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

Reproductive Control Agents

Hormones

Angiogenesis Inhibitors

Leuprolide

Sunitinib

Goserelin

Bicalutamide

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Hormonal

Androgens

Androgen Antagonists

Hormone Antagonists

Sunitinib Malate + Hormone Ablation (Leuprolide or Goserelin + Bicalutamide) + Radiation Therapy (RT)

Injections given through a needle in the muscle every 3 months.

Subcutaneous injections given once every 3 months.

Starting dose of 12.5 mg by mouth daily for 4 weeks

Sunitinib Malate

Casodex

Radiation treatment once daily over a period of 8 weeks.

Radiation Therapy (RT)

Paul Corn, MD, PHD

The goal of this clinical research study is to learn the safety of adding 3 different dose-levels of Sutent® (sunitinib malate) to a combination of hormone therapy and radiation in patients with prostate cancer.

The Study Drugs:

Sunitinib malate is designed to block pathways that control important events such as the growth of blood vessels that are essential for the growth of cancer.

Luteinizing Hormone-Releasing Hormone (LHRH) Analogues like Lupron® (leuprolide) and Zoladex® (goserelin) are hormonal treatments used to help stop the body from making testosterone (male sex hormones) in the body. Prostate cancer cells need testosterone to survive.

Anti-Androgen drugs, like Casodex® (bicalutamide) also stop cell growth by blocking male hormones like testosterone.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will be assigned to a study group. The group you are assigned to and dose of sunitinib malate you receive will depend on when you join this study. Three (3) dose levels of sunitinib malate will be tested. The first group of participants will receive the lowest dose of sunitinib malate. The next group enrolled will receive a higher dose of sunitinib malate, if no intolerable side effects were seen.

Before you begin taking sunitinib, you will begin receiving hormone therapy. You will receive leuprolide or goserelin. Leuprolide is given through a needle in your muscle, and goserelin is given through a needle under the skin in the abdomen. You will receive 1 of these injections every 3 months. Which hormonal drug you are given (leuprolide or goserelin) will be assigned by your doctor and/or will depend on your insurance coverage.

You may also receive bicalutamide. This will be left up to the doctor. You will take bicalutamide by mouth once a day for 2 weeks (with or without food).

After at least 4 weeks of hormone therapy have been given, you will begin taking sunitinib malate in combination with the hormone therapy. You will take sunitinib malate once a day (either with or without food) for 16 weeks in a row.

Radiation Therapy:

After 4 weeks of combined treatment with sunitinib and hormone therapy, you will begin radiation treatments. Radiation treatments will be given once a day, 5 days a week, for about 8 weeks. Each treatment will take 20-30 minutes. This procedure will be discussed with you in more detail. You will continue taking sunitinib and hormone therapy while you are on radiation treatments.

Study Visits:

On the day you start treatment with sunitinib, you will have the following tests and procedures performed:

* You will have a physical exam, including measurements of your blood pressure and weight.
* You will be asked about any side effects you may have had since your last visit.
* Blood (about 1 teaspoon) will be drawn for routine tests.

About Day 15 of treatment with sunitinib, and on the day you begin radiation therapy (before your first treatment), you will have the following tests and procedures performed:

* You will have a physical exam, including measurements of your blood pressure and weight.
* You will be asked about any side effects you may have had since your last visit.
* Blood (about 2 teaspoons) will be drawn for routine tests.

Every 2 weeks during radiation therapy, you will have the following tests and procedures performed:

* You will have a physical exam, including measurements of your blood pressure and weight (every 2 weeks)
* You will have blood drawn (about 2 teaspoons) for routine testing.
* You will be asked about any side effects you may have had since your last visit.

About 4 weeks after you stop radiation therapy, you will have the following test and procedures performed:

* You will have a physical exam, including measurements of your blood pressure and weight.
* Blood (about 2 teaspoons) and urine will be collected for routine tests. The blood testing will include measurement of prostatic specific antigen (PSA) and testosterone levels.
* You will be asked about any side effects you have had since your last visit.

