Assessment of Novel Biomarkers in Patients With Metastatic Castration Resistant Prostate Cancer
I. Perform molecular analysis of plasma samples from 25 patients with metastatic prostate
cancer collected before and during treatment of the disease with abiraterone acetate
(Zytiga) or enzalutamide (Xtandi).
II. Perform molecular characterization of circulating tumor cells (CTCs) and plasma
collected from 75 patients with progressing advanced metastatic prostate cancer.
OUTLINE: Patients are assigned to 1 of 2 groups based on the timing of specimen collection.
GROUP I: Previously collected plasma samples are analyzed for ctDNA via polymerase chain
reaction (PCR) and next generation sequencing (NSG).
GROUP II: Patients undergo collection of blood samples before and following systemic therapy
for analysis of CTC enumeration, ribonucleic acid (RNA) expression, and ctDNA via PCR and
4P-14-7 - Phase II Randomized, Placebo-Controlled Trial of PROSTVAC? (PSA-TRICOM) in Patients with Clinically Localized Prostate Cancer Undergoing Active Surveillance
An alternative and novel approach for delaying disease progression in men on active surveillance is immunotherapy. This is a Phase II randomized, placebo-controlled, double-blind trial of PROSTVA (a poxviral vaccine), in patients with clinically localized prostate cancer undergoing active surveillance. We plan to recruit men with a diagnosis of localized prostate cancer within 24 months prior to enrollment who are being monitored by active surveillance.
Available data suggest that PROSTVAC improved the overall survival in patients with castration-resistant prostate cancer and the survival benefit increased with less advanced or less aggressive disease.
The primary objectives of this study are to determine the effects of PROSTVAC on the change (from pre- to post-intervention) in CD8+ and CD4+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies and the correlation between the change in CD8+ and the change in PSA.
Men with clinically localized prostate cancer undergoing active surveillance.
The study agent is PROSTVAC. Participants will receive subcutaneous injection of PROSTVAC or placebo in the study clinic. Participants will be randomly assigned (2:1) to PROSTVAC or placebo. One injection of PROSTVAC-V (or placebo) at baseline. Six injections of PROSTVAC-F (or placebo) over 140 days.
Prostate tissue immune infiltrate - Circulating immune cell subsets - PSA doubling time
Tumor extent and grade, and Safety and feasibility.
Study subjects will be followed for 30 days after the end-of-intervention biopsy or 30 days after the last study dose is given, if no end-of-intervention biopsy was performed.
The primary analysis will be based on the participants with available endpoint data. Multiple imputation techniques based on chained equations will be performed to handle missing outcomes. The analysis based on the imputed datasets will be treated as secondary.
A Randomized, Phase II Clinical Trial of a Controlled Diet Prior to Selected Chemotherapy Treatment in Breast and Prostate Cancer to Evaluate the Impact on Toxicity and Efficacy
I. To obtain preliminary estimates of the impact of a restricted diet on toxicity and
efficacy of chemotherapy for breast and prostate cancer.
II. To evaluate the compliance with a controlled diet intervention.
III. To investigate changes in plasma insulin, glucose, insulin-like growth factor 1 (IGF1)
and IGF binding protein (IGFBP) levels in subjects who consume a restricted diet compared to
Patients are randomized to 1 or 2 treatment arms.
ARM I: Patients eat a special low-calorie diet during 3 days prior to chemotherapy, during
the 12 weeks of chemotherapy, and 24 hours after chemotherapy. Patients are provided with
all meals and all food to be consumed and maintain a diary of the food consumed and
appropriate amounts. Patients meet with the study dietician within 3 weeks of enrollment
and prior to, or on the day of, their first course of chemotherapy on study and at the start
of each subsequent course.
ARM II: Patients eat a normal diet and receive dietary advice which may include consultation
with a nutritionist. Patients maintain a diary of the food consumed and appropriate amounts.
