Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Adenocarcinoma

Prostatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Patients undergo proton beam radiation therapy in 15 fractions over 5-6 weeks.

Laboratory Biomarker Analysis

Proton Beam Radiation Therapy

Quality-of-Life Assessment

Steven J Frank

This phase II trial studies the side effects and how well hypofractionated proton beam radiation therapy works in treating patients with prostate cancer that has not spread to nearby lymph nodes or to other parts of the body. Specialized radiation therapy, such as proton beam radiation therapy, that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.

PRIMARY OBJECTIVES:

I. Estimate the incidence of grade 2 gastrointestinal toxicity following the proposed treatment regimens at 2 years post-treatment.

SECONDARY OBJECTIVES:

I. Estimate the change in health related quality of life (HRQOL) following the proposed treatment regimen compared to pre-treatment assessment as defined by Expanded Prostate Cancer Index Composite (EPIC), Utilization of Sexual Medications/Devices, and Medical history/conditions questionnaire.

II. Estimate the rates of acute toxicity of the treatment regimens. III. Estimate the rates of late toxicity at 3, 4, and 5 years post-treatment. IV. Assess the efficacy of hypo-fractionated proton beam therapy, defined by the incidence of a rising prostate-specific antigen (PSA) at 5 years.

V. Determine the rate of local failure by biopsy of the prostate when objective tests, prostate-specific antigen (PSA), magnetic resonance imaging (MRI), digital rectal exam (DRE), suggest relapse.

OUTLINE:

Patients undergo proton beam radiation therapy in 15 fractions over 5-6 weeks.

After completion of study treatment, patients are followed up every 6-12 months for 24 months and then annually until month 60.

Hypofractionated Proton Beam Therapy for Localized Prostate Cancer

Phase II Trial of Hypofractionated Proton Beam Therapy in Men With Localized Prostate Adenocarcinoma

The cumulative incidence of late grade 2 or greater GI toxicity will be estimated with a 95% confidence interval.

Rates of acute toxicity will be assessed.

Rate of late toxicity will be determined.

Incidence of rising PSA will be assessed.

Rate of local failure by biopsy will be evaluated.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Symptoms and General Pathology

Immune System Diseases

Recurrence

Hypersensitivity

All Drugs and Chemicals

Anti-Infective Agents

Hormones

Itraconazole

Hydroxyitraconazole

Clotrimazole

Miconazole

Antifungal Agents

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Hormone Antagonists

Cytochrome P-450 CYP3A Inhibitors

Patients receive twice/day 300mg itraconazole (oral)

Pharmacological Study

Rahul Aggarwal, MD

This phase II trial studies how well itraconazole works in treating patients with biochemically relapsed prostate cancer. Itraconazole may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To determine whether the proportion of patients who achieve a \>= 50% decline in serum prostate-specific antigen (PSA) after 12 weeks of protocol therapy with itraconazole dosed at 300 mg orally (PO) twice daily (BID) is superior to a historical control based upon the observed PSA response proportion in prior studies of non-castrating systemic therapy in men with biochemically relapsed hormone sensitive prostate cancer.

SECONDARY OBJECTIVES:

I. To determine the median time to PSA progression from the start of protocol therapy with itraconazole among men with biochemically relapsed prostate cancer.

II. To determine the median time to clinical progression measured from the start of protocol therapy with itraconazole among men with biochemically relapsed prostate cancer.

III. To determine the median metastasis-free survival measured from the start of protocol therapy in patients treated with itraconazole for biochemically relapsed prostate cancer.

IV. To determine the mean percent change from baseline after 12 weeks of protocol therapy compared with pre-treatment in PSA doubling time.

V. To characterize the safety profile of itraconazole in the biochemically relapsed hormone sensitive prostate cancer population, as graded by Common Toxicity Criteria (CTCAE) version 4.03. All adverse events will be tabulated by grade according to the worst grade experienced.

VI. To determine the mean steady-state itraconazole and hydroxy-itraconazole serum levels after 4 weeks of therapy with itraconazole.

