Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Anti-Inflammatory Agents

Antineoplastic Agents

Reproductive Control Agents

Androgens

Hormones

Prednisone

Leuprolide

Goserelin

Prolactin Release-Inhibiting Factors

Bicalutamide

Antineoplastic Agents, Hormonal

Hormone Antagonists

Androgen Antagonists

Androgen Ablation (hormonal therapy before surgery), Cabazitaxel (chemotherapy before surgery), Salvage Surgery (radical prostatectomy), Post-operative Hormonal Therapy, Post-operative Follow-up

All patients will receive luteinizing hormone-releasing hormone (LHRH) agonist therapy (leuprolide or goserelin acetate) concurrent with Cabazitaxel, before surgery. A course of bicalutamide 50 mg daily orally for 14-21 days is recommended for patients starting LHRH agonist therapy and suspected to be at risk for tumor flare, e.g., significant obstructive urinary symptoms and will be optional in other patients.

Androgen Ablation

Intravenous treatment with Cabazitaxel 25 mg/m\^2 is given on day 1 every 21 days. A cycle of chemotherapy will be defined as 21 days. A total of four cycles of combination therapy are planned for a total duration of 12 weeks (before surgery), starting within 3 weeks of protocol entry, to be given concurrent with hormone therapy.

Cabazitaxel

Patients will undergo 4 cycles of chemotherapy in conjunction with LHRH agonist therapy (before surgery) subsequent to which they will have their serum Prostate-specific antigen (PSA), bone scan, abdominal pelvic computed tomography (CT) or magnetic resonance imaging (MRI) repeated. Patients with a detectable metastatic diseases will be removed from the study. Salvage surgery will be performed within 8 weeks after the completion of Cabazitaxel chemotherapy. For patients who achieved undetectable PSA following surgery, androgen deprivation therapy will be discontinued.

Salvage Therapy

All treatment will be given on an outpatient basis. Treatment should start within 3 weeks of protocol entry. All patients will receive androgen ablation with LHRH agonist therapy in conjunction with the 4 cycles of Cabazitaxel for neoadjuvant chemohormonal therapy. Androgen ablative therapy will be discontinued before surgery. A course of bicalutamide 50 mg daily orally for 14-21 days is recommended for patients starting LHRH agonist therapy and suspected to be at risk for tumor flare, e.g., significant obstructive urinary symptoms and will be optional in other patients.

Neoadjuvant Treatment - Hormonal Therapy

All treatment will be given on an outpatient basis and should start within 3 weeks of protocol entry. Intravenous treatment with Cabazitaxel is given on Day 1 every 3 weeks. A cycle of combination therapy will be defined as 3 weeks. A total of 4 cycles of combination therapy are planned before surgery for a total duration of 12 weeks.

Cabazitaxel will be administered before surgery by one-hourly infusions via central or peripheral intravenous access at a dose of 25 mg/m\^2 as a one hour intravenous infusion in combination with oral prednisone 10 mg administered daily throughout Cabazitaxel treatment. It is advised that all patients receiving Cabazitaxel have a reliable form of venous access, e.g., central venous catheter to ensure their ability to receive therapy without undue delay.

Neoadjuvant Treatment - Cabazitaxel

Julio Pow-Sang, M.D.

The aim of this study is to test whether adding chemotherapy/cabazitaxel and hormonal/androgen deprivation therapy before surgical removal of your prostate would improve the outcome of salvage surgery for locally recurrent prostate cancer after the initial primary radiation therapy.

In this study, all participants will receive cabazitaxel chemotherapy, which is approved as a second line chemotherapy for treating metastatic prostate cancer. Standard hormone or androgen ablation therapy will also be used as part of the chemohormonal therapy prior to the surgery.

