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Hormone Therapy and Ipilimumab in Treating Patients With Advanced Prostate Cancer

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00170157
First received: September 13, 2005
Last updated: April 6, 2017
Last verified: January 2017
  Purpose

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.


Condition Intervention Phase
Prostate Adenocarcinoma
Prostate Carcinoma
Recurrent Prostate Carcinoma
Stage III Prostate Cancer
Stage IV Prostate Cancer
Drug: Bicalutamide
Drug: Flutamide
Drug: Goserelin Acetate
Drug: Ipilimumab
Drug: Leuprolide Acetate
Other: Pharmacological Study
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase II Immunotherapeutic Trial: Combination Androgen Ablative Therapy and CTLA-4 Blockade as a Treatment for Advanced Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Number of Participants Progression-free at 18 Months [ Time Frame: 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 Outcome Measures:
  • Percent of Participants With Undetectable Prostate-specific Antigen (PSA) Response [ Time Frame: 3 months ]
    Percent of participants who had undetectable PSA at 3 months on the initially assigned treatment arm (prior to crossing over).


Enrollment: 112
Study Start Date: June 2004
Study Completion Date: June 2013
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Bicalutamide
Given orally
Other Names:
  • Casodex
  • Cosudex
  • ICI 176,334
  • ICI 176334
Drug: Flutamide
Given orally
Other Names:
  • 4'-Nitro-3'-trifluoromethylisobutyranilide
  • Apimid
  • Chimax
  • Drogenil
  • Euflex
  • Eulexin
  • Eulexine
  • Flucinom
  • Flucinome
  • Flugerel
  • Fluken
  • Flulem
  • FLUT
  • Fluta-Gry
  • Flutabene
  • Flutacan
  • Flutamex
  • Flutamin
  • Flutan
  • Flutaplex
  • Fugerel
  • Grisetin
  • Niftolid
  • Oncosal
  • Profamid
  • Prostacur
  • Prostadirex
  • Prostica
  • Prostogenat
  • SCH 13521
  • Tafenil
  • Tecnoflut
  • Testotard
Drug: Goserelin Acetate
Given SC
Other Names:
  • ZDX
  • Zoladex
Drug: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • MDX-010
  • MDX-CTLA4
  • Yervoy
Drug: Leuprolide Acetate
Given IM
Other Names:
  • A-43818
  • Abbott 43818
  • Abbott-43818
  • Carcinil
  • Depo-Eligard
  • Eligard
  • Enanton
  • Enantone
  • Enantone-Gyn
  • Ginecrin
  • LEUP
  • Leuplin
  • Leuprorelin Acetate
  • Lucrin
  • Lucrin Depot
  • Lupron
  • Lupron Depot
  • Lupron Depot-3 Month
  • Lupron Depot-4 Month
  • Lupron Depot-Ped
  • Procren
  • Procrin
  • Prostap
  • TAP-144
  • Trenantone
  • Uno-Enantone
  • Viadur
Other: Pharmacological Study
Correlative study
Active Comparator: Arm II
Patients receive AA therapy as in arm I. Patients may crossover to arm II in the case of disease progression.
Drug: Bicalutamide
Given orally
Other Names:
  • Casodex
  • Cosudex
  • ICI 176,334
  • ICI 176334
Drug: Flutamide
Given orally
Other Names:
  • 4'-Nitro-3'-trifluoromethylisobutyranilide
  • Apimid
  • Chimax
  • Drogenil
  • Euflex
  • Eulexin
  • Eulexine
  • Flucinom
  • Flucinome
  • Flugerel
  • Fluken
  • Flulem
  • FLUT
  • Fluta-Gry
  • Flutabene
  • Flutacan
  • Flutamex
  • Flutamin
  • Flutan
  • Flutaplex
  • Fugerel
  • Grisetin
  • Niftolid
  • Oncosal
  • Profamid
  • Prostacur
  • Prostadirex
  • Prostica
  • Prostogenat
  • SCH 13521
  • Tafenil
  • Tecnoflut
  • Testotard
Drug: Leuprolide Acetate
Given IM
Other Names:
  • A-43818
  • Abbott 43818
  • Abbott-43818
  • Carcinil
  • Depo-Eligard
  • Eligard
  • Enanton
  • Enantone
  • Enantone-Gyn
  • Ginecrin
  • LEUP
  • Leuplin
  • Leuprorelin Acetate
  • Lucrin
  • Lucrin Depot
  • Lupron
  • Lupron Depot
  • Lupron Depot-3 Month
  • Lupron Depot-4 Month
  • Lupron Depot-Ped
  • Procren
  • Procrin
  • Prostap
  • TAP-144
  • Trenantone
  • Uno-Enantone
  • Viadur
Other: Pharmacological Study
Correlative study

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00170157

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Principal Investigator: Eugene Kwon Mayo Clinic
  More Information

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00170157     History of Changes
Other Study ID Numbers: MC0253
NCI-2009-01214 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC0253 ( Other Identifier: Mayo Clinic )
P30CA015083 ( US NIH Grant/Contract Award Number )
Study First Received: September 13, 2005
Results First Received: May 3, 2013
Last Updated: April 6, 2017

Additional relevant MeSH terms:
Carcinoma
Prostatic Neoplasms
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Antibodies, Monoclonal
Bicalutamide
Flutamide
Leuprolide
Goserelin
Immunologic Factors
Physiological Effects of Drugs
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on May 24, 2017