Itraconazole in Treating Patients With Biochemically Relapsed Prostate Cancer

Hedgehog Inhibition as a Non-Castrating Approach to Hormone Sensitive Prostate Cancer: A Phase II Study of Itraconazole in Biochemical Relapse

The number of patients with biochemically relapsed disease after prior definitive local therapy who achieve a ≥ 50% decline from baseline in serum PSA after 12 weeks of therapy with itraconazole, confirmed by repeat measurement at least 2 weeks later.

The mean percent change in PSA doubling time from pre-treatment to after 12 weeks of protocol therapy

PSA progression defined as: 1. If no PSA decline is observed on therapy, PSA progression will be defined as an increase in serum PSA \> 50% above the baseline PSA, and an absolute increase of \> 2 ng/mL above baseline, confirmed by repeat measurement at least 2 weeks later. 2. If PSA declines on therapy, PSA progression will be defined as an increase in serum PSA \> 50% above the nadir PSA on therapy, and an absolute increase \> 2 ng/mL above the nadir, confirmed by repeat measurement at least 2 weeks later. The probability distribution of the time to PSA progression will be estimated using the Kaplan-Meier product limit method measured from the start of protocol therapy. The results will be summarized by the estimated median with 95% confidence intervals.

Clinical progression will be defined as the first occurrence of either the development of metastases or initiation of non-protocol therapy, and will exclude PSA-only progression.

The probability distribution of the time to clinical progression will be estimated using the Kaplan-Meier product limit method measured from the time of start of protocol therapy. The results will be summarized by the estimated median with 95% confidence intervals.

The probability distribution of the time to first metastasis will be estimated using the Kaplan-Meier product limit method measured from the time of start of protocol therapy. The results will be summarized by the estimated median with 95% confidence intervals.

All patients who receive at least one dose of study drug will be analyzed for safety endpoints. All adverse events will be graded and classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4. Percentage of patients with grade 1 or higher, treatment-related adverse events based on the following vital sign assessments will be reported: blood pressure, pulse, respiration rate and temperature.

All patients who receive at least one dose of study drug will be analyzed for safety endpoints. All adverse events will be graded and classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4.. Percentage of patients with grade 1 or higher, treatment-related adverse events based on the following labs will be reported: potassium, sodium, alkaline phosphatase, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Hematocrit, Hemoglobin, platelets, white blood cells, atypical lymphs, basophils, eosinophils, monocytes, neutrophils, blood urea nitrogen, and creatinine.

Descriptive statistics including the mean, standard deviation, and range of steady-state trough serum levels of itraconazole and its active metabolite hydroxy-itraconazole will be determined.

University of California, San Francisco

All patients who received at least one dose of study drug were analyzed for adverse events

Treatment (Itraconazole)

40-49 Years

50-59 Years

60-69 Years

70-79 Years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Years since diagnosis of prostate cancer

Gleason grade ≤ 7 (low/intermediate grade)

Gleason grade > 7 (high grade)

Gleason grade is determined at the time of diagnosis based on pathology review of prostate cancer biopsy or surgical specimen. A higher Gleason grade (\> 7) is associated with a higher chance for disease recurrence and shorter long-term survival.

Gleason Grade at Time of Diagnosis

Time interval from biochemical relapse to study entry

PSA doubling time at the time of study entry

No evaluable data was collected from validated assay. Long term, metastatic disease status data was also not collected.