Neoadjuvant Chemohormonal Therapy Followed by Salvage Surgery for High Risk PSA

Neoadjuvant Chemohormonal Therapy Followed by Salvage Surgery for High Risk PSA Failure With Biopsy Proven Local Recurrence After Initial Definitive Radiotherapy

Post surgery percentage of participants with negative surgical margin. To determine the surgical margin negative rate in patients who have undergone chemohormonal therapy followed by surgery for biopsy proven androgen-dependent high risk locally recurrent prostate cancer following primary radiation therapy. Margin: The edge or border of the tissue removed in cancer surgery. The margin is described as negative or clean when the pathologist finds no cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. The margin is described as positive or involved when the pathologist finds cancer cells at the edge of the tissue, suggesting that all of the cancer has not been removed.

Percentage of participants with stable (has not increased) or undetectable PSA post surgery. To assess Prostate-specific antigen(PSA)-progression free survival and prostate cancer specific survival for patients treated by chemohormonal therapy followed by salvage surgery for biopsy proven androgen-dependent high-risk locally recurrent prostate cancer following radiation therapy.

Percentage of participants with CR post surgery. To evaluate the pathological complete response rate to androgen ablation plus Cabazitaxel in patients with locally recurrent prostate cancer following radiation therapy. Pathological Complete Response (pCR): Participants with no residual cancer in the local resection specimen and pelvic lymph nodes will be considered pCR.

Number of events. To access the perioperative and postoperative morbidity with salvage surgery after neoadjuvant hormonal ablation and Cabazitaxel.

To determine the feasibility of detecting circulating tumor cells in this patient population. CTC results per patient in milliliters.

Sanofi

H. Lee Moffitt Cancer Center and Research Institute

Experimental: Drug and Hormonal Therapy With Salvage Surgery

Age, Continuous

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Study was closed early due to low accrual. Investigators had planned to follow 25 participants from On Study through End of Follow-up, up to 10 years.

Surgical Margin Negative Rate (SM Rate)

Incidence of PSA Progression Free Survival (PFS)

Incidence of Complete Response (CR)

Incidence of Perioperative and Postoperative Morbidity

Baseline CTC/mL

1 Month CTC/mL

3 Month CTC/mL

Baseline CTC Clusters/mL

1 Month CTC Clusters/mL

3 Month CTC Clusters/mL

Baseline Apop/mL

1 Month Apop/mL

3 Month Apop/mL

Baseline Small Cells/mL

1 Month Small Cells/mL

3 Month Small Cells/mL

Baseline CK-CTC/mL

1 Month CK-CTC/mL

3 Month CK-CTC/mL

Participant One

Participant Two

Incidence of Detecting Circulating Tumor Cells (CTC)

Overall Study

Disease Progression

Vaccines

Immunologic Factors

3 months of androgen ablation followed at PSA progression by 3 months of the combination of androgen ablation + DC1 vaccine

AA: Lupron 22.5 mg or Zoladex 10.8 mg DC vaccine: intradermal (id) vaccine of 3-5 x 10e6 cells

3 months of the combination of androgen ablation + DC1 vaccine followed at PSA progression by 3 months of androgen ablation

AA: Lupron 22.5 mg or Zoladex 10.8 mg DC vaccine: intradermal (id) vaccine of 3-5 x 10e6 cells

androgen ablation (AA)

