Two HLA-A\*0201 TARP peptide epitopes are associated with generation of catalytic T-cell responses: TARP27-35 and TARP29-37. Substitution of Val for Leu at position 9 in TARP29-37, results in a peptide with increased binding affinity (TARP29-37-9V) that induces antigen specific T cells able to recognize wild type and multiple modified TARP peptides. The affinity of the TARP 27-35 peptide, corresponding to a distinct but overlapping epitope, is high enough that no enhancement was required.
* Stage D0 prostate cancer patients have no evidence of visceral or bony metastatic disease but have persistently elevated or rising prostate-specific antigen (PSA) levels (biochemical progression) and are at increased risk for disease progression. Since they lack much of the immune dysfunction associated with the high tumor burden characteristic of end-stage metastatic disease, they are an ideal population in which to study therapeutic vaccination to slow or prevent disease recurrence and progression.
* Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system and are being studied extensively for anti-tumor activity in a broad spectrum of cancer patients.
* As the optimal method for therapeutic immunization with peptide vaccines in patients with cancer is unclear, vaccination with TARP peptides in Montanide ISA 51 VG adjuvant plus Sargramostim will be studied in a randomized fashion with autologous, TARP peptide-pulsed dendritic cells (DCs) in HLA-A\*0201 Stage D0 prostate cancer patients.

OBJECTIVES:

* Determine the safety and toxicity of TARP peptide and TARP peptide-pulsed dendritic cell vaccination in patients with Stage D0 prostate cancer.
* Determine the T-lymphocyte immune responses to TARP peptide vaccination with Montanide ISA 51 VG plus Sargramostim or autologous dendritic cells as measured by tetramer staining, interferon (IFN)-gamma enzyme-linked immune absorbent spot (ELISpot) and (51)Cr release cytotoxic T lymphocytes (CTL) assays.

ELIGIBILITY:

* Males greater than or equal to 18 years of age with histologically confirmed adenocarcinoma of the prostate.
* Must have completed and recovered from all prior definitive therapy (surgery, brachytherapy, cryotherapy or radiotherapy) for the primary tumor, or other definitive-intent local therapy.
* Stage D0 disease with documented biochemical progression documented by rising PSA and no evidence of metastatic disease by physical examination, computed tomography (CT) scan or bone scan.
* Prostate-specific antigen doubling time (PSADT) greater than or equal to 3 months and less than or equal to or equal to 15 months:

  * Patients must have greater than or equal to 3 PSA measurements over greater than or equal to 3 months.
  * The interval between PSA measurements must be greater than or equal to 4 weeks.
* For patients following definitive radiation therapy or cryotherapy: a rise in PSA of \> 2ng/mL above the nadir (per Radiation Therapy Oncology Group (RTOG)-American Society for Radiation Oncology (ASSTRO) consensus criteria).
* For patients following radical prostatectomy: 2 absolute PSA values \> 0.3ng/ml (per National Comprehensive Cancer Network (NCCN) guidelines).
* Non-castrate level of testosterone: greater than or equal to 50 ng/dL (prior androgen deprivation therapy (ADT) allowed; must be greater than or equal to 6 months since last dose of ADT).
* HLA-A\*0201 positive.
* Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky 70-100% and life expectancy greater than or equal to 1 year.
* Hemoglobin greater than or equal to 10.0 gm/dL, white blood cell (WBC) greater than or equal to 2,500/mm(3), absolute lymphocyte count (ALC) greater than or equal to 500/ mm(3), absolute neutrophil count (ANC) greater than or equal to 1,000/mm(3), platelet count greater than or equal to 100,000/mm(3), and prothrombin time (PT)/partial thromboplastin time (PTT) less than or equal to 1.5 times upper limits of normal (ULN) unless receiving clinically indicated anticoagulant therapy; serum glutamic pyruvic transaminase (SGPT)/Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 2.5 times ULN, total bilirubin less than or equal to 1.5 times ULN; creatinine less than or equal to 1.5 times ULN and estimated glomerular filtration rate (GFR) estimated glomerular filtration rate (eGFR) greater than or equal to 60 ml/min.
* Hepatitis B and C negative (unless the result is consistent with prior vaccination or prior infection with full recovery); human immunodeficiency virus (HIV) negative.
* No use of investigational agents within 4 weeks of study enrollment or use of immunosuppressive or immunomodulating agents within 8 weeks of study entry.
* No other concurrent anticancer therapy or prior prostate cancer vaccines expressing TARP or human leukocyte antigen (HLA) A2.
* No alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto). Note: patients receiving medications for urinary symptoms such as Flomax or 5-alpha reductase inhibitors (finasteride and dutasteride) on a chronic stable dose for at least 3 months are allowed.

