The goal of this clinical research study is to learn if ipilimumab in combination with either Lupron® (leuprolide), Zoladex® (goserelin), or Firmagon® (degarelix) can affect prostate-specific antigen (PSA) levels in patients with prostate cancer. Researchers also want to learn if these drug combinations affect the body's immune system. The safety of these drug combinations will also be studied.
The Study Drugs: Ipilimumab is designed to block the activity of cells that decrease the immune system's ability to fight cancer. Leuprolide, goserelin, and degarelix are designed to help stop the body from making testosterone (a male sex hormone that prostate cancer cells need to survive), which 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 either leuprolide, goserelin or degarelix . The drug you receive will depend on what the doctor thinks is in your best interest and/or which drug your insurance provider will help to cover. Leuprolide is given through a needle in the muscle. Goserelin and degarelix are given through a needle under the skin in the abdomen. Beginning at Week 1, you will receive the drug 1 time every month or every 3 months for up to 8 months. Your doctor will tell you more about which dosing schedule you will use. You will also receive ipilimumab by vein over about 90 minutes at Weeks 5, 9, 13, and 17. Your blood pressure will be measured every 30 minutes during the infusion, as well as an hour after you are finished receiving the drug. Study Visits: Before each dose of ipilimumab, and every 4 weeks for 6 months after the last dose of ipilimumab, and every 12 weeks after that, the following tests and procedures will be performed: * You will have a physical exam. * You will be asked about any other drugs and/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 3 teaspoons) will be drawn for routine tests and to measure your protein, PSA, and testosterone levels, and to check the function of your pancreas, thyroid, and adrenal glands. * Urine will be collected for routine tests. * This blood will also be tested for other hormone levels to check the function of your thyroid and adrenal glands (before each dose of ipilimumab and 4 weeks after the last dose only). Every 12 weeks, you will have the same imaging scans that you had at screening. Length of Study: You may receive the study drugs for up to 8 months. You will remain on study for as long as the disease remains stable. You will be taken off study treatment if you have intolerable side effects or if the disease gets worse. End-of-Study Treatment/Observation Visit: Within 14 days after your disease gets worse, the following tests and procedures will be performed: * You will have a physical exam. * You will be asked about any drugs and/or treatments you may be receiving. * You will be asked about any side effects you may have experienced. * Blood (about 3 teaspoons) will be drawn for routine tests. This blood will also be tested to measure your protein, PSA, and testosterone levels, and to check the function of your pancreas, thyroid, and adrenal glands. * You will have the same imaging scans that you had at screening. Long-Term Follow-Up: A member of the study staff will check up on you about every 6 months after your End-of-Study Treatment/Observation Visit. This will consist of a phone call, an e-mail, or a review of your medical and/or other records. If you are contacted by phone, the call will only last a few minutes. This is an investigational study. Leuprolide, goserelin, and degarelix are FDA approved and commercially available for the treatment of prostate cancer. Ipilimumab is FDA approved and commercially available for melanoma. Its use to treat prostate cancer is investigational. Up to 48 patients will take part in this study. All will be enrolled at MD Anderson.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
10 mg/kg by vein over 90 minutes once every 4 weeks, for 4 weeks.
7.5 mg intramuscular once a month for 8 months
3.6 mg subcutaneous once a month for 8 months
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Number of Participants Who Progressed After 7 Months of Being on Treatment
Anti-tumor activity assessed through serial PSA measurements (blood tests) at 7 months on treatment. Progression defined as two consecutive PSA values increasing by at least 20% or more from the lowest PSA value for each patient.
Time frame: at the end of 7 months on treatment
The Number of Clonal Expansion of Cluster of Differentiation 8 (CD8) T-cells
CD8 T-cells are known as cytotoxic T-cells or "killer" T-cells. When the resting CD8 T-cells are activated, the activated CD8 T-cells multiple to fight a specific target so creating a group of specifically activated T-cells. This test measured the minimal number of clonal expansions of CD8 T-cells that always preceded an adverse response to treatment that was due to increased activity in the immune system itself. The minimal number of clonal expansion points to what this increased activity in the immune system might look like.
Time frame: Each evaluable patient was followed from the time of their first dose until 30 days after their last dose of study drug
Time to Testosterone Recovery (> 50ng/mL) in Patients Treated With Intermittent ADT Plus Ipilimumab.
The presence of testosterone was followed in each patient from the start of treatment until the testosterone lab test was found to be at a value greater than 50ng/mL.
Time frame: 1 month up to 7 months.
Time to Progression of Disease (PD) Off Androgen Depravation Therapy (ADT), After Treatment With Intermittent ADT Plus Ipilimumab.
The number of months after the last ADT dose until the PSA progression
Time frame: 2 to 45 months
The Total Number of Study Drug Related Events Indicated by the Participants
The total number of adverse events which were related to one of the study drugs. Grade 1- Mild, asymptomatic of mild symptoms; clinical or diagnostic observation only; intervention not indicated. Grade 2- Moderate, minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental (daily living activities). Grate 3- Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care of daily life activities.
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80 mg subcutaneous once a month for 8 months
Time frame: From the first dose to the last follow-up, up to 60 months
Overall Survival
Overall survival of patients treated with intermittent ADT and ipilimumab in months.
Time frame: From the date of randomization until the date of first documented progression or date of death from any case, whichever came first, assessed up to 70 months.