DC1 vaccine

Leonard J Appleman, MD, PhD

This study will evaluate the feasibility, safety, and efficacy of intradermal vaccination of prostate cancer patients with alpha-type-1-polarized dendritic cells (DC1) loaded with apoptotic allogeneic tumor (LNCap). The study will target men with recurrent prostate cancer, who failed local therapy, have no measurable metastasis, but have a rising PSA with a doubling time of less than 10 months. The selection of this study group enables us to evaluate time to PSA progression, a highly relevant, clinical primary endpoint of efficacy in this two arm study. In order to facilitate infiltration of vaccination-induced T cells into tumor site(s) and to reduce tumor-specific tolerance, subjects will receive the vaccine in combination with limited androgen ablation (AA) with a LHRH analogue for 3 months. Subjects will be randomly assigned to one of two cohorts. In cohort A subjects will be first treated with limited AA alone for 3 months, and at the time of PSA relapse (PSA ≥ 1 ng/dL) will receive the DC vaccine in conjunction with AA. In cohort B, the sequence of treatment will be reversed. Efficacy will be estimated as the within-subject difference in time to PSA relapse following the combination treatment as compared to the AA alone, thus, each subject will serve as his own control. All subjects will commence the DC1-based vaccination 2 weeks prior to treatment with the LHRH analogue. Each subject will receive 1 intradermal (i.d.) dose of the vaccine at weeks 1, 5, 9, and 13 for a total of 4 doses. Additional courses of vaccination may be administered to subjects without evidence of disease progression every 3 months (±1 month) for up to 12 months depending on the number of doses originally produced and available after the 4 intended protocol doses. All doses of the vaccine will be administered intradermally (i.d.).

Dendritic cells or "DCs" are special white blood cells that stimulate the immune system. This study is being done to test the feasibility, safety and efficacy of a specific type of dendritic cell when injected under the skin of patients with prostate cancer. The researchers conducting this study will evaluate the time to prostate specific antigen (PSA) progression and will also be performing tests to see how the immune system is responding to the injections.

This is a 2 group crossover trial in which patients are randomly assigned to one of two treatment arms:

A. 3 months of androgen ablation (AA) to be followed at PSA progression by 3 months of the combination of AA and alpha-type 1 dendritic cell vaccine (DC1); B. 3 months of the combination of AA and alpha-type 1 dendritic cell vaccine followed at PSA progression by 3 months of AA.

Primary Objectives

* Feasibility objective: the ability to successfully generate and administer the alpha-DC1 vaccine.
* Safety objective: assess the tolerability and toxicity of the alpha-DC1 vaccine.
* Efficacy objective: evaluate the effect of the alpha-DC1 vaccine on time to PSA progression compared to AA alone. PSA progression is defined as a rise in the PSA value to e 1.0 ng/mL.

Secondary Objectives

* To determine the change in PSA velocity prior to and following the proposed treatment.
* To evaluate (in all subjects) the vaccination-induced DTH responses to LNCap, the cell line vaccine, and to compare this with vaccination-induced responses to tumor-untreated antigen (KLH).
* To evaluate the vaccination-induced changes of Th1/Th2 profiles of the responses to PAP and PSMA.
* To evaluate the CTL responses in blood to the whole LNCap cells (in all subjects) and (in all subjects who are HLA-A2 positive) the CTL responses to HLA-A2.1 restricted peptides derived from PAP and PSMA.
* To comprehensively evaluate the CD4+ and CD8+ T cell responses (fine specificity and Th1/Th2/Treg cytokine profile) to the previously-identified and novel immunogenic epitopes of PAP and PSMA, using the EPIMAX system.

This is a 2 group crossover trial in which patients are randomly assigned to one of two treatment arms:

A. 3 months of androgen ablation (AA) to be followed at PSA progression by 3 months of the combination of AA and alpha-type 1 dendritic cell vaccine (DC1); B. 3 months of the combination of AA and alpha-type 1 dendritic cell vaccine followed at PSA progression by 3 months of AA.

In this crossover trial each patient will serve as their own control. Following either therapy the time to PSA progression, defined as the time between treatment and the first instance of PSA increase to 1ng/ml. The endpoint is the difference between time to PSA progression for the combination of AA + DC1 compared to AA alone. A total of 12 evaluable patients (6 patients/arm) will be enrolled on the trial. Patients who do not complete both courses (AA and AA+DCV) will be replaced. This schema will also help us better estimate the time to PSA recovery following 3 months of limited androgen ablation in our cohort of patients.

All patients in Cohort B, will commence DC1-based vaccination 2 weeks prior to treatment with the LHRH analogue. Each patient will receive four i.d. doses of the vaccine at weeks 1, 4, 8, and 12. The LHRH analogue (Lupron 22.5 mg or Zoladex 10.8 mg), will be administered 2 weeks after the 1st dose of the DC vaccine. Additional courses of vaccination can be administered to any patients without evidence of disease progression, every 3 months for up to 12 months.