A Phase III Prospective Randomized Trial of Dose-Escalated Radiotherapy With or Without Short-Term Androgen Deprivation Therapy for Patients With Intermediate-Risk Prostate Cancer
- Demonstrate an overall survival (OS) advantage in patients with intermediate-risk
prostate cancer treated with dose-escalated radiotherapy (RT) with versus without
short-term androgen-deprivation therapy (ADT).
- Determine whether the addition of ADT to dose-escalated RT versus RT alone improves
clinical failures, biochemical failure by the "nadir +2", freedom from failure, rate of
salvage ADT, and prostate cancer-specific mortality in these patients.
- Estimate the magnitude of benefit of ADT with respect to OS in patients treated with
different RT modalities (i.e., external-beam radiation therapy alone vs low-dose rate
brachytherapy boost vs high-dose rate brachytherapy boost).
- Compare acute and late treatment adverse events of these regimens and correlate these
events with the presence or absence of pre-existing comorbidity as documented by the
Adult Comorbidity Evaluation 27 assessment.
OUTLINE: This is a multicenter, dose-escalation study of radiotherapy. Patients are
stratified according to number of risk factors (1 vs 2-3), comorbidity (ACE-27 grade ≥ 2 vs
< 2), and radiotherapy (RT) modality (dose-escalated external-beam RT [EBRT] vs EBRT and
low-dose rate brachytherapy boost vs EBRT and high-dose rate brachytherapy boost). Patients
are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo EBRT* once daily on days 1-5 for about 9 weeks (44 treatments).
Some patients instead receive EBRT with high-dose rate or low-dose rate brachytherapy
implant on days 1-5 for about 5 weeks (25 treatments). NOTE: *Type of RT is at
discretion of treating physician and may include either 3D-conformal RT or
- Arm II: Patients receive androgen-deprivation therapy comprising luteinizing-hormone
releasing-hormone (LHRH) agonist (leuprolide, goserelin, buserelin, or triptorelin)
subcutaneously or as an injection every 1 to 3 months AND an oral antiandrogen therapy
(flutamide 3 times daily or bicalutamide once daily) for 6 months. Beginning 8 weeks
after the first LHRH injection, patients undergo radiotherapy as in arm I.
After completion of study therapy, patients are followed up periodically.
Randomized, Double-Blind Phase III Study of Pazopanib vs. Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease Following Metastatectomy
I. To evaluate disease-free survival with pazopanib (pazopanib hydrochloride) as compared to
placebo, defined as the time from randomization to the development of recurrent disease,
second primary cancer (other than localized breast, localized prostate, or non-melanoma skin
cancer) or death from any cause for patients with metastatic renal cell carcinoma (RCC) with
no evidence of disease following metastasectomy.
I. To describe the overall survival of patients with advanced RCC randomly assigned to
receive placebo or pazopanib for one year following metastasectomy to no evidence of disease
II. To describe treatment and (at recurrence) disease-related adverse events in the two
III. To analyze quality-adjusted time without symptoms of disease or treatment (Q-TWiST) for
subjects in the two treatment arms.
IV. To characterize changes in patient-reported fatigue and (at recurrence) kidney
cancer-related symptoms during and following treatment with pazopanib compared to placebo.
V. To explore the association between plasma trough levels of pazopanib and disease-free and
VI. To prospectively bank preserved tissue from primary tumors and associated metastatic
sites in patients with RCC.
OUTLINE: Patients are randomized to 1of 2 treatment arms.
ARM I: Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28.
Treatment repeats every 28 days for up to 13 courses in the absence of disease progression
or unacceptable toxicity.
ARM II: Patients receive placebo PO QD on days 1-28. Treatment repeats every 28 days for up
to 13 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for the first
two years, every 6 months for the next 3 years, and then annually up to 10 years.