Number of Patients Who Achieve a Greater Than or Equal to 50% Decline in Serum Prostate Specific Antigen (PSA)

Mean Percent Change in PSA Doubling Time

Median Time to PSA Progression

Only 1 patient displayed clinical progression

Median Time to Clinical Progression

Median Metastasis-free Survival

Blood Pressure

Weight

Pulse

Respiration Rate

Temperature

Percentage of Participants With Treatment-related, Adverse Changes in Vital Signs

Potassium

Alanine aminotransferase

Sodium

Alkaline phosphatase

Total bilirubin

Aspartate aminotransferase

Hematocrit

Hemoglobin

Platelets

White blood cells

Atypical lymphs

Basophils

Eosinophils

Monocytes

Neutrophils

Blood urea nitrogen

Creatinine

Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events

Mean Steady-state Trough Level of Serum Itraconazole

Mean Steady-state Trough Level of Hydroxy-itraconazole

Overall Study

Disease Progression

Vaccines

Metronidazole

Immunologic Factors

Anti-Bacterial Agents

Antiprotozoal Agents

Antiparasitic Agents

Patients receive rilimogene-galvacirepvec SC at baseline and on days 14, 28, 56, 84, 112, and 140.

Patients receive placebo SC at baseline and on days 14, 28, 56, 84, 112, and 140.

Placebo Administration

Rilimogene Galvacirepvec

John K Parsons

This randomized phase II trial studies how well PROSTVAC (prostate-specific antigen \[PSA\]-TRICOM) works in preventing disease progression in patients with prostate cancer undergoing active surveillance. Vaccines made from a person's tumor cells may help the body build an effective immune response to kill tumor cells that express PSA.

PRIMARY OBJECTIVES:

I. To determine the effect of rilimogene-galvacirepvec (PROSTVAC) on the change (from pre to post-intervention) in CD8+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.

II. To determine the effect of PROSTVAC on the change in CD4+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.

SECONDARY OBJECTIVES:

I. To assess the effect of PROSTVAC on PD-L1 positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.

II. To assess the correlation between the change in CD8+ and the change in PSA. III. To assess the effect of PROSTVAC on CD8+, CD4+, and PD-L1 positive cells in the benign portion of the prostate biopsies.

IV. To assess the effect of PROSTVAC on the change in PSA. V. To assess the effect of PROSTVAC on tumor grade (Gleason score). VI. To assess the effect of PROSTVAC on tumor extent (percent of positive random biopsy cores).

VII. To compare the proportion of men on the two study arms with no cancer on post-intervention biopsy.

VIII. To assess the effect of PROSTVAC on the size of the dominant lesion on magnetic resonance imaging (MRI) (largest histopathologically confirmed lesion) in the subgroup of patients with MRIs pre and postintervention.

IX. To assess the effect of PROSTVAC on circulating 15-Mer PSA-specific, MUC-1 and Brachyury-specific T cells.

X. To assess the effect of PROSTVAC on soluble antibodies to tumor-associated antigens.

XI. To assess the immunologic effects of PROSTVAC in prostate tissue using multiplex immunofluorescence.

XII. To assess the safety and feasibility of PROSTVAC in the active surveillance population.

XIII. To assess the effect of PROSTVAC on lower urinary tract symptoms (LUTS) in the active surveillance population.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive rilimogene-galvacirepvec subcutaneously (SC) at baseline and on days 14, 28, 56, 84, 112, and 140.

ARM II: Patients receive placebo SC at baseline and on days 14, 28, 56, 84, 112, and 140.

After completion of study treatment, patients are followed up for 30 days and then at 6 months.

PROSTVAC (PSA-TRICOM) in Preventing Disease Progression in Patients With Localized Prostate Cancer Undergoing Active Surveillance

Phase II Randomized, Placebo-Controlled Trial of PROSTVAC (PSA-TRICOM) in Patients With Clinically Localized Prostate Cancer Undergoing Active Surveillance

change (from pre to post-intervention) in CD8+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.

change (from pre to post-intervention) in CD4+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.

Change (from pre to post-intervention) in PD-L1 positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies

Change (from baseline to 6 months post-intervention) in prostate-specific antigen (PSA)

Change (from pre to post-intervention) in CD8+ positive cells in the benign portion of the prostate biopsies

Change (from pre to post-intervention) in CD4+ positive cells in the benign portion of the prostate biopsies

Change (from pre to post-intervention) in PD-L1 positive cells in the benign portion of the prostate biopsies

Assessed by the proportion of men with an increase in Gleason score to \>= 4+3 from baseline to post-intervention biopsy. The Gleason score is determined by adding the two most common grades. The Gleason score usually ranges from 6 to 10. Higher numbers indicate a faster growing cancer that is more likely to spread.