Patients will undergo a thorough pre-study evaluation, and then undergo leukapheresis to generate the DC-based vaccine. Each patient will receive 4 doses of intradermal (i.d.) DC1-based vaccine at weeks 1, 4, 8, and 12.

Dendritic Cell (DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With Prostate Cancer

Feasibility, Safety and Efficacy Evaluation of Alpha-Type 1 Dendritic Cell(DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With PSA Progression After Local Therapy for Prostate Cancer

The percentage of patients for which the alpha-DC1 vaccine was generated and for which 4 vaccine injections were administered (1 injection every 4 weeks).

The percentage of patients who experienced vaccine related toxicity.

The mean difference between time to relapse on androgen ablation plus alpha DC-1 vaccine vs androgen ablation

University of Pittsburgh

Roswell Park Cancer Institute

3 months of androgen ablation followed at PSA progression by 3 months of the combination of androgen ablation + DC1 vaccine

AA: Lupron 22.5 mg or Zoladex 10.8 mg DC vaccine: intradermal (id) vaccine of 3-5 x 10e6 cells

androgen ablation (AA): Lupron 22.5 mg or Zoladex 10.8 mg

DC1 vaccine: 3-5 x 10e6 cells total

Cohort A

3 months of the combination of androgen ablation + DC1 vaccine followed at PSA progression by 3 months of androgen ablation

AA: Lupron 22.5 mg or Zoladex 10.8 mg DC vaccine: intradermal (id) vaccine of 3-5 x 10e6 cells

androgen ablation (AA): Lupron 22.5 mg or Zoladex 10.8 mg

DC1 vaccine: 3-5 x 10e6 cells total

Cohort B

Total

Race (NIH/OMB)

Despite numerous attempts to obtain required data from the previous IND holder where the data is housed, including attempts to contact study PI and team, no responses were obtained and no data were available for this some Outcome Measures.

Senior Administrator, Compliance - Clinical Research Services

Percentage of Patients to Successfully Generate and Administer the Alpha-DC1 Vaccine

Tolerability and Toxicity of the Alpha-DC1 Vaccine

Despite numerous attempts to obtain required data from the previous IND holder where the data is housed, including attempts to contact study PI and team, no responses were obtained and no data are available for this Outcome Measure.

The Effect of the DC1 Vaccine on Time to PSA Progression Compared to AA Alone

The IND holder where the data is housed has stated that the data for this outcome was not collected.

Change in PSA Velocity Prior to and Following the Proposed Treatment.

Evaluate (in All Subjects) the Vaccination-induced DTH Responses to LNCap, the Cell Line Vaccine, and to Compare This With Vaccination-induced Responses to Tumor-untreated Antigen (KLH)

Evaluate the Vaccination-induced Changes of Th1/Th2 Profiles of the Responses to PAP and PSMA

Evaluate the CTL Responses in Blood to the Whole LNCap Cells (in All Subjects) and (in All Subjects Who Are HLA-A2 Positive) the CTL Responses to HLA-A2.1 Restricted Peptides Derived From PAP and PSMA

Comprehensively Evaluate the CD4+ and CD8+ T Cell Responses (Fine Specificity and Th1/Th2/Treg Cytokine Profile) to the Previously-identified and Novel Immunogenic Epitopes of PAP and PSMA, Using the EPIMAX System

Adenocarcinoma

Patients receive Cabozantinib at starting dose of 60 mg by mouth every day. Study cycles 3 weeks in duration. Patients stay on treatment as long as they are benefitting. Patients receive androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration. Study doctor will decide what hormone therapy patient will receive.

Starting dose of 60 mg by mouth every day of a 21 day cycle.

Cabozantinib

Androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration given upon decision of study doctor.