Exercise and Whey Protein Supplementation as Adjunctive Therapy for Patients With Prostate Cancer Receiving Androgen Deprivation Therapy
I. To determine feasibility of conducting a resistance training (RT) and supplementation
program in this population, determine patient adherence and inter-patient variability, and
estimate the necessary effect sizes for a larger study.
I. To examine the effects of a high intensity RT program, with and without whey protein
supplement (WPS), on lean body mass (LBM). Enhancing LBM will increase muscle strength,
endurance, and physical function leading to improved quality of life.
I. To examine the effects of a high intensity RT program with and without WPS on muscle
strength, endurance, physical function, and quality of life.
II. To examine changes in lymphocyte glutathione (GSH) and the pharmacodynamics of WPS with
and without high intensity RT.
OUTLINE: Patients are randomized to 1 of 4 arms. ARM I: Patients receive whole body
high-intensity RT thrice weekly and whey protein supplementation orally (PO) daily for 12
ARM II: Patients receive whole body RT as in Arm I.
ARM III: Patients receive whey protein supplementation as in Arm I.
ARM IV: Patients receive no intervention for 12 weeks. After 12 weeks, patients may receive
whole body RT as in Arm II.
After completion of study treatment, patients are followed up periodically.
A Phase III Trial of Short Term Androgen Deprivation With Pelvic Lymph Node or Prostate Bed Only Radiotherapy (SPPORT) in Prostate Cancer Patients With a Rising PSA After Radical Prostatectomy
- To determine whether the addition of short-term androgen deprivation (STAD) to prostate
bed radiotherapy (PBRT) improves freedom from progression (FFP) (i.e., maintenance of a
prostate-specific antigen [PSA] less than the nadir+2 ng/mL, absence of clinical
failure, and absence of death from any cause) for 5 years, over that of PBRT alone in
men treated with salvage radiotherapy after radical prostatectomy.
- To determine whether STAD, pelvic lymph node radiotherapy (PLNRT), and PBRT improves
FFP over that of STAD+PBRT and PBRT alone in men treated with salvage radiotherapy
after radical prostatectomy.
- To compare the rates of a PSA ≥ 0.4 ng/mL and rising at 5 years after randomization
(secondary biochemical failure endpoint), the development of hormone-refractory disease
(3 rises in PSA during treatment with salvage androgen-deprivation therapy), distant
metastasis, cause-specific mortality, and overall mortality.
- To compare acute and late morbidity based on Common Toxicity Criteria for Adverse
Effects (CTCAE), v. 3.0.
- To measure the expression of cell kinetic, apoptotic pathway, and angiogenesis-related
genes in archival diagnostic tissue to better define the risk of FFP, distant failure,
cause-specific mortality, and overall mortality after salvage radiotherapy for prostate
cancer, independently of conventional clinical parameters now used.
- To quantify blood product-based proteomic and genomic (single nucleotide polymorphisms)
patterns and urine-based genomic patterns before and at different times after treatment
to better define the risk of FFP, distant failure, cause-specific mortality, and
overall mortality after salvage radiotherapy for prostate cancer, independently of
conventional clinical parameters now used.
- To assess the degree, duration, and significant differences of disease-specific
health-related quality of life (HRQOL) decrements among treatment arms.
- To assess whether mood is improved and depression is decreased with the more aggressive
therapy if it improves FFP.
- To collect paraffin-embedded tissue blocks, serum, plasma, urine, and buffy coat cells
for future translational research analyses.
- To assess whether an incremental gain in FFP and survival with more aggressive therapy
outweighs decrements in the primary generic domains of HRQOL (i.e., mobility, self
care, usual activities, pain/discomfort, and anxiety/depression).
- To evaluate the cost-utility of the treatment arm demonstrating the most significant
benefit (in terms of the primary outcome) in comparison with other widely accepted
cancer and non-cancer therapies.
- To assess associations between serum levels of beta-amyloid and measures of cognition
and mood and depression.