STUDY DESIGN:

* This is a randomized, prospective, pilot study of vaccination with a mixture of wild type (TARP27-35) and epitope-enhanced (TARP29-37-9V) TARP peptides in HLA-A\*0201 patients with stage D0 prostate cancer.
* Vaccination with TARP peptides admixed with Montanide ISA 51 VG plus Sargramostim administered by deep subcutaneous injection will be compared with vaccination with TARP peptide-pulsed autologous dendritic cells (DCs) administered intradermally.
* Autologous dendritic cells will be matured from peripheral blood monocytes with Sargramostim, interleukin 4 (IL4), IFN-gamma and LPS and pulsed with wild type and epitope-enhanced TARP peptides.
* Apheresis will be performed on all patients at weeks 0, 24, 48 and 96.
* Randomization and assignment to received TARP peptide vaccine with Montanide ISA 51 VG plus Sargramostim given by deep subcutaneous injection or TARP peptide-pulsed autologous DCs given ID will be performed at week 0.
* All patients will receive live, attenuated influenza vaccine (FluMist) when seasonally available at the very end of their week 0 visit as a control vaccine to assess cytotoxic T lymphocyte responses.
* TARP Peptide vaccines will be administered every three weeks at weeks 3, 6, 9, 12, and 15, with a sixth and seventh booster dose of vaccine at Week 48 and 96. Follow-up will be through 144 weeks on study.
* The trial uses an optimal 2-stage design targeting an immunologic response between 10 and 40%. We will initially accrue 9 patients in each arm. If 0-1 patients develop an immunologic response, then no further patients will be enrolled. If 2 or more of these patients develop an immunologic response, we will accrue 11 additional patients for a maximum total of up to 20 patients in each arm. A stopping rule for excessive toxicity will be incorporated.

A Pilot Study of Vaccination With Epitope-Enhanced TARP Peptide and TARP Peptide-Pulsed Dendritic Cells in the Treatment of Stage D0 Prostate Cancer

All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

The number of participants in each arm with positive response determined by 3-fold increase over baseline in the number of positive cells by interferon (IFN) gamma enzyme-linked immunosorbent spot (ELISpot) at week 24. Presence of tumor antigen-specific T cells (positive response) mean the vaccine was able to generate immune response (i.e. immunogenicity) which is a good outcome.

Adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

A three-fold increase over baseline in the number of positive cells by tetramer staining OR Interferon (IFN)-gamma enzyme-linked immune absorbent spot (ELISPOT) assay was considered a positive immunological response.

PSADT response is defined as: a \> 50% increase in calculated PSADT OR a PSADT \> 15 months. Participant's whose PSADT is decreased by \> 50% will be considered PSADT failures. Week 24 PSADT responders will be allowed to receive an additional dose of T-cell receptor alternate reading frame protein (TARP) peptide vaccine at Week 36.

Changes in tumor growth rate constants (g) was calculated from fitting the prostate-specific antigen (PSA) curves to an exponential tumor growth model. Comparison of the median growth rate constant to 75th percentile \[upper quartile\]) of the estimated g of individual subjects pre- and post-TARP vaccination. The Tumor Growth Rate Constant was calculated using a regression-growth equation: f(t) = exp(-d x t) + exp(g x t) - 1, where exp is the base of the natural logarithm, e = 2.7182..., and f(t) is the PSA measurement at time t in days, normalized to (divided by) the PSA measurement at day 0, the time at which treatment is commenced. Rate constant d (decay, in days-1) represents the exponential decrease/regression rate constant of the PSA signal during therapy. Rate constant g (growth, also in days-1) represents the exponential growth/re-growth rate constant of the tumor during treatment.

National Cancer Institute (NCI)

Principal Investigator

T-cell receptor alternate reading frame protein (TARP) peptide vaccine: Will receive an admixture of the wildtype and epitope enhanced TARP peptides emulsified with Montanide ISA 51 VG and granulocyte-macrophage colony-stimulating factor (GM-CSF). TARP peptide will be administered subcutaneously at weeks 3, 6, 9, 12 and 15 for a total of five vaccinations with a booster dose of vaccine at Weeks 48 and 96.

Arm A Montanide ISA 51 VG and Granulocyte-macrophage Colony-stimulating Factor (GM-CSF)

Arm B Autologous Dendritic Cell Vaccine

T-cell receptor alternate reading frame protein (TARP) dendritic cell vaccine: Will receive peptide pulsed dendritic cells administered intradermally in two vaccination sites. TARP pulsed dendritic cells will be administered at weeks 3, 6, 9, 12 and 15 for a total of five vaccinations with a booster dose of vaccine at Weeks 48 and 96.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Baseline Prostate-Specific Antigen (PSA)

"PSA slope log" calculated using Memorial Sloan Kettering Cancer Center Prostate Cancer Nomograms (http://nomograms.mskcc.org/Prostate/PsaDoublingTime.aspx) Slope log represents the speed of change of a series of values. Thus, it is reported without any units as it is with a concept of ratio which does not have any unit by its nature. The clinical meaning of PSA slope change would be decrease/increase of the "speed(velocity)" of changes in PSA, not the changes in PSA values. Decreasing PSA slope after the investigational treatment would mean the PSA rise is slower than pre-treatment baseline.