Androgen Ablation Therapy

Paul Corn, MD, PHD

The goal of this clinical research study is learn if adding cabozantinib (also known as XL184) to hormonal therapy can help to control prostate cancer. The safety of this drug will also be studied.

Cabozantinib is designed to block certain proteins in your blood that cause cancer cells to grow. This may cause cancer cells to die.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take 1 capsule of cabozantinib by mouth 1 time every day while you are on study. You should not eat or drink anything other than water for 2 hours before and 1 hour after taking the study drug. You should take the capsule with at least 1 cup (8 ounces) of water. You will also be given separate directions about how to take the study drug.

You will also receive hormone therapy. The hormone drug you receive will be standard of care hormone therapy. The study doctor will decide what hormone therapy you will receive and will explain when and how you should take the hormone therapy, as well as its risks.

You will be given a drug diary where you will record when you take cabozantinib. You should return this diary to the study staff when you come into the clinic.

Study Visits:

At every visit, you will be asked about any side effects you may have had and any other drugs you may be taking.

If you are receiving Coumadin, every week for the first 3 weeks, you will have blood drawn (about 1 teaspoon) to test your blood clotting function.

Every 3 weeks for the first 12 weeks of the study, and then every 6 weeks after that:

* You will have a physical exam.
* Blood (about 3-4 teaspoons) will be drawn for routine tests.

Every 3 weeks for the first 12 weeks of the study, and then every 12 weeks after that, blood (about 1 teaspoon) will be drawn to check your thyroid and pancreatic function. The frequency of the testing may change if the study doctor thinks it is needed.

Every 6 weeks, you will have the following tests performed:

* Blood (about 2-3 teaspoons) will be drawn to measure your PSA levels and for biomarker testing.
* Urine will be collected for routine tests.
* You may have these test performed near your home if the study doctor thinks you are tolerating the treatment.

Every 12 weeks, you will have a bone scan and CT scans of the chest, abdomen, and pelvis to check the status of the disease.

Length of Study:

You may continue receiving the study drug for as long as the study doctor thinks it is in your best interest. You will be taken off study early if the disease gets worse, if you have intolerable side effects, or if your study doctor thinks it is in your best interest to stop.

Long-Term Follow-Up:

You will be contacted every 6 months after you stop taking the study drug to check on how you are feeling and the status of the disease. This will consist of a phone call, e-mail, or medical record review. If you are called, each call should last about 5 minutes.

This is an investigational study. Cabozantinib is FDA approved to treat patients with certain types of thyroid cancer. Its use in this study is investigational.

Up to 60 participants will take part in this study. All will be enrolled at MD Anderson.

Cabozantinib and Androgen Ablation in Patients With Androgen-Dependent Metastatic Prostate Cancer

An Observational Study of XL-184 Cabozantinib and Androgen Ablation in Patients With Androgen-Dependent Metastatic Prostate Cancer

Progression defined by any of the following: (a) radiographic progression (using RECIST 1.1 for visceral disease and PCWG2 for Bone Scans), (b) receive additional anti-cancer therapy, or (c) clinical progression resulting in stopping the treatment.

Number of instances of Serious Adverse Events and Other (Not Including Serious) Adverse Events. Adverse events were monitored for 30 days beyond the last day of treatment. These adverse events are documented. The adverse events are reported as Serious Adverse Events and Adverse Events. Serious Adverse Events are defined as adverse events in which the participant dies, is hospitalized, is disabled, or is exposed to the medicine while pregnant resulting in and birth defect. Adverse events evaluated for all treated participants using the NCI CTCAE version 4.3.

Exelixis

High Impact Clinical Research Support Program

M.D. Anderson Cancer Center

Patients receive Cabozantinib at starting dose of 60 mg by mouth every day. Study cycles 3 weeks in duration. Patients stay on treatment as long as they are benefitting. Patients receive androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration. Study doctor will decide what hormone therapy patient will receive.

Cabozantinib: Starting dose of 60 mg by mouth every day of a 21 day cycle.