Length of Study:

You will continue taking sunitinib malate on this study for a total of 16 weeks. Radiation treatments will last for up to 8 weeks. Hormone injections will continue for a period of 2 years. You will be taken off this study if intolerable side effects occur or the disease gets worse.

Long-Term Follow-up:

You will be followed every 6 months via telephone call and/or a review of your medical record. If contacted, you will be asked about any side effects you have had, or therapies you may have had since stopping treatment on this study. You will be followed for up to 10 years once you have taken sunitinib malate for 20 weeks.

This is an investigational study. Sunitinib malate is FDA approved and commercially available for the treatment of adults with kidney cancer.

Bicalutamide, leuprolide, and goserelin are FDA approved and commercially available for use in prostate cancer.

Up to 22 patients will be enrolled in this multicenter trial. Up to 12 will be enrolled at MD Anderson.

Sunitinib Malate, Hormone Ablation and Radiation Therapy in Patients With Prostate Cancer

Sunitinib, Hormonal Ablation and External Beam Radiation Therapy for High-Risk and Locally Advanced Prostate Cancer

DLT defined as inability to complete the schedule course of radiation therapy for toxicity of any grade. If \< 2 patients in initial cohort of 6 experience DLT then a subsequent dose-level cohort initiated. If 2 or more patients in a cohort experience DLT then further accrual to that cohort curtailed and no higher dose level examined. Maximum tolerated dose (MTD) for oral sunitinib in combination with radiation and hormone ablation defined as highest dose level in which 6 patients have been treated with 2 or less than 2 instances of DLT.

DLT for the purposes of dose-escalation or calculation of the maximum tolerated dose (MTD) defined as any medically unmanageable Grade 2 toxicity or any Grade 3 or 4 toxicity experienced during the 8 week period of combined hormone ablation, Sunitinib, and radiation therapy.

Pfizer

M.D. Anderson Cancer Center

Adenocarcinoma

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Leuprolide Acetate 22.5 mg administered as a single intramuscular 3 month depot + Ipilimumab 10 mg/kg by vein administered as 2 single doses, 3 weeks apart after hormone therapy + Radical Prostatectomy Surgery to remove prostate gland approximately 4 weeks after the second dose of Ipilimumab.

22.5 mg administered as a single intramuscular 3 month depot.

Leuprolide Acetate

10 mg/kg by vein administered as 2 single doses, 3 weeks apart after hormone therapy.

Surgery to remove prostate gland approximately 4 weeks after the second dose of Ipilimumab.

Radical Prostatectomy

Padmanee Sharma, MD, PHD

The goal of this clinical research study is to learn how ipilimumab in combination with Lupron (leuprolide acetate) affects the body's own defense (immune) system before having surgery to remove prostate cancer. The safety of the drug combination will also be studied.

The Study Drugs:

Ipilimumab is designed to cause an immune response in your body by blocking 2 specific molecules that usually block an immune response. This may help to kill cancer cells.

Leuprolide acetate is designed to lower the level of testosterone (a male hormone) in the blood. This may slow the growth of cancer cells.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will receive a leuprolide acetate injection in your muscle. This is considered Week 0. One week later, you will begin treatment with ipilimumab. Ipilimumab will be given by vein over 90 minutes during Weeks 1 and 4 (about 21 days apart). During the infusion, your blood pressure will be measured every 30 minutes, and again an hour after you are finished receiving the drug.

Study Visits:

At Weeks 0, 1, 4 and 7, the following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs and weight.
* You will be asked about any drugs or treatments you may be receiving.
* You will be asked about any side effects you may have experienced.
* Your performance status will be recorded.
* Blood (about 7-10 tablespoons) will be drawn for routine tests. This blood will also be tested to measure your protein, PSA and testosterone levels, to check the function of your thyroid and adrenal glands, and to test for an immune response.

