Prostate Adenocarcinoma, Prostate Carcinoma, Recurrent Prostate Carcinoma, Stage III Prostate Cancer, Stage IV Prostate Cancer
Conditions
Brief summary
RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide acetate, goserelin, flutamide, or bicalutamide may lessen the amount of androgens made by the body. Monoclonal antibodies, such as ipilimumab, can block cancer growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Giving antihormone therapy together with ipilimumab may kill more tumor cells. PURPOSE: This randomized phase II trial is study how well giving hormone therapy and ipilimumab together works in treating patients with advanced prostate cancer.
Detailed description
OBJECTIVES: I. To generally test whether the addition of CTLA-4 blockade can enhance clinical treatment response in advance prostate cancer patients compared with treatment with AA therapy alone. II. To specifically examine whether concomitant AA therapy + MDX-010 can be used to prolong the progression-free interval in advanced prostate cancer patients compared with inductive short-term AA therapy alone. III. To specifically examine whether concomitant AA therapy + MDX-010 can be used to enhance initial PSA responses in advanced prostate cancer patients compared with inductive short-term AA therapy alone. IV. To specifically examine whether delayed MDX-010 can be used to induce PSA response in patients experiencing disease progression following cessation of short-term AA therapy. V. To generally examine whether MDX-010 enhances host immune response that might be involved in conferring treatment advantages to patients receiving AA therapy. VI. To specifically examine whether MDX-010 potentiates T-cell responses in advanced prostate cancer patients initiating inductive short-term AA therapy. VII. To further examine whether treatment induced T-cell responses correlate with clinical response to treatment. VIII. To examine whether short-term AA there (+/- MDX-010) induces the appearance of newly emigrated T or immature and/or B cells. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive either leuprolide acetate intramuscularly (IM) or goserelin subcutaneously (SC) on days 0, 28, and 56. Patients also receive oral flutamide three times daily or oral bicalutamide once daily. Treatment with antiandrogen (AA) therapy continues for 3 months (3-4 months for patients who initiated AA therapy \<= 21 days prior to enrollment) in the absence of disease progression or unacceptable toxicity. Patients receive ipilimumab IV over 90 minutes on day 7 (within 7-28 days post-initiation of AA therapy for patients who initiated AA therapy \<= 21 days prior to enrollment) of AA therapy. Arm II: Patients receive AA therapy as in arm I. Patients may crossover to arm II in the case of disease progression. After completion of study treatment, patients are followed periodically.
Interventions
DRUGBicalutamide
Given orally
DRUGFlutamide
Given orally
DRUGGoserelin Acetate
Given SC
DRUGIpilimumab
Given IV
DRUGLeuprolide Acetate
Given IM
OTHERPharmacological Study
Correlative study
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* NOTE: All values must be obtained =\< 14 prior to study entry * Histologically confirmed adenocarcinoma of the prostate staged within 180 days of study enrollment, \>cT2cN0/M0 stage with or without metastatic disease, with the exclusion of central nervous system (CNS) metastases; includes post radical prostatectomy patients with a rising PSA * An initial PSA \>= 4.0 ng/mL (Hybritech Assay) * For those patients who have received hormone therapy =\< 21 days, a documented PSA of \>= 4.0 prior to initiation of hormone therapy is acceptable. * For patients who are post radical prostatectomy, a rising PSA is acceptable. * Adequate organ function defined as: WBC \>= 3,000/uL; platelets \>= 75,000/uL; total bilirubin =\< 1.5 mg/dL; transaminases =\< 2.5 x upper limit of normal (ULN); serum creatine =\< 2.0 mg/dL or calculated creatinine clearance \>= 60 mL/min * ECOG performance status of 0-2 * Able to understand and sign informed consent
Exclusion criteria
* Underlying other serious medical condition which, in the opinion of the investigator precludes study participation; this includes immune-suppressive disease such as AIDS or autoimmune disorders such as multiple sclerosis, lupus, or myasthenia gravis * Patients not recovered from major infections and/or surgical procedures * Prior hormonal therapy \> 21 days prior to enrollment, including estrogens, LH/RH agonists, or antiandrogens * Recent (=\< 3 months of informed consent) usage of immune-suppressive medication including steroids, Immuran, Cyclosporin; topical or inhalational steroid use is permissible * Prior systemic chemotherapy * Prior radiation therapy to the prostate * Prior malignancy, unless the patient has been cancer-free for five years or more * Uncontrolled underlying medical or psychiatric illness, or serious active infections * Patient unwilling to complete all required follow-up visits * History of motor neuropathy considered of the autoimmune origin (e.g. Guillian-Barre Syndrome) * Concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer * For patients who elect to undergo the baseline transrectal needle biopsy of the prostate, current usage of systemic anticoagulation therapy, i.e. heparin or Coumadin or inability to discontinue aspirin, aspirin-containing products or ibuprofen for seven days prior to the prostate biopsies required for this study * No other investigational drugs will be allowed during the study * Other chemotherapy, radiation therapy, immunotherapy, hormonal therapy, or biologic therapy may not be used while the patient is on study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Progression-free at 18 Months | 18 months from the start of AA therapy | PSA progression is defined as a rise in PSA to \>4.0 ng/mL demonstrated twice in measurements taken two weeks apart. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Undetectable Prostate-specific Antigen (PSA) Response | 3 months | Percent of participants who had undetectable PSA at 3 months on the initially assigned treatment arm (prior to crossing over). |
Countries
United States
Participant flow
Recruitment details
112 participants were recruited between June 2004 and June 2009 at Mayo Clinic.
Pre-assignment details
All participants were initially randomized to either arm.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population All participants initially randomized. | 112 |
| Total | 112 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Customized <= 39 | 0 participants |
| Age, Customized 40-49 | 5 participants |
| Age, Customized 50-59 | 29 participants |
| Age, Customized 60-69 | 48 participants |
| Age, Customized >= 70 | 30 participants |
| Region of Enrollment United States | 112 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 107 / 110 |
| serious Total, serious adverse events | 10 / 110 |
Outcome results
Primary
Number of Participants Progression-free at 18 Months
PSA progression is defined as a rise in PSA to \>4.0 ng/mL demonstrated twice in measurements taken two weeks apart.
Time frame: 18 months from the start of AA therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entire Study Population | Number of Participants Progression-free at 18 Months | 0 participants |
Secondary
Percent of Participants With Undetectable Prostate-specific Antigen (PSA) Response
Percent of participants who had undetectable PSA at 3 months on the initially assigned treatment arm (prior to crossing over).
Time frame: 3 months
Population: 105 participants had follow-up PSA information; those without a follow-up PSA were excluded from this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entire Study Population | Percent of Participants With Undetectable Prostate-specific Antigen (PSA) Response | 55 percentage of participants |
| Androgen Ablative (AA) Then AA Therapy + MDX-010 | Percent of Participants With Undetectable Prostate-specific Antigen (PSA) Response | 39 percentage of participants |