Androgen Ablation Therapy: Androgen ablation therapy, either by means of luteinizing hormone-releasing hormone super-agonist (of any formulation), LHRH antagonist, or surgical castration given upon decision of study doctor.

Cabozantinib + Androgen Ablation Therapy

Ethnicity (NIH/OMB)

Grade 0

Grade 1

Grade 2

ECOG measure a participant's daily living abilities. All participants in this trial are grade 0, grade 1, or grade 2.

Grade 0: Fully active on all pre-disease performance without restriction Grade 1: light housework and office work. Restricted in physically strenuous activity Grade 2: Ambulatory and capable of self-care. Not able to carry out work that is light or sedentary.

Eastern Cooperative Oncology Group (ECOG) Performance Status

No Prior Treatment

Yes Prior Treatment

Prior Treatment of Primary Tumor

Gleason 6-7

Gleason 7 + 5

Gleason 8-10

Unknown Gleason Score

Gleason score grades prostate cancer based on the severity of the cancer The scores range from 2 -10. The higher the score the more severe the cancer. Gleason Score of 6 is the lowest cancer grade. In this trial, participants who have a traditional Gleason 7 score with an additional area in the prostate that meets Gleason 5 score were counted separately and labeled Gleason 7 + 5.

Gleason Score

PSA is produced by normal and cancerous prostate tissue. PSA levels are often elevated in men with prostate cancer.

Prostate Specific Antigen (PSA) Levels

Only 59 of the participants had bone specific Alkaline Phosphatase level as baseline

Bone Specific Alkaline Phosphatase Level

Bone Metastases

Bone Only

Bone metastases measures help define the extent on the prostate cancer in the participants. The first measure, Bone Metastases counted the number of participants with bone metastasis. The second measure, Bone Only, counted the number of patients who only had prostate cancer present in the bone.

Visceral Metastases measurement determined how many participants at baseline had prostate tumors in any of the organs of the body. This measurement did not include bone or lymph nodes.

Visceral Metastases

None

Lymph Nodes

Liver

Lung

Soft-Tissue Metastases

High

The volume of metastases was categorized as high or low. A high volume was defined as a participant who had 3 or more bone tumors and/or visceral tumors.

Volume of Metastases

Dr. Paul Corn, Chair Ad Interim, Genitourinary Medical Oncology

Progression Free Survival

Other (Not Including Serious) Adverse Events

Serious Adverse Events

Serious Adverse Events and Other (Not Including Serious) Adverse Events

Abiraterone Acetate

Glucocorticoids

Enzyme Inhibitors

Cytochrome P-450 Enzyme Inhibitors

Patients receive abiraterone acetate (1,000 mg daily) plus prednisone (5mg once daily) in combination with enzalutamide (160 mg daily) and LHRHa. Patients receive a LHRHa (monthly injection or three-month injection) for a maximum of 7 months before a prostatectomy is performed. Study doctor will decide what hormone therapy patient receives.

Patients receive abiraterone acetate (1,000 mg daily) plus prednisone (5mg once daily) and LHRHa. Patients receive a LHRHa (monthly injection or three-month injection) for a maximum of 7 months before a prostatectomy is performed. Study doctor will decide what hormone therapy patient receives.

1,000 mg by mouth daily for each 28 day cycle.

5 mg by mouth once daily for each 28 day cycle.

160 mg by mouth daily for each 28 day cycle.

Enzalutamide

Patients receive a LHRHa (monthly injection or three-month injection) for a maximum of 7 months before a prostatectomy is performed. Study doctor will decide what hormone therapy patient receives.

LHRHa

Christopher Logothetis, MD

The goal of this clinical research study is to learn if adding the combination of abiraterone acetate and prednisone with or without enzalutamide to hormonal therapy can help to control prostate cancer when given before surgery. The safety of the drug combination will also be studied.

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (like the roll of dice) to 1 of 2 groups. You will have a 2 out of 3 chance of being assigned to Group A and a 1 out of 3 chance of being assigned to Group B.