Pre-Treatment Slope Log Prostate-Specific Antigen (PSA)

Pre-Treatment Prostate-Specific Antigen Doubling Time (PSADT)

Dr. Hoyoung Maeng

8/21 participants in Arm A and 4/20 participants in Arm B did not have samples available to analyze.

Number of Participants With a Positive Immune Response Following Vaccination Determined by Interferon (IFN) Gamma Enzyme-linked Immunosorbent Spot (ELISpot)

Grade 1 Injection site reaction/extravasation changes definitely related to drug

Grade 2 Injection site reaction/extravasation changes definitely related to drug

No Grades 1-5 possibly and probably related to drug

No Grades 3-5 definitely related to drug

Grades 1-5 Adverse Events Possibly, Probably, or Definitely Related to Drug

Week 0

Week 12

Week 24

Number of Participants With an Immunological Response of Chromium 51 (51Cr) Release Measured by Tetramer Staining OR Interferon (IFN)-Gamma Enzyme-linked Immune Absorbent Spot (ELISPOT) Assay

Week 12: ≥ 50% increase in calculated PSADT OR a PSADT > 15 months

Week 24: ≥ 50% increase in calculated PSADT OR a PSADT > 15 months

Week 36: ≥ 50% increase in calculated PSADT OR a PSADT > 15 months

Week 48: ≥ 50% increase in calculated PSADT OR a PSADT > 15 months

Week 12: PSADT is decreased by > 50%

Week 24: PSADT is decreased by > 50%

Week 36: PSADT is decreased by > 50%

Week 48: PSADT is decreased by > 50%

PSA Doubling Time (PSADT) Response and Failure

Pre-vaccine

Post-vaccine

Arm A Montanide ISA 51 VG and granulocyte-macrophage colony-stimulating factor (GM-CSF): T-cell receptor alternate reading frame protein (TARP) peptide vaccine: Will receive an admixture of the wildtype and epitope enhanced TARP peptides emulsified with Montanide ISA 51 VG and granulocyte-macrophage colony-stimulating factor (GM-CSF). TARP peptide will be administered subcutaneously at weeks 3, 6, 9, 12 and 15 for a total of five vaccinations with a booster dose of vaccine at Weeks 48 and 96.and Arm B Autologous Dendritic Cell Vaccine: T-cell receptor alternate reading frame protein (TARP) peptide vaccine: Will receive an admixture of the wildtype and epitope enhanced TARP peptides emulsified with Montanide ISA 51 VG and granulocyte-macrophage colony-stimulating factor (GM-CSF). TARP peptide will be administered subcutaneously at weeks 3, 6, 9, 12 and 15 for a total of five vaccinations with a booster dose of vaccine at Weeks 48 and 96.

All Participants on Arm A and Arm B

Data was only available with participants combined for this outcome measure.

Change in Tumor Growth Rate Constant: Pre-versus Post T-cell Receptor Alternate Reading Frame Protein (TARP) Vaccination

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0).

Overall Study

Participants of African Ancestry with elevated serum prostate specific antigen of (Bullet)3ng/ml or positive digital rectal examination or strong family history.

Yolanda McKinney, R.N.

Ismail B Turkbey, M.D.

National Cancer Institute Referral Office

Background:

Prostate cancer (PCa) is one of the most common cancers in American men; it is a leading cause of death. Men of African ancestry have a higher rate of prostate cancer, and a higher likelihood of death, compared to men of European ancestry. The reasons for these higher rates are not known; they may include genetic and environmental factors. Better screening methods are needed.

Objective:

To test an imaging technology called multiparametric magnetic resonance imaging (mpMRI) for detecting prostate cancer in men of African ancestry.

Eligibility:

Men of African ancestry aged 35 years or older with prostate cancer and/or a strong family history of prostate cancer.

Design:

Participants will be screened. They will have a physical exam with blood and urine tests.

Participants will have an mpMRI. They will lie on a narrow bed that slides into a large cylinder. They will lie still for about 45 minutes. They will hear loud noises during the scan; they may wear earplugs or headphones to muffle the sound. Some participants may have a dye injected into a vein.

If the scan indicates participants risk of prostate cancer is medium or high, they will have a biopsy: The area will be numbed, and samples of tissue will be removed from the prostate. The biopsy will be done within 6 months.

If the scan indicates participants risk of prostate cancer is low, they will not have a biopsy.

All participants will be followed for 5 years. They and/or their local doctors will be contacted once a year for follow-up. Additional mpMRIs may be recommended.