- An exploratory aim is to assess the relationship(s) between the American Urological
Association Symptom Index (AUA SI) and urinary morbidity using the CTCAE v. 3.0 grading
OUTLINE: Patients are stratified according to seminal vesicle involvement (yes vs no),
prostatectomy Gleason score (≤ 7 vs 8-9), pre-radiotherapy PSA (≥ 0.1 and ≤ 1.0 ng/mL vs >
1.0 and < 2.0 ng/mL), and pathology stage (pT2 and margin negative vs all others). Patients
are randomized to 1 of 3 treatment arms.
- Arm I (prostate bed radiotherapy [PBRT] alone): Patients undergo PBRT once daily, 5
days a week, Monday through Friday, for approximately 7-8 weeks (36 to 39 fractions).
- Arm II (PBRT and short-term androgen-deprivation [STAD]): Beginning 2 months before the
start of PBRT, patients undergo STAD, using a combination of antiandrogen and
luteinizing hormone-releasing hormone (LHRH) agonist therapy, for a total of 4-6
months. Patients receive antiandrogen therapy comprising either oral flutamide 3 times
daily or oral bicalutamide once daily for at least 4 months (started within 1-14 days
prior to the LHRH agonist and ending the last day of radiotherapy ± 14 days). Patients
receive LHRH agonist injection beginning concurrently with or 2 weeks after the start
of antiandrogen therapy. LHRH agonist injection consists of analogs approved by the FDA
(or by Health Canada for Canadian institutions) (e.g., leuprolide, goserelin,
buserelin, or triptorelin) and may be given in any possible combination (may be given
as a single 4-month injection and one to two 1-month injection[s], two 3-month
injections, or a 6-month injection), such that the total LHRH agonist treatment time is
4-6 months. Approximately 2 months after beginning of STAD, patients undergo PBRT as in
- Arm III (Pelvic lymph node radiotherapy [PLNRT], PBRT, and STAD): Beginning 2 months
before the start of radiotherapy, patients receive STAD therapy as in arm II.
Approximately 2 months after beginning of STAD, patients undergo PBRT and PLNRT once
daily, 5 days a week, Monday through Friday, for approximately 5 weeks (25 fractions)
followed by PBRT only once daily, 5 days a week for approximately 2-3 weeks (11-14
Patients complete the American Urological Association Symptom Index (AUA SI) questionnaire
prior to protocol treatment, at week 6 of radiotherapy, and then periodically after
completion of study therapy.
After completion of study therapy, patients are followed up every 3 months for 1 year, every
6 months for 4 years, and then annually thereafter.
Phase III Trial of Enzalutamide (NSC# 766085) Versus Enzalutamide, Abiraterone and Prednisone for Castration Resistant Metastatic Prostate Cancer
Patients are randomized to one of two treatment groups: enzalutamide or enzalutamide,
abiraterone and prednisone. Treatment will continue until disease progression or
unacceptable toxicity. Patients are followed for clinical outcomes for a maximum of 5 years
post study treatment. The primary and secondary objectives are described below.
1. Primary Objective:
To compare the overall survival of patients with progressive metastatic
castration-resistant prostate cancer (CRPC) treated with either enzalutamide only or
enzalutamide with abiraterone and prednisone
2. Secondary Objectives:
- To assess the grade 3 or higher toxicity profile and compare safety by treatment
- To assess and compare post-treatment prostate-specific antigen (PSA) declines by
- To compare radiographic progression free survival defined by Prostate Cancer
Working Group 2 (PCWG2), and objective response rate, by treatment arm.
- To test for radiographic progression free survival (rPFS) treatment interaction in
predicting overall survival.
- To assess pre- and post-treatment measures of tumor burden and bone activity using
sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT)
and technetium (Tc) methylene diphosphonate (MDP) bone scintigraphy and correlate
these measures with overall survival.
- To develop and validate prognostic and predictive models of overall survival that
include baseline clinical and molecular markers.