If you are in Group A, you will receive hormonal therapy (LHRH), abiraterone acetate, prednisone, and enzalutamide.

If you are in Group B, you will receive LHRH, abiraterone acetate, and prednisone.

Study Drug Administration:

The study doctor will decide what hormone therapy you will receive, will explain when and how you should take it, and explain any risks.

In addition, you will take 4 abiraterone acetate tablets by mouth each day (all at the same time) at least 1 hour before a meal or 2 hours after a meal. You will also take 1 tablet of prednisone by mouth 1 time each day to help lower the risk of side effects caused by abiraterone acetate.

If you are in Group A, you will also take 4 capsules of enzalutamide by mouth each day. You should take enzalutamide at about the same time every morning. Enzalutamide can be taken with or without food. If you miss a dose, you should NOT take another dose until the next day. You should tell the study doctor as soon as possible if you miss a dose.

About every 28-days is called a cycle. You should return all unused study drug and/or empty pill bottles at the end of each cycle.

Study Visits:

On Day 1 of Cycle 1:

* You will have a physical exam.
* Blood (about 3-4 tablespoons) will be drawn for routine tests and to check your prostatic specific antigen (PSA) level.

On Day 15 of Cycles 1, 2 and 3, blood (about 2 tablespoons) will be drawn to check your liver function. These tests may be done at your local doctor's office and the results faxed to MD Anderson.

On Day 1 of Cycles 2, 3, 4, 5 and 6:

* You will have a physical exam.
* Blood (about 3-4 tablespoons) will be drawn for routine tests. This blood will also be used to check your PSA level.

The testing on Cycles 2, 4 and 6 may be done at your local doctor's office and the results faxed to MD Anderson.

Within 14 days before surgery and at your End of Treatment Visit:

* You will have a physical exam.
* Blood (about 3-4 tablespoons) and urine will be collected for routine tests. This blood will also be used to check your PSA level, your blood sugar levels, and blood-clotting function. You will be asked to fast for at least 8 hours before these blood draws.
* You will have a chest x-ray or a CT scan of the chest.
* You will have an EKG to check your heart function.

Surgery:

After 6 cycles of study treatment, you will have surgery to remove your prostate. You will be asked to sign a separate consent form for this surgery, and the risks will be discussed with you. Your leftover prostate gland tissue from surgery will be collected and used for biomarker testing.

About 4 to 8 weeks after your surgery:

* You will have a physical exam.
* Blood (about 3-4 tablespoons) drawn for routine tests. This blood will also be used to check your PSA, testosterone, cholesterol, and blood sugar levels.

Length of Study:

You may receive the study drugs for about 6 months. You will be taken off study early if the disease gets worse, if you have intolerable side effects, or if your study doctor thinks it is in your best interest to stop, or of you are unable to follow study directions.

Your participation on the study will be over once you have completed the visits after surgery.

This is an investigational study. Abiraterone acetate is FDA approved in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel. Prednisone is FDA approved and commercially available as a corticosteroid. Enzalutamide is FDA approved and commercially available for the treatment of certain types of prostate cancer. Their combination with hormone therapy in patients with prostate cancer is investigational.

Up to 69 patients will be enrolled in this study. All will be enrolled at MD Anderson.

Abiraterone Acetate Plus LHRH Agonist and Abiraterone Acetate Plus LHRH Agonist and Enzalutamide

A Pre-Operative Study to Assess the Effects of Abiraterone Acetate Plus LHRH Agonist and Abiraterone Acetate Plus LHRH Agonist and Enzalutamide for Six Months for Prostate Cancer Patients at High-Risk for Recurrence

The proportion of participants with pathologic stage less than or equal to ypT2N0 will be descriptively summarized and compared between the two treatment arms. The proportion will be calculated as the number of patients with less than or equal to ypT2N0 in each treatment arm divided by the total number of patients who underwent surgery in the same arm.

The difference in the rate of positive surgical margins between the two groups will be descriptively summarized.