...

Background:

* Prostate cancer (PCa) is the most common non-dermatologic malignancy among American men and is a leading cause of cancer mortality. Men of African Ancestry (AA) have a 1.8- fold higher incidence of prostate cancer and a 2.2-fold higher likelihood of death when compared to men of European Ancestry. The predominant factor in the increased death rate is the increased incidence of cancer. The underlying reasons for the increase in incidence are controversial but likely include genetic and environmental factors.
* One strategy to counteract the effects of increased cancer incidence in a given patient population is to utilize earlier and/or more intense screening as it leads to earlier diagnosis and potentially better outcomes.
* Multiparametric MRI (mpMRI) is a proven useful tool in the diagnosis of prostate cancer but access to high quality mpMRI in communities of color is often limited.
* For individuals who are members of communities of color, high quality prostate MRI is a limited resource and insurance coverage is often denied. Given the high risk of prostate cancer in these communities, the benefits of screening with mpMRI and mpMRI guided biopsies could be significant as it could enable earlier diagnosis.

Objective:

-To compare results of mpMRI and mpMRI guided biopsy in diagnosing clinically significant prostate cancer between men of African Ancestry from hospitals providing medical care for communities of color (e.g., Howard University Hospital, Washington Hospital Center) with the population of self-referred participants seen at NIH who are mostly of European Ancestry.

Eligibility:

* Age \>35 years
* Self-identified men of African Ancestry
* Elevated serum prostate specific antigen (PSA) of \>=3ng/ml and/or positive digital rectal examination and/or strong family history of cancer

Design:

* This is a prospective single arm observational study.
* Up to 345 prostate biopsy na(SqrRoot) ve participants will be recruited to evaluate the use of mpMRI and mpMRI guided biopsy in diagnosing localized clinically significant prostate cancer among men of African Ancestry.
* Study participants will be referred by hospitals that mainly provide medical care for communities of color (e.g., Howard University Hospital, Washington Hospital Center).
* Participants will undergo a state-of-the-art mpMRI of the prostate in the Molecular Imaging Branch, NCI.
* If a suitable lesion (Prostate Imaging Reporting and Data System (PI-RADS \>=3) is identified, mpMRI/transrectal ultrasound (TRUS) fusion guided and standard of care systematic TRUS guided biopsies of the prostate will be performed within 6 months after the mpMRI. Participants with no PI-RADS score \>=3 lesions at baseline mpMRI will not have a biopsy but will be followed for 5 years.
* Participants with a positive baseline mpMRI will be in follow-up for 5 years and have phone/virtual visits occurring annually. Prostate cancer related records and overall 5 year survival status of the participants will be monitored during these follow up visits. If clinically indicated and per referring physician, additional follow up MRIs and PSAs may be obtained annually or bi-annually.

Study of Rates of Prostate Cancer Diagnosis in Men of African Ancestry Using MRI and MRI Guided Biopsy

Observational Study of Rates of Prostate Cancer Diagnosis in Men of African Ancestry Using MRI and MRI Guided Biopsy

.All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

To compare results of mpMRI and mpMRI guided biopsy in diagnosing clinically significant prostate cancer between men of African Ancestry (AA) from hospitals providing medical care for communities of color (e.g., Howard University Hospital, Washington Hospital Center) with the population of self-referred participants seen at NIH who are mostly Caucasian.

To provide data to insurers that supports reimbursement of MRI in men of African Ancestry in order to improve access to care.

To use and further develop artificial intelligence (AI) algorithms to predict for clinically significant prostate cancer in men of African Ancestry based on MRI and clinical features as well as genomic risk scores.

To evaluate prostate cancer status and overall survival in mid-term (5 years) follow up course after baseline MRI

To evaluate genomic sequencing of diagnosed tumors in men of African Ancestry and compare it to the population of self-referred participants to the NCI which is predominantly Caucasian.

To evaluate the predictive value of the polygenic risk score (PRS) in predicting clinically significant prostate cancer in men of African Ancestry.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Pilot Study of Vaccination With Epitope-Enhanced TARP Peptide and TARP Peptide-Pulsed Dendritic Cells in the Treatment of Stage D0 Prostate Cancer	NCT00972309	Prostate Specif... Prostate Neopla...	T-cell receptor... T-cell receptor...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Study of Rates of Prostate Cancer Diagnosis in Men of African Ancestry Using MRI and MRI Guided Biopsy	NCT05872503	Prostate Specif... Positive Digita... Strong Family H... Prostatic Neopl...		35 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Study of Rates of Prostate Cancer Diagnosis in Men of African Ancestry Using MRI and MRI Guided Biopsy	NCT05872503	Prostate Specif... Positive Digita... Strong Family H... Prostatic Neopl...		35 Years - 120 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for prostate specific antigens