Assessed by change (from pre to post-intervention) in percent positive random cores

Assessed by the proportion of patients with no cancer on the post-intervention biopsy

Change (from pre to post-intervention) in circulating 15-Mer PSA-specific T cells

Change (from pre to post-intervention) in soluble antibodies to tumor-associated antigens

Change (from baseline to 6 months post-intervention) in International Prostate Symptom Score (IPSS). The IPSS score ranges from 0-35. Higher scores mean a worse symptom.

Patients receive rilimogene-galvacirepvec SC at baseline and on days 14, 28, 56, 84, 112, and 140.

Laboratory Biomarker Analysis: Correlative studies

Rilimogene Galvacirepvec: Given SC

Arm I (Rilimogene-galvacirepvec)

Patients receive placebo SC at baseline and on days 14, 28, 56, 84, 112, and 140.

Laboratory Biomarker Analysis: Correlative studies

Placebo Administration: Given SC

Arm II (Placebo)

Total

Age, Continuous

United States

Region of Enrollment

Sherry Chow, PhD

Participants with tumor present in tissue sections from both the pre and post-intervention biopsies

Change in CD8+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies

Participants with tumor present on the tissue sections from both the pre and post-intervention biopsies were included in the analysis

Change in CD4+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies

Change in PD-L1 Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies

The initial protocol did not include participant follow-up at 6 months post-intervention. Participants with available PSA data at baseline and at 6 months post-intervention were included in the analysis.

Change in Prostate-specific Antigen (PSA)

Participants with benign tissue present in tissue sections from both the pre and post-intervention biopsies were included in the analysis.

Change in CD8+ Positive Cells in the Benign Portion of the Prostate Biopsies

Change in CD4+ Positive Cells in the Benign Portion of the Prostate Biopsies

Change in PD-L1 Positive Cells in the Benign Portion of the Prostate Biopsies

The number of participants analyzed is different from the numbers provided in the Participant Flow Module because 2 participants in the placebo arm did not undergo the post-intervention biopsy to provide the data for the analysis.

Tumor Grade Progression

Change in Tumor Extent

Proportion of Men With no Cancer in the Post-intervention Biopsy

Size of Dominant MRI Lesion

Change in Circulating 15-Mer PSA-specific T Cells

Change in Soluble Antibodies to Tumor-associated Antigens

Immunologic Effects on the Target Organ Using Multiplex Immunofluorescence

The initial protocol did not include participant follow-up at 6 months post-intervention. Participants with available IPSS data at baseline and at 6 months post-intervention were included in the analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hypofractionated Proton Beam Therapy for Localized Prostate Cancer	NCT01950351	Stage I Prostat... Stage II Prosta...	Laboratory Biom... Proton Beam Rad... Quality-of-Life...	18 Years -	M.D. Anderson Cancer Center
Itraconazole in Treating Patients With Biochemically Relapsed Prostate Cancer	NCT01787331	Prostate Adenoc... Recurrent Prost... Stage I Prostat... Stage II Prosta... Stage III Prost...	Itraconazole Laboratory Biom... Pharmacological...	18 Years -	University of California, San Francisco
PROSTVAC (PSA-TRICOM) in Preventing Disease Progression in Patients With Localized Prostate Cancer Undergoing Active Surveillance	NCT02326805	Stage I Prostat... Stage II Prosta...	Laboratory Biom... Placebo Adminis... Rilimogene Galv...	-	National Cancer Institute (NCI)
Hypofractionated Proton Beam Therapy for Localized Prostate Cancer	NCT01950351	Stage I Prostat... Stage II Prosta...	Laboratory Biom... Proton Beam Rad... Quality-of-Life...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for stage i prostate adenocarcinoma ajcc v7