Janssen Services, LLC

Medivation, Inc.

Adverse events were collected and reported according to protocol requirements.

Patients receive abiraterone acetate (1,000 mg daily) plus prednisone (5mg once daily) in combination with enzalutamide (160 mg daily) and LHRHa. Patients receive a LHRHa (monthly injection or three-month injection) for a maximum of 7 months before a prostatectomy is performed. Study doctor will decide what hormone therapy patient receives.

Abiraterone Acetate: 1,000 mg by mouth daily for each 28 day cycle.

Prednisone: 5 mg by mouth once daily for each 28 day cycle.

Enzalutamide: 160 mg by mouth daily for each 28 day cycle.

LHRHa: Patients receive a LHRHa (monthly injection or three-month injection) for a maximum of 7 months before a prostatectomy is performed. Study doctor will decide what hormone therapy patient receives.

Arm A: Abiraterone + Enzalutamide + LHRHa + Prednisone

Patients receive abiraterone acetate (1,000 mg daily) plus prednisone (5mg once daily) and LHRHa. Patients receive a LHRHa (monthly injection or three-month injection) for a maximum of 7 months before a prostatectomy is performed. Study doctor will decide what hormone therapy patient receives.

Abiraterone Acetate: 1,000 mg by mouth daily for each 28 day cycle.

Prednisone: 5 mg by mouth once daily for each 28 day cycle.

LHRHa: Patients receive a LHRHa (monthly injection or three-month injection) for a maximum of 7 months before a prostatectomy is performed. Study doctor will decide what hormone therapy patient receives.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant Chemohormonal Therapy Followed by Salvage Surgery for High Risk PSA	NCT01531205	Prostate Cancer	Androgen Ablati... Cabazitaxel Salvage Therapy Neoadjuvant Tre... Neoadjuvant Tre...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Neoadjuvant Chemohormonal Therapy Followed by Salvage Surgery for High Risk PSA	NCT01531205	Prostate Cancer	Androgen Ablati... Cabazitaxel Salvage Therapy Neoadjuvant Tre... Neoadjuvant Tre...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Dendritic Cell (DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With Prostate Cancer	NCT00970203	Cancer of Prost... Cancer of the P... Neoplasms, Pros... Neoplasms, Pros... Prostate Cancer Prostate Neopla... Prostatic Cance...	androgen ablati... DC1 vaccine	18 Years -	Roswell Park Cancer Institute
Cabozantinib and Androgen Ablation in Patients With Androgen-Dependent Metastatic Prostate Cancer	NCT01630590	Prostate Cancer	Cabozantinib Androgen Ablati...	-	M.D. Anderson Cancer Center
Dendritic Cell (DC)-Based Vaccines Loaded With Allogeneic Prostate Cell Lines in Combination With Androgen Ablation in Patients With Prostate Cancer	NCT00970203	Cancer of Prost... Cancer of the P... Neoplasms, Pros... Neoplasms, Pros... Prostate Cancer Prostate Neopla... Prostatic Cance...	androgen ablati... DC1 vaccine	18 Years -	Roswell Park Cancer Institute
Cabozantinib and Androgen Ablation in Patients With Androgen-Dependent Metastatic Prostate Cancer	NCT01630590	Prostate Cancer	Cabozantinib Androgen Ablati...	-	M.D. Anderson Cancer Center
Abiraterone Acetate Plus LHRH Agonist and Abiraterone Acetate Plus LHRH Agonist and Enzalutamide	NCT01946165	Prostate Cancer	Abiraterone Ace... Prednisone Enzalutamide LHRHa	18 Years -	M.D. Anderson Cancer Center
Feasibility and Toxicity of Degarelix for Prostate Downsizing Prior to Permanent Seed Prostate Brachytherapy	NCT01446991	Prostate Cancer	Degarelix Degarelix	40 Years - 80 Years	British Columbia Cancer Agency

Spots Global Cancer Trial Database for androgen ablation