Surgery:

About 4 weeks after your second treatment with ipilimumab, you will have surgery to remove your prostate gland. You will be asked to sign a separate consent form that describes the surgery and its risks. A sample of the leftover prostate gland tissue from surgery will be tested for an immune response. On that day, the following tests and procedures will be performed:

Between 14 and 24 weeks after your surgery, you will return to the clinic for your post-operative follow-up visit. The following tests and procedures will be performed:

* You will have a physical exam, including measurement of your vital signs and weight.
* Your performance status will be recorded.
* You will be asked about any drugs or treatments you may be receiving.
* You will be asked about any side effects you have experienced since your last visit.
* Blood (about 7-10 tablespoons) will be drawn for routine tests. This blood will also be used to measure your protein, testosterone and PSA levels, to check the function of your thyroid and adrenal glands, and to test for an immune response.
* You will have a bone scan, and either a CT or MRI scan of your chest, abdomen, and pelvis to check the status of the disease.

Length of Study:

You will only receive 2 treatments with ipilimumab on this study. You will be on study until 24 weeks after surgery. You will be taken off study if intolerable side effects occur, if the disease gets worse, or if the study doctor thinks it is in your best interest to be taken off study.

This is an investigational study. Ipilimumab is not FDA approved or commercially available. Ipilimumab is currently being used for research purposes only. Leuprolide acetate is FDA approved for management of metastatic prostate cancer but is not approved for use before definitive surgery. It is commercially available to treat prostate cancer.

Up to 20 patients will take part in this study. All will be enrolled at MD Anderson.

Neoadjuvant Ipilimumab in Prostate Cancer

A Neoadjuvant Phase IIa Study of Ipilimumab {Formerly Known as MDX-010 (BMS-734016)} Plus Hormone Ablation in Men With Prostate Cancer Followed by Radical Prostatectomy.

Immunological response assays were measured at several time points starting at baseline until the eighth week after starting the medicine for each participant. The immunological responses measured were Cluster of Differentiation 4 (CD4), Cluster of Differentiation 8 (CD8) and Inducible T-cell Costimulatory (ICOS) markers. T-cells with the CD4 marker help coordinate the immune system response to an invader. Killer T-cells have the CD8 marker and are responsible for killing the invader. ICOS is a molecule which stimulates the activity of the immune response of the killer T-Cells and memory T cells. Participants with at least a 2 fold increase in the presence of CD4, CD8, or ICOS markers from the participant's baseline measure were considered a responder for that marker.

Bristol-Myers Squibb

Two participants of nineteen registered on the study were excluded prior to any treatment assignment due to screen failure and withdrawal, therefore are not included in adverse event reporting.

Neoadjuvant Ipilimumab

Age, Continuous

Sex: Female, Male

White

Black

Race/Ethnicity, Customized

United States

Region of Enrollment

Prostate-specific antigen (PSA) 4 categories for describing the local extent of a prostate tumor, ranging from T1 to T4

PSA (Average) Tumor Clinical Stage

Gleason Score

One dose

Two doses

Lupron Ipilimumab Dose

Surgery

Two participants are not included in the demographics, excluded from the study due to screening failure or withdraw prior to being assigned any treatment.

Padmanee Sharma, Professor, Genitourinary Medical Oncology

ICOS

One participant was not evaluable for outcome due to early death. Of evaluable 16 participants, the number of participants (N) analyzed reflected in CD4, CD8 and ICOS that are associated with immune response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Sunitinib Malate, Hormone Ablation and Radiation Therapy in Patients With Prostate Cancer	NCT00631527	Prostate Cancer	Leuprolide Goserelin Sunitinib Malat... Casodex Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Neoadjuvant Ipilimumab in Prostate Cancer	NCT01194271	Prostate Cancer	Leuprolide Acet... Ipilimumab Radical Prostat...	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for hormone ablation