Phase 2 Trial of phenelzine in non-metastatic recurrent prostate cancer
Prostate cancer is the most common non-cutaneous cancer diagnosed in men in the United State with a projected annual incidence of ~29,000 deaths in 2013. For most patients, prostate cancer is adequately treated with primary therapy which may include radiation, surgery (radical prostatectomy, or active surveillance. However, in about one third of patients, cancer recurs following primary therapy usually manifested as an asymptomatic rise in plasma prostate specific antigen (PSA) level. Biochemical recurrence (BCR) defines patients with a confirmed elevation in PSA in the absence of clinically detectable metastatic disease. Given the slow disease course of BCR prostate cancer and the frequent occurrence of other life-altering co-morbidities in this patient population, BCR is a very common condition for which there are no clear standards in terms of the composition of timing of potential treatments. We hypothesize that phenelzine will exert an anti-cancer effect demonstrated by decreasing PSA values in biochemical recurrent prostate cancer patients. In this trial, a dose of 60 mg daily is set as the target dose level based on patient tolerance drawn from the experience in patients with depression. The primary objective in this study is to assess the proportion of patients with biochemically recurrent prostate cancer treated with phenelzine who achieve a PSA decline of >/= 50% from baseline. The secondary objectives of this study are to monitor for potential toxicities and/or beneficial effects of phenelzine in prostate cancer without depression, mania or other primary psychiatric diagnosis; to assess time to radiographic disease progression for patients with recurrent prostate cancer treated with phenelzine. The exploratory objective is to collect blood and other samples to study the relationship between MAO activity, biomarkers and prostate cancer. The study population for this study will be men with asymptomatic non-metastatic prostate cancer. A total of 46 patients will be enrolled. 23 with non-castrate circulating androgen levels (testosterone > 50 ng/dl); 23 with castrate levels of circulating androgens (testosterone <50 ng/dl). The dose of phenelzine will be 30mg orally twice a day. The starting dose will be 15 mg daily escalated to 30 mg twice a day over 15 days (Please see section 4.1). Laboratory assessments, including plasma PSA at baseline and following every 28 day cycle. Imaging assessment including CT scans of chest/abdomen/pelvis and bone scan at baseline and every 12 weeks or as clinically indicated.
0C-13-4: A Phase I, Open-Label, Multiple-Ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of avelumab (MSB0010718C) in Subjects with Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications
This is a Phase I, open-label, dose-escalation trial with consecutive parallel group expansion in nonsmall cell lung cancer (NSCLC), metastatic breast cancer (MBC), colorectal cancer (CRC), castrate-resistant prostate cancer (CRPC), melanoma, and ovarian cancer to assess clinical activity of avelumab (MSB0010718C) .USC will participate only in the expansion part of the study. Avelumab (MSB0010718C) is an experimental drug, which belongs to a family of molecules called anti-PD-L1 antibodies. PD-L1 is a cell surface protein, found in different human tumor types, which is considered to be able to inhibit an anti-tumor response of the immune system. Compared with anti-PD-1 antibodies that target T-cells, anti-PD-L1 antibodies that target tumor cells are expected to have less side effects, including a lower risk of autoimmune-related safety issues. Based on this theory, fully human IgG1 anti-PD-L1 antibody (MSB0010718C) has been produced.Subjects will receive avelumab (MSB0010718C) intravenously as a 1-hour infusion once every 2 weeks until confirmed CR (complete response), confirmed progression, unacceptable toxicity, or any reason for withdrawal from the trial or IMP (Investigational Medical Product) occurs Expansion phase will enroll 380 subjects in total out of which 30 will be from USC. Primary objective will be to determine the safety and clinical activity of avelumab (MSB0010781C) Primary endpoint is Occurrence of DLTs during the first 3 weeks of treatment in the dose escalation part.Subjects at the end-of-treatment visit will be followed up for disease progression (CT / MRI scans every 12 weeks) up to 1 year.Descriptive statistics and graphical representations will be